Lung Infiltrates Research Articles

A Case Report of Isotretinoin: Acute Eosinophilic Pneumonia, A Rare Adverse Reaction

Abstract This is a case of acute eosinophilic pneumonia (AEP) in a 21-year-old woman with acne vulgaris who was treated with isotretinoin. During treatment, her blood tests showed normal results until the third month, when there was a slight increase in eosinophil count. In the fifth month of treatment, the patient presented to the pulmonology outpatient clinic with complaints of shortness of breath. Lung CT imaging revealed infiltration in both lungs characterized by ground glass opacities. AEP was diagnosed based on blood and imaging results. Isotretinoin therapy was terminated, and oral steroids were initiated, resulting in the improvement of the patient’s symptoms. The patient had no additional risk factors except for smoking, but she had not started or resumed smoking after quitting. This case report highlights the possibility of hypersensitivity pneumonitis following isotretinoin administration.

Chronic acid sphingomyelinase deficiency diagnosed in infancy/childhood in Polish patients: 2024 update.

Acid sphingomyelinase deficiency (ASMD) is an autosomal recessive lysosomal storage disease (LSD) associated with biallelic pathogenic variants in the sphingomyelin phosphodiesterase 1 (SMPD1) gene. The aim of this study was to provide the 2024 update on chronic visceral and neurovisceral ASMD diagnosed in the infancy/childhood in Polish patients. All the patients diagnosed in the pediatric age (0-18 years) with ASMD, both chronic neurovisceral and visceral type, and then systematically followed up, were enrolled into the study. A total number of 7 patients were enrolled into the study. Four patients were previously reported. Two patients were newly recognized with ASMD - 1 with chronic visceral and 1 with chronic neurovisceral ASMD. Splenomegaly was noted in all the patients while a mild liver enlargement was observed in 4 of 7 patients. All patients presented with decreased high-density lipoprotein cholesterol (HDL-C) and decreased serum 25-hydroxy-vitamin D concentration while almost all (6 of 7) with hypercholesterolemia. Cherry-red spot was observed in 5 of 7 patients, including 1 patient with neurovisceral type. Seven various SMPD1 gene variants were identified and missense variants were the most common types of genetic lesions, comprising 71% of all alleles. In all the screened patients, lyso-sphingomyelin (lyso-SM) in dried blood spot (DBS) was found elevated; however, the greater values were observed for patients with chronic neurovisceral type. Chronic acid sphingomyelinase deficiency (ASMD) is a slowly progressive disease. Pediatric ASMD is characterized by spleno-hepatomegaly, dyslipidemia (with decreased HDL-C as the most characteristic) and infiltrative (interstitial) lung disease. Both visceral and neurovisceral chronic ASMD patients could present with cherry-red spot. Both acid spingomyelinase activity and lyso-spingomyelin concentration in DBS should be regarded as a first-tier screening method into ASMD.

Metastatic Carcinosarcoma with a Sarcomatous Predominance?

Abstract Introduction/Objective Uterine carcinosarcoma (CS), also known as Malignant Mixed Müllerian Tumor, is a malignancy characterized by mixed epithelial and mesenchymal components. It is rare and aggressive, most frequently occurring in elderly, postmenopausal women with a median age of 65 years. CS has a tendency to metastasize with an overall poor prognosis. Fine needle aspiration can be useful in identifying metastatic disease, however, demonstration of both sarcomatous and carcinomatous components can be difficult. Methods/Case Report Our patient is a 68 year old female who was first diagnosed with endometrial carcinosarcoma on an endometrial biopsy in 2022. She subsequently underwent a total abdominal hysterectomy with radical dissection, bilateral salpingo-oophorectomy, upper vaginectomy, sentinel lymph node dissection as well as chemotherapy. Immunohistochemistry for MLH1, MSH2, MSH6 and PMS2 all showed intact nuclear expression. Remission was achieved for about a year, after which she was found to have a moderate right sided pleural effusion with right lower lung infiltrates. Also, a right upper lobe mass was reported on chest CT scan. Paracentesis was performed and cytology was consistent with predominantly atypical spindle cells accompanied by a mixed inflammatory infiltrate. Immunohistochemical stains were performed on the cell block, tumor cells were positive for smooth muscle actin, vimentin and negative for desmin, S-100, SOX-10, CD34, P63, TTF-1 and pancytokeratin. Cytology diagnosis was rendered as malignant cells present, consistent with metastatic CS. A subsequent lung mass core biopsy also confirmed the diagnosis. Results (if a Case Study enter NA) NA Conclusion The cytomorphological features in effusion samples from metastatic CS have the carcinomatous component readily identifiable, and only a minority of effusion samples show additional sarcomatous component. The exact diagnosis of CS may not be possible due to the absence of sarcomatous components. Alternatively, as we present in this rare case of metastatic CS, the sarcomatous component in the form of abundant atypical oval to spindle cells with hyperchromatic nuclei may be the only form of malignant cells present in the specimen. Careful morphological assessment of architectural patterns, a good past medical history, availability of cell blocks and immunohistochemistry are vital in providing an accurate diagnosis in such rare cases of metastatic CS.

Proteome Signature for Differential Diagnosis of Patients with Bilateral Lung Infiltrates

BackgroundThe differential diagnosis of bilateral lung infiltrates and prognosis prediction can be challenging for clinicians in the intensive care unit (ICU). We analyzed the proteome from bronchoalveolar lavage fluid (BALF) and determine their usefulness for evaluating the infectious causes and mortality associated with bilateral lung infiltrates.MethodsIn the ICU cohort, 136 patients with bilateral infiltrate on chest radiographs were selected, and bronchoscopy with bronchoalveolar lavage (BAL) was performed. Proteomics profiling of the exosomes in the BALF (n=20) was conducted to identify candidate protein biomarkers potentially associated with infection or mortality. The BAL samples (n=116) were used to measure the candidate biomarker levels.ResultsThe candidate biomarkers, CD20, CLIC4, SCFD1, and TAP1, were selected for the differential diagnosis of infection or mortality. The levels of CD20 were significantly elevated in patients with non-infectious causes compared to those with infectious causes (248.6±154.5versus177.6±150.9 ng·mL−1, p=0.014). The levels of CLIC4, SCFD1, and TAP1 did not differ between the two groups. As per the receiver operating characteristic analysis, CD20 was a significant predictor of non-infectious causes (area under curve, 0.668; 95% CI, 0.567–0.769; p=0.002; cut off value, 167.6 ng·mL−1; sensitivity, 74.1%; specificity, 63.2%). There were no significant differences in the concentrations of the biomarkers between survivors and non-survivors.ConclusionsOur results suggested that CD20 levels in BALF might be a useful biomarker for differentiating non-infectious and infectious diseases in patients with bilateral lung infiltrates.

Diagnosis of leukemic lung infiltration mimicking fungal infection by transbronchial lung cryobiopsy: the first case report

BackgroundWe here report the first case of leukemic lung infiltration diagnosed by transbronchial lung cryobiopsy (TBLC). TBLC is likely to be a superior method to transbronchial forceps biopsy because TBLC can get larger specimens, resulting in a higher chance of containing the leukemic cells infiltrated tissues. TBLC is generally considered a superior diagnostic method compared to transbronchial lung forceps biopsy (TBLB) because it utilizes cryotechnology to obtain larger specimens, increasing the likelihood of capturing tissues infiltrated with leukemic cells.Case presentationA 69-year-old male patient with acute myeloid leukemia presented with a fever. His initial chest CT scans revealed consolidative lesions, raising suspicion of fungal infection such as angioinvasive aspergillosis or mucormycosis. TBLC and TBLB were conducted to achieve a precise diagnosis, and eventually, leukemic lung infiltration was identified exclusively in the tissues obtained from TBLC. Two cycles of chemotherapy was administrated to patient, showing improvements in symptoms and chest CT findings.ConclusionsTBLC has greater potential as a differential diagnostic method for pulmonary lesions than TBLB in leukemia patients facing therapeutic challenges due to its higher diagnostic yield.

Patients with influenza admitted to a tertiary-care hospital in Riyadh between 2018 and 2022: characteristics, outcomes and factors associated with ICU admission and mortality

BackgroundInfluenza is a common cause of hospital admissions globally with regional variations in epidemiology and clinical profile. We evaluated the characteristics and outcomes of patients with influenza admitted to a tertiary-care center in Riyadh, Saudi Arabia.MethodsThis was a retrospective cohort of adult patients admitted with polymerase chain reaction-confirmed influenza to King Abdulaziz Medical City-Riyadh between January 1, 2018, and May 31, 2022. We compared patients who required intensive care unit (ICU) admission to those who did not and performed multivariable logistic regression to assess the predictors of ICU admission and hospital mortality.ResultsDuring the study period, 675 adult patients were hospitalized with influenza (median age 68.0 years, females 53.8%, hypertension 59.9%, diabetes 55.1%, and chronic respiratory disease 31.1%). Most admissions (83.0%) were in the colder months (October to March) in Riyadh with inter-seasonal cases even in the summertime (June to August). Influenza A was responsible for 79.0% of cases, with H3N2 and H1N1 subtypes commonly circulating in the study period. Respiratory viral coinfection occurred in 12 patients (1.8%) and bacterial coinfection in 42 patients (17.4%). 151 patients (22.4%) required ICU admission, of which 62.3% received vasopressors and 48.0% mechanical ventilation. Risk factors for ICU admission were younger age, hypertension, bilateral lung infiltrates on chest X-ray, and Pneumonia Severity Index. The overall hospital mortality was 7.4% (22.5% for ICU patients, p < 0.0001). Mortality was 45.0% in patients with bacterial coinfection, 30.9% in those requiring vasopressors, and 29.2% in those who received mechanical ventilation. Female sex (odds ratio [OR], 2.096; 95% confidence interval [CI] 1.070, 4.104), ischemic heart disease (OR, 3.053; 95% CI 1.457, 6.394), immunosuppressed state (OR, 7.102; 95% CI 1.803, 27.975), Pneumonia Severity Index (OR, 1.029; 95% CI, 1.017, 1.041), leukocyte count and serum lactate level (OR, 1.394; 95% CI, 1.163, 1.671) were independently associated with hospital mortality.ConclusionsInfluenza followed a seasonal pattern in Saudi Arabia, with H3N2 and H1N1 being the predominant circulating strains during the study period. ICU admission was required for > 20%. Female sex, high Pneumonia Severity Index, ischemic heart disease, and immunosuppressed state were associated with increased mortality.

HMGB1 derived from lung epithelial cells after cobalt nanoparticle exposure promotes the activation of lung fibroblasts

We have previously demonstrated that exposure to cobalt nanoparticles (Nano-Co) caused extensive interstitial fibrosis and inflammatory cell infiltration in mouse lungs. However, the underlying mechanisms of Nano-Co-induced pulmonary fibrosis remain unclear. In this study, we investigated the role of high-mobility group box 1 (HMGB1) in the epithelial cell-fibroblast crosstalk in Nano-Co-induced pulmonary fibrosis. Our results showed that Nano-Co exposure caused remarkable production and release of HMGB1, as well as nuclear accumulation of HIF-1α in human bronchial epithelial cells (BEAS-2B) in a dose- and a time-dependent manner. Pretreatment with CAY10585, an inhibitor against HIF-1α, significantly blocked the overexpression of HMGB1 in cell lysate and the release of HMGB1 in the supernatant of BEAS-2B cells induced by Nano-Co exposure, indicating that Nano-Co exposure induces HIF-1α-dependent HMGB1 overexpression and release. In addition, treatment of lung fibroblasts (MRC-5) with conditioned media from Nano-Co-exposed BEAS-2B cells caused increased RAGE expression, MAPK signaling activation, and enhanced expression of fibrosis-associated proteins, such as fibronectin, collagen 1, and α-SMA. However, conditioned media from Nano-Co-exposed BEAS-2B cells with HMGB1 knockdown had no effects on the activation of MRC-5 fibroblasts. Finally, inhibition of ERK1/2, p38, and JNK all abolished MRC-5 activation induced by conditioned media from Nano-Co-exposed BEAS-2B cells, suggesting that MAPK signaling might be a key downstream signal of HMGB1/RAGE to promote MRC-5 fibroblast activation. These findings have important implications for understanding the pro-fibrotic potential of Nano-Co.

CLINICAL SPECTRUM OF DISEASE IN NEONATES BORN TO MOTHERS WITH COVID-19 IN A TERTIARY CARE HOSPITAL

COVID-19 infection during pregnancy presents potential risks to neonates, yet the full clinical spectrum in newborns born to COVID-19-positive mothers remains under investigation. Understanding the clinical outcomes in these neonates is essential for guiding management and care. Objective: To study the spectrum of clinical presentations in neonates born to mothers who tested positive for COVID-19. Methods: This prospective cross-sectional study was conducted at the Department of Pediatrics, Shifa International Hospital, from April 1, 2020, to April 30, 2021. All neonates born to COVID-19-positive mothers were included in the study and followed daily during their hospital stay. After obtaining parental consent, nasopharyngeal swabs were taken from the neonates for SARS-CoV-2 PCR testing at 24-48 hours of age. After discharge, follow-up calls were made between days 7-14. Data were entered into a predesigned proforma and analyzed using SPSS version 23. Results: A total of 82 neonates were enrolled. Approximately half were born at term, with a mean weight of &gt;2500 grams. Forty-five neonates (53%) underwent SARS-CoV-2 PCR testing within 48 hours of age; all were negative. Sixty-one neonates (74%) were shifted to the mother’s care, while 25% required admission to the neonatal intensive care unit (NICU). The most common reasons for NICU admission included respiratory distress (15%), prematurity (6%), and lethargy (5%). Radiological findings included ground-glass appearance in five neonates (6%) and lung consolidation or infiltrates in two (3%). Hematological and biochemical abnormalities included leukocytosis (7%), leucopenia (3.6%), anemia (1.2%), metabolic acidosis (6%), and respiratory acidosis (3.6%). Most neonates (78.6%) received routine care and were fed breast milk. Fourteen neonates (16.7%) required respiratory support, with 13% needing mechanical ventilation. Complications included pneumonia (7%) and respiratory failure (9%). NICU stay varied, with 11 neonates (13%) staying less than 48 hours and 10 (12%) requiring a more extended stay. Four neonates (5%) died due to multiorgan complications. Conclusion: The majority of neonates born to COVID-19-positive mothers remained asymptomatic. However, symptomatic neonates were at risk of serious complications, requiring close monitoring and management, particularly in those with additional risk factors.

The angiotensin-(1-7)/MasR axis improves pneumonia caused by Pseudomonas aeruginosa: Extending the therapeutic window for antibiotic therapy.

Pseudomonas aeruginosa is a frequent cause of antimicrobial-resistant hospital-acquired pneumonia, especially in critically ill patients. Inflammation triggered by P. aeruginosa infection is necessary for bacterial clearance but must be spatially and temporally regulated to prevent further tissue damage and bacterial dissemination. Emerging data have shed light on the pro-resolving actions of angiotensin-(1-7) [Ang-(1-7)] signaling through the G protein-coupled receptor Mas (MasR) during infections. Herein, we investigated the role of the Ang-(1-7)/Mas axis in pneumonia caused by P. aeruginosa by using genetic and pharmacological approach and found that Mas receptor-deficient animals developed a more severe form of pneumonia showing higher neutrophilic infiltration into the airways, bacterial load, cytokines, and chemokines production and more severe pulmonary damage. Conversely, treatment of pseudomonas-infected mice with Ang-(1-7) was able to decrease neutrophilic infiltration in airways and lungs, local and systemic levels of pro-inflammatory cytokines and chemokines, and increase the efferocytosis rates, mitigating lung damage/dysfunction caused by infection. Notably, the therapeutic association of Ang-(1-7) with antibiotics improved the survival rates of mice subjected to lethal inoculum of P. aeruginosa, extending the therapeutic window for imipenem. Mechanistically, Ang-(1-7) increased phagocytosis of bacteria by neutrophils and macrophages to accelerate pathogen clearance. Altogether, harnessing the Ang-(1-7) pathway during infection is a potential strategy for the development of host-directed therapies to promote mechanisms of resistance and resilience to pneumonia.

Hot Dab Associated Pneumonitis - a case report

BackgroundDabbing is recently getting popular among young adults. It is a new method of using the most active form of marijuana where large amounts of concentrated tetrahydrocannabinol are inhaled. Tetrahydrocannabinol is associated with a feeling of ‘High’ which makes the user feel joyous and relaxed. With increasing use of such techniques, dabbing becomes an important differential for evaluation of acute respiratory failure with pneumonitis especially in the adult population.Case presentationA Fifty-one years old Caucasian man presented to the hospital with chest pressure and shortness of breath. The patient was noted to be hypoxic, desaturating down to 82–83% on nasal cannula oxygen. Imaging revealed bilateral lung infiltrates. Patient was started on high flow oxygen, broad spectrum antibiotics and intravenous corticosteroids. The patient gradually improved and was able to come off oxygen completely. He was discharged home on prednisone taper.ConclusionsDabbing is a newer technique which has been gaining popularity for marijuana usage. With the legalization of marijuana, newer techniques are getting popular. Our case report emphasizes the importance of keeping dabbing as a differential when a patient presents with respiratory failure and has concerns for pneumonitis. Patients might not reveal until specifically asked about their practices.

IL-10 deficiency aggravates cell senescence and accelerates BLM-induced pulmonary fibrosis in aged mice via PTEN/AKT/ERK pathway

BackgroundPulmonary fibrosis (PF) is an aging-related progressive lung disorder. The aged lung undergoes functional and structural changes termed immunosenescence and inflammaging, which facilitate the occurrence of fibrosis. Interleukin-10 (IL-10) is a potent anti-inflammatory and immunoregulatory cytokine, yet it remains unclear how IL-10 deficiency-induced immunosenescence participates in the development of PF.MethodsFirstly we evaluated the susceptibility to fibrosis and IL-10 expression in aged mice. Then 13-month-old wild-type (WT) and IL-10 knockout (KO) mice were subjected to bleomycin(BLM) and analyzed senescence-related markers by PCR, western blot and immunohistochemistry staining of p16, p21, p53, as well as DHE and SA-β-gal staining. We further compared 18-month-old WT mice with 13-month-old IL-10KO mice to assess aging-associated cell senescence and inflamation infiltration in both lung and BALF. Moreover, proliferation and apoptosis of alveolar type 2 cells(AT2) were evaluated by FCM, immunofluorescence, TUNEL staining, and TEM analysis. Recombinant IL-10 (rIL-10) was also administered intratracheally to evaluate its therapeutic potential and related mechanism. For the in vitro experiments, 10-week-old naïve pramily lung fibroblasts(PLFs) were treated with the culture medium of 13-month PLFs derived from WT, IL-10KO, or IL-10KO + rIL-10 respectively, and examined the secretion of senescence-associated secretory phenotype (SASP) factors and related pathways.ResultsThe aged mice displayed increased susceptibility to fibrosis and decreased IL-10 expression. The 13-month-old IL-10KO mice exhibited significant exacerbation of cell senescence compared to their contemporary WT mice, and even more severe epithelial-mesenchymal transition (EMT) than that of 18 month WT mice. These IL-10 deficient mice showed heightened inflammatory responses and accelerated PF progression. Intratracheal administration of rIL-10 reduced lung CD45 + cell infiltration by 15%, including a 6% reduction in granulocytes and a 10% reduction in macrophages, and increased the proportion of AT2 cells by approximately 8%. Additionally, rIL-10 significantly decreased α-SMA and collagen deposition, and reduced the expression of senescence proteins p16 and p21 by 50% in these mice. In vitro analysis revealed that conditioned media from IL-10 deficient mice promoted SASP secretion and upregulated senescence genes in naïve lung fibroblasts, which was mitigated by rIL-10 treatment. Mechanistically, rIL-10 inhibited TGF-β-Smad2/3 and PTEN/PI3K/AKT/ERK pathways, thereby suppressing senescence and fibrosis-related proteins.ConclusionsIL-10 deficiency in aged mice leads to accelerated cell senescence and exacerbated fibrosis, with IL-10KO-PLFs displaying increased SASP secretion. Recombinant IL-10 treatment effectively mitigates these effects, suggesting its potential as a therapeutic target for PF.Graphical

MIP3α-Rel Mtb intranasal DNA vaccination induces reactive T-cell infiltration into the lungs in mice and macaques.

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), is the leading cause of mortality due to a single infectious organism. While generally curable, TB requires a lengthy and complex antibiotic regimen, due in large part to bacteria that can shift to a persistent state in the presence of antibiotic pressure. Rel Mtb is the primary enzyme regulating the stringent response, which contributes to the metabolic shift of Mtb to a persistent state. Targeting Rel Mtb with a vaccine to eliminate persistent bacteria through the induction of Rel Mtb -specific T-cell immunity in combination with antibiotics to kill dividing bacteria has shown promise in model systems. In a mouse model of Mtb infection, a vaccine created by genetically fusing rel Mtb to the chemokine macrophage inflammatory protein 3α ( MIP3 α), a ligand for the CC chemokine receptor type 6 (CCR6) present on immature dendritic cells, has been shown to enhance T-cell responses and accelerate eradication of infection in mouse models compared to a vaccine lacking the chemokine component. In this study, immunogenicity studies in the mouse and rhesus macaque models provide evidence that intranasal administrations of the DNA form of the MipRel vaccine led to enhanced lung infiltration of T cells after a series of immunizations. Furthermore, despite similar T-cell immunity seen in PBMCs between MipRel and Rel vaccinations, lung and bronchoalveolar lavage cell samples are more enriched for cytokine-secreting T cells in MipRel groups compared to Rel groups. We conclude that intranasal immunization with a MIP-3α fusion vaccine represents a novel strategy for use of a simple DNA vaccine formulation to elicit T-cell immune responses within the respiratory tract. That this formulation is immunogenic in a non-human primate model historically viewed as poorly responsive to DNA vaccines indicates the potential for clinical application in the treatment of Mtb infection, with possible application to other respiratory pathogens. Future studies will further characterize the protective effect of this vaccination platform.

Enhancement of Semantic Segmentation by Image‐Level Fine‐Tuning to Overcome Image Pattern Imbalance in HRCT of Diffuse Infiltrative Lung Diseases

ABSTRACTDiagnosing diffuse infiltrative lung diseases (DILD) using high‐resolution computed tomography (HRCT) is challenging, even for expert radiologists, due to the complex and variable image patterns. Moreover, the imbalances among the six key DILD‐related patterns—normal, ground‐glass opacity, reticular opacity, honeycombing, emphysema, and consolidation—further complicate accurate segmentation and diagnosis. This study presents an enhanced U‐Net‐based segmentation technique aimed at addressing these challenges. The primary contribution of our work is the fine‐tuning of the U‐Net model using image‐level labels from 92 HRCT images that include various types of DILDs, such as cryptogenic organizing pneumonia, usual interstitial pneumonia, and nonspecific interstitial pneumonia. This approach helps to correct the imbalance among image patterns, improving the model's ability to accurately differentiate between them. By employing semantic lung segmentation and patch‐level machine learning, the fine‐tuned model demonstrated improved agreement with radiologists' evaluations compared to conventional methods. This suggests a significant enhancement in both segmentation accuracy and inter‐observer consistency. In conclusion, the fine‐tuned U‐Net model offers a more reliable tool for HRCT image segmentation, making it a valuable imaging biomarker for guiding treatment decisions in patients with DILD. By addressing the issue of pattern imbalances, our model significantly improves the accuracy of DILD diagnosis, which is crucial for effective patient care.

A Retrospective Study: Evaluating the Impact of the COVID-19 Pandemic on Inflammatory Markers in Hospitalized Patients.

The COVID-19 pandemic has had a significant impact globally, and understanding the relationship between inflammatory markers and disease progression is crucial for effective management. This retrospective study aimed to examine the association between various inflammatory markers, such as C-reactive protein (CRP), the erythrocyte sedimentation rate (ESR), lactate dehydrogenase (LDH), D-dimer, ferritin, and procalcitonin (PCT), and the characteristics of disease progression and outcomes in individuals affected by COVID-19. This study collected raw data from 470 patients who tested positive for SARS-CoV-2 using RT-PCR. The logistic regression analysis revealed that elevated LDH levels were associated with male gender, ICU admission, low oxygen saturation (O2 < 93%), the need for mechanical ventilation, death, and the presence of lung infiltrates. Higher D-dimer levels were associated with older age, diabetes mellitus, cardiac disease, and low oxygen saturation. Ferritin levels were significantly associated with older age, ICU admission, low oxygen saturation, mechanical ventilation, and lung infiltrates. In contrast, CRP was only significant regarding lung infiltrates and procalcitonin levels were not significantly associated with any of the examined factors. This study highlights the importance of monitoring key inflammatory markers, such as LDH, D-dimer, and ferritin, as they are significantly associated with the severity of COVID-19 illness. These findings can inform clinical decision-making and guide the development of targeted interventions to improve patient outcomes.

The Role of Early Hemoadsorption in Severe COVID-19 Treatment: A Pilot Randomized Controlled Trial

Introduction: Hemoadsorption, an extracorporeal apheresis technique, is reportedly used in severe COVID-19 patients. However, limited evidence from randomized clinical trials supports this practice. Methods: In this single-center study, severe COVID-19 patients requiring ICU admission were randomly assigned (1:1) to receive HA-330 hemoadsorption in combination with standard treatment or standard therapy alone. Both groups received tocilizumab intravenously if their clinical conditions worsened within 24–48 h. The primary outcome was mortality from any cause within 28 days after randomization. Secondary outcomes included mechanical ventilator-free days, daily C-reactive protein levels, oxygenation (defined by PaO2/FiO2 ratio), daily sequential organ failure assessment score, and severity score of lung infiltration on chest X-rays (CXR RALE score). Results: A total of 28 patients underwent randomization, with 14 (50%) receiving HA-330 hemoadsorption. Only 9 out of 14 patients (64.3%) in the control group experienced clinical worsening and were subsequently administered intravenous tocilizumab. At 28 days, the mortality rate was significantly lower in the intervention group (28.57% vs. 78.57%, p = 0.021), with a hazard ratio of death of 0.26 (95% CI = 0.08–0.81; p = 0.021). All of secondary outcomes were comparable in both groups. Conclusion: Based on our pilot randomized trial, the early application of HA-330 hemoadsorption in patients with severe COVID-19 may establish a favorable outcome in term of mortality. These data provide the initial proof of concept for conducting a large-scale study in the future.

ImmunoPET imaging of LAG-3 expression in tumor microenvironment with 68Ga-labelled cyclic peptides tracers: from bench to bedside

BackgroundLymphocyte activation gene 3 (LAG-3) has been considered as the next generation of immune checkpoint and a promising prognostic biomarker of immunotherapy. As with programmed cell death protein-1/programmed death-ligand 1...

Skin Rash with Acute Respiratory Distress Syndrome in Chronic Miliary Tuberculosis: The Role of HRCT Thorax and Bronchoscopy as Diagnostic Tools

Pulmonary tuberculosis (TB) is a leading cause of mortality and morbidity in India, presenting with diverse clinical and radiological manifestations such as consolidation, cavitation, lymphadenopathy, pleural effusion, miliary TB, and endobronchial TB. While acute miliary TB presenting as Acute respiratory distress syndrome (ARDS) is documented, the association with a skin rash mimicking viral exanthematous fever is not. This case report describes the case of a 41-year-old male patient with acute dyspnea, a maculopapular rash, and lung infiltrates on chest radiograph, initially diagnosed with acute hypoxic respiratory failure and later confirmed as ARDS. High-resolution computed tomography (HRCT) thorax revealed consolidation with nodules and a characteristic butterfly pattern sparing the apices and bases. Bronchoscopy confirmed TB etiology through MTB genome in BAL samples. The patient improved significantly with intravenous antibiotics, steroids, and HFNC, leading to a documented cure after 6 months of anti-tuberculosis treatment. This report highlights the importance of considering TB in cases with nodular consolidation and positive limiting signs and recommends ICU bronchoscopy as a reliable diagnostic tool. The Kigali modification for ARDS definition was instrumental in managing this case. Use of Kigali modification for defining ARDS in resource limited setting guided management in our case.

An antibody to IL-1 receptor 7 protects mice from LPS-induced tissue and systemic inflammation.

Interleukin-18 (IL-18), a pro-inflammatory cytokine belonging to the IL-1 Family, is a key mediator ofautoinflammatory diseases associated with the development of macrophage activation syndrome (MAS).High levels of IL-18 correlate with MAS and COVID-19 severity and mortality, particularly in COVID-19patients with MAS. As an inflammation inducer, IL-18 binds its receptor IL-1 Receptor 5 (IL-1R5), leadingto the recruitment of the co-receptor, IL-1 Receptor 7 (IL-1R7). This heterotrimeric complex subsequentlyinitiates downstream signaling, resulting in local and systemic inflammation. We reported earlier the development of a novel humanized monoclonal anti-human IL-1R7 antibody whichspecifically blocks the activity of human IL-18 and its inflammatory signaling in human cell and wholeblood cultures. In the current study, we further explored the strategy of blocking IL-1R7 inhyperinflammation in vivo using animal models. We first identified an anti-mouse IL-1R7 antibody that significantly suppressed mouse IL-18 andlipopolysaccharide (LPS)-induced IFNg production in mouse splenocyte and peritoneal cell cultures. Whenapplied in vivo, the antibody reduced Propionibacterium acnes and LPS-induced liver injury and protectedmice from tissue and systemic hyperinflammation. Importantly, anti-IL-1R7 significantly inhibited plasma,liver cell and spleen cell IFNg production. Also, anti-IL-1R7 downregulated plasma TNFa, IL-6, IL-1b,MIP-2 production and the production of the liver enzyme ALT. In parallel, anti-IL-1R7 suppressed LPSinducedinflammatory cell infiltration in lungs and inhibited the subsequent IFNg production andinflammation in mice when assessed using an acute lung injury model. Altogether, our data suggest that blocking IL-1R7 represents a potential therapeutic strategy to specificallymodulate IL-18-mediated hyperinflammation, warranting further investigation of its clinical application intreating IL-18-mediated diseases, including MAS and COVID-19.

Pulmonary presentation and coil marcation of dirofilaria lung coin nodes - case report.

Clinicians face significant diagnostic challenges when dealing with nodal lesions of the lung. The majority of lung nodules are benign; however, asignificant number can be cancerous. Dirofilaria infestation should also be considered in the differential diagnosis of nodal lung lesions. Most patients with Dirofilaria infestation are asymptomatic. To determine the etiology of nodal lung infiltrations, procedures like radiological imaging, bronchoscopy, endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA), transthoracic biopsy (TTB), tumor markers, nonspecific serological tests, or surgical removal of the lung coin lesions can be performed. Coil marking of the smaller lung lesions under computed tomography (CT) guidance is ahelpful tool in determining the position and localization of the nodal lung lesions. Video-assisted thoracoscopic surgery (VATS) or robot-assisted thoracoscopic surgery (RATS) wedge resection is adiagnostic and therapeutic method of choice. No additional treatment of Dirofilaria other than wedge resection of the lung is necessary.

Red flags for clinical suspicion of eosinophilic granulomatosis with polyangiitis (EGPA)

BackgroundEosinophilic granulomatosis with polyangiitis (EGPA), is a rare ANCA-associated systemic vasculitis. Its overlapping features with other vasculitic or eosinophilic diseases, and the wide and heterogeneous range of clinical manifestations, often result in a delay to diagnosis. ObjectiveTo identify red flags that raise a suspicion of EGPA to prompt diagnostic testing and to present an evidence-based clinical checklist tool for use in routine clinical practice. MethodsSystematic literature review and expert consensus to identify a list of red flags based on clinical judgement. GRADE applied to generate a strength of recommendation for each red flag and to develop a checklist tool. Results86 studies were included. 40 red flags were identified as relevant to raise a suspicion of EGPA and assessed by the experts as being clinically significant. Experts agreed that a diagnosis of EGPA should be considered in a patient aged ≥6 years with a blood eosinophil level >1000 cells/µL if untreated and >500 cells/µL if previously treated with any medication likely to have altered the blood eosinophil count. The presence of asthma and/or nasal polyposis should reinforce a suspicion of EGPA. Red flags of asthma, lung infiltrates, pericarditis, cardiomyopathy, polyneuropathy, biopsy with inflammatory eosinophilic infiltrates, palpable purpura, digital ischaemia and ANCA positivity, usually anti-myeloperoxidase, among others, were identified. ConclusionThe identification of a comprehensive set of red flags could be used to raise a suspicion of EGPA in patients with eosinophilia, providing clinicians with an evidence-based checklist tool that can be integrated into their practice.