Lung Infiltrates Research Articles

Prolonged Corticosteroid Use in the Treatment of Tuberculous Meningoencephalitis: A Case Report

Tuberculous meningoencephalitis is a rare manifestation of Mycobacterium tuberculosis (Mtb), with the most severe form and highest mortality. It can cause multiple complications, and treatment is difficult, as drugs cannot properly diffuse through the haemato-encephalitic barrier. We reported the case of a 17-year-old female patient who was admitted to the emergency room department with a fever for previous two weeks (up to 39 °C), dizziness, difficulty walking, and weight loss. Magnetic resonance imaging indicated possible meningoencephalitis, and a CT scan of the lungs visualised miliary infiltrates in both lungs. After repeated tests, Mtb DNA was found in the bronchial wash, cerebrospinal fluid, faeces, and urine via an Xpert/Rif Ultra test. Treatment was started with isoniazid, rifampicin, ethambutol, pyrazinamide, and corticosteroids as well. Although treatment was initiated within the first few days in the hospital, a reduction in glucocorticoid dosage worsened the patient’s neurological state, making treatment even more challenging. Prolonged use of glucocorticoids led to an improvement in the stage of the condition. Further, over time, the patient’s condition improved. Pulmonary infiltrations were not found after 2.5 months of starting therapy. Conclusions: Timely treatment is crucial for improving the prognosis of patients with miliary tuberculosis and tuberculous meningoencephalitis. Prompt recognition of symptoms and accurate diagnosis are essential to initiate effective treatment strategies. In this patient’s case, prolonged use of corticosteroids reduced neurologic complications, and ongoing treatment gradually improved the patient’s condition.

Double Outlet Right Ventricle: A Rare Finding in a 15-Month-Old Female With Failure to Thrive.

Double outlet right ventricle (DORV) is a rare congenital heart defect where both the aorta and pulmonary artery originate from the right ventricle, often accompanied by additional cardiac anomalies to mitigate circulatory imbalance, though such compensations usually fail. We report a 15-month-old infant with recurrent respiratory infections and poor weight gain, referred for computed tomography angiography. Physical examination showed a small, non-syndromic infant with pallor, tachypnea, irritability, and finger clubbing. Initial imaging revealed cardiomegaly and lung infiltrates; echocardiography and computed tomography angiography confirmed additional intracardiac defects of double superior vena cavae, a hypoplastic aortic arch, hypertrophic right ventricular wall, and a patent ductus arteriosus. Corrective surgery was delayed due to respiratory complications. This case emphasizes the critical need to consider cardiac pathology in pediatric patients with recurrent respiratory symptoms, as untreated DORV can lead to high mortality.

Inflammatory myopathy with abundant macrophage [IMAM]: Systemic analysis and pathological approach to distinguish it from dermatomyositis

Background: Inflammatory myopathy with abundant macrophage [IMAM] is marked by macrophage infiltration and muscle fibers damage, resembling dermatomyositis [DM] but with unique pathology. Its mechanism remains unclear. Our study focused on exploring the clinicopathological characteristics, underlying pathogenic mechanisms, and the challenges in diagnosing and managing IMAM. Methods: A systematic analysis of medical literature databases (Pub-med, Cochrane, Scopus, Google Scholar) was performed using the term “IMAM,” excluding studies on other inflammatory myopathies [IMs]. Selected studies were independently assessed with the Newcastle-Ottawa Scale, and quantitative data underwent inter-statistical analysis, descriptive and odds ratio, to identify relevant findings. Results: Eight studies, including 49 IMAM cases from 2003 to 2024, were analyzed. Five were case reports, and three were cross-sectional studies. IMAM showed no age or sex predilection. Common symptoms included proximal muscle weakness, pain, and fatigue, with atypical DM-like skin features in 65% of cases. Other association included hemophagocytosis, cutaneous panniculitis, and interstitial lung infiltration. Histologically, all cases showed myonecrosis infiltrated with CD68+ macrophages. Scattered CD3+ and CD4+ T-cells expressing IL-10 with no or rare CD8+ T-cells were identified. MAC deposition was limited to necrotic fibers, and perifascicular atrophy was absent in all cases. Anti-PL-7 and anti-U1 RNP antibodies were detected in 4% of cases. Elevated TNFα and IFN-γ levels, with low STAT1 and STAT6, were observed. Genetic analysis revealed MEFV polymorphisms in 7 cases and a TNFRSF1A mutation [C43R] in single case. Treatment involved steroids, with or without immunotherapy or chemotherapy, leading to remission and recovery in 43.7% of cases. Conclusion: IMAM is a distinct type of IMs that requires muscle biopsy for diagnosis as myositis antibody and cytokine tests are usually insensitive.

Successful utilization of plasma exchange and corticosteroids in the management of thrombotic microangiopathy and acute respiratory distress syndrome secondary to leptospirosis-a case report

<p><strong>Background:</strong> Leptospirosis, a zoonotic infection caused by Leptospira bacteria, presents with symptoms ranging from mild flu-like signs to severe multiorgan failure. A rare but serious complication of leptospirosis is thrombotic microangiopathy (TMA). This case report discusses the treatment of a 52-year-old female with leptospirosis complicated by TMA, highlighting the effectiveness of plasma exchange and corticosteroids in her recovery.<br /><strong>Case Presentation:</strong> A 52-year-old female presented with a five-day history of fever and progressive shortness of breath. Upon<br />admission, she had tachypnoea, a partial pressure of oxygen in arterial blood (PaO2) to the fraction of inspiratory oxygen<br />concentration (FiO2) ratio of 61, and bilateral lung infiltrates, requiring invasive mechanical ventilation and prone positioning.<br />Laboratory tests revealed anemia, thrombocytopenia, schistocytes, and elevated lactate dehydrogenase, suggesting TMA. The<br />patient also showed elevated liver enzymes and signs of a potential diagnosis of thrombotic thrombocytopenic purpura, though serological tests for tropical infections, including leptospirosis, were initially negative. The patient was treated with plasma exchange and corticosteroids, leading to improvements in her hematological parameters and acute respiratory distress syndrome (ARDS). However, she developed unexplained blood pressure and heart rate fluctuations, and electroencephalogram confirmed focal seizures, which were treated with levetiracetam and propofol. Subsequent serological testing confirmed leptospirosis with positive Immunoglobulin M antibodies and Leptospira polymerase chain reaction testing. The patient was treated with doxycycline and ceftriaxone, resulting in significant improvement, successful extubation, and eventual discharge.<br /><strong>Conclusion:</strong> This case highlights the challenges of managing leptospirosis complicated by TMA and severe ARDS. Plasma<br />exchange and corticosteroids were essential in the patient’s recovery. The initial delay in diagnosis due to negative serological<br />tests underscores the importance of maintaining a high index of suspicion for leptospirosis in severe tropical illness cases with<br />TMA. The patient’s positive response to treatment, including resolution of seizures and hemodynamic instability, demonstrates<br />the value of prompt and targeted interventions. The case emphasizes the need for a multidisciplinary approach in managing<br />complex leptospirosis cases with severe complications.</p>

Prevalence of multidrug-resistant gram-negative bacilli (MDR-GNB) in hospital-acquired and ventilator-associated pneumonia: A comparative study from a tertiary care center, Gujarat

Antibiotic resistance poses a formidable challenge to global healthcare, with Gram-negative bacteria emerging as a primary concern. Multidrug-resistant Gram-negative bacilli (MDR-GNB) have become a significant cause of nosocomial infections, particularly pneumonia, complicate therapy, and have a detrimental impact on patients’ outcomes. This study aims to investigate the etiology, risk factors, and antibiotic resistance patterns associated with Gram-negative bacilli (GNB) isolated from nosocomial pneumonia cases.This prospective cross-sectional study was conducted at the Microbiology laboratory of a tertiary care Hospital in Gujarat. Patients hospitalized for >48 hours with new lung infiltrates and at least two of the following clinical features: fever, leukocytosis/leukopenia, purulent secretions, or decreased oxygenation were included. The study was initiated after the ethical approval. Patient demographic and clinical details were noted in the preformed questionnaire. A total of 64 specimens [Sputum (n= 28) and Endotracheal aspirate (ET, n=36)] were cultured on MacConkey’s agar and Blood agar and further species identification with Antimicrobial Susceptibility Pattern was done by automated Vitek-2 compact system. Ventilator-associated Pneumonia (VAP) was found in 14.6% of infected patients, with male predominance and common in the 30-50 years age group. Out of them, 72% were mainly associated with late-onset. Overall, the major isolates were (20/64, 31%), followed by (19/64, 29.6%) and (17/64, 26.5%) both as solitary and mixed infections.76% strains of and 85% of strains were resistant to carbapenems and 93.3% of were resistant to cephalosporins and carbapenems. strains were 100% resistant to carbapenems. The study recommends effective Infection control practices and strong antibiotic stewardship programs to reduce the morbidity and mortality of nosocomial pneumonia.

Cord blood T regulatory cells synergize with ruxolitinib to improve GVHD outcomes.

Adoptive therapy with umbilical cord blood (UCB) T-regulatory (Treg) cells can prevent graft vs. host disease (GVHD). We hypothesize that UCB Tregs can treat GVHD and synergize with ruxolitinib, Jak2 inhibitor, to improve outcomes. UCB Treg potency and efficacy was examined using cell suppression assay and xenogeneic GVHD model, respectively. Ruxolitinib was fed continuously in presence or absence of CellTraceViolet tagged UCB Tregs on days +4, +7, +11, +18. Mice were followed for survival, GVHD score, hematology parameters and inflammation. Addition of ruxolitinib to UCB Tregs exerted synergistic suppressor function in vitro and improved persistence of UCB Tregs in vivo. Lower GVHD score, improved survival, increased hemoglobin level and platelet count, decreased inflammatory cytokines and decrease in CD3+ T cell lung infiltrate was observed in UCB Tregs+ruxolitinib recipients. UCB Treg+Ruxolitinib combination improves outcomes in xenogeneic GVHD and should be explored in a clinical setting.

Efficacy of Vyaghriharitaki Avaleha in the management of Vataja Kasa w.s.r. to Pulmonary Eosinophilia - An Open Label Randomized Controlled Clinical Trial

Background: Vataja Kasa (cough caused by Vata Dosha) occurs due to Pranavaha Srotodushti (causes of deformity in channels of respiratory system) characterized by dry paroxysmal cough that resembles Pulmonary eosinophilia (PE) with an elevated Absolute eosinophilic count (AEC) and eosinophilic lung infiltration. Vyaghriharitaki Avaleha is mentioned in Ayurveda classics under the context of Kasa (cough). The current study was carried out to assess its efficacy based on literary indications and the need for more potent medications to treat Vataja Kasa. Aim: Evaluation of the efficacy of Vyaghriharitaki Avaleha in the management of Vataja Kasa. Materials and Methods: A randomized, open label, parallel group, active controlled pre and post test clinical study was conducted comprising of 30 subjects. They were randomly allocated into 2 groups, subjects of Group A received Vyaghriharitaki Avaleha 5g BD and subjects of Group B received Vidangadi Churna 5g BD for 30 days. AEC and Signs & symptoms of Vataja Kasa were assessed before (0th day) and after treatment (30th day), after follow up (45th day). The data obtained were recorded, tabulated and statistically analyzed using Unpaired t test, Paired t Test, Mann Whitney U Test, Wilcoxon Signed rank test. Results: Analysis of the data within groups showed statistically highly significant (p<0.01) results and between the groups analysis showed statistically non-significant (p>0.05) results in reducing AEC and signs & symptoms of Vataja Kasa suggesting almost similar action of both drugs. Conclusion: It can be inferred that Vyaghriharitaki Avaleha is as efficient as Vidangadi Churna in the management of Vataja Kasa.

Analysis of COVID-19 patients hospitalized in general wards and intensive care units: Insights from the RIMAC cardiopulmonary imaging registry across Latin American centers.

This study aimed to compare various aspects among coronavirus disease 2019 (COVID-19) patients admitted to general wards versus intensive care units (ICUs) in Latin American (LATAM), including demographics, comorbidities, imaging and laboratory findings, complications, treatments, and predictors of mortality. Data from the LATAM cardiopulmonary imaging registry of hospitalized COVID-19 patients (RIMAC) were analyzed. RIMAC is a prospective observational study conducted from March to December 2020 across 12 tertiary centers in nine LATAM countries. Out of 1,435 patients, 49.34% were admitted to general wards and 50.66% to ICUs. Significant differences were observed between the two groups. ICU patients had a higher incidence of comorbidities, elevated biomarker levels, and complications such as kidney and heart failure, and required more intensive treatments. They also showed more severe imaging findings and had longer hospital stays with higher mortality rates compared to ward patients. The study highlighted significant disparities between COVID-19 patients admitted to general wards and ICUs in LATAM. These disparities encompassed clinical severity, resource utilization, and mortality rates. Older age, obesity, extensive lung infiltrates, and kidney failure emerged as predictors of mortality. These findings underscore the need for tailored management strategies based on the severity of illness among COVID-19 patients in LATAM.

Cxcl10 is protective during mouse-adapted SARS-CoV-2 infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of the coronavirus disease 2019 (COVID-19) pandemic, remains endemic worldwide. Circulating levels of the chemokine CXCL10 are strongly positively associated with poor outcome; however, its precise role in SARS-CoV-2 pathogenesis and its suitability as a therapeutic target have remained undefined. Here, we challenged mice genetically deficient in Cxcl10 with a mouse-adapted strain of SARS-CoV-2. Infected male, but not female, Cxcl10-/- mice displayed increased mortality compared to wild type controls. Histopathological damage, inflammatory gene induction and virus load in the lungs of male mice were not broadly influenced by Cxcl10 deficiency. However, accumulation of B and T lymphocytes in the lung parenchyma of infected mice was reduced in the absence of Cxcl10. Thus, during acute SARS-CoV-2 infection, Cxcl10 regulates lymphocyte infiltration in lung and confers protection against mortality. Our preclinical model results do not support targeting CXCL10 therapeutically in severe COVID-19.

Open-lung ventilation versus no ventilation during cardiopulmonary bypass in an innovative animal model of heart transplantation

Open-lung ventilation during cardiopulmonary bypass (CPB) in patients undergoing heart transplantation (HTx) is a potential strategy to mitigate postoperative acute respiratory distress syndrome (ARDS). We utilized an ovine HTx model to investigate whether open-lung ventilation during CPB reduces postoperative lung damage and complications. Eighteen sheep from an ovine HTx model were included, with ventilatory interventions randomly assigned during CPB: the OPENVENT group received low tidal volume (VT) of 3 mL/kg and positive end-expiratory pressure (PEEP) of 8 cm H20, while no ventilation was provided in the NOVENT group as per standard of care. The recipient sheep were monitored for 6 h post-surgery. The primary outcome was histological lung damage, scored at the end of the study. Secondary outcomes included pulmonary shunt, driving pressure, hemodynamics and inflammatory lung infiltration. All animals completed the study. The OPENVENT group showed significantly lower histological lung damage versus the NOVENT group (0.22 vs 0.27, p = 0.042) and lower pulmonary shunt (19.2 vs 32.1%, p = 0.001). In addition, the OPENVENT group exhibited a reduced driving pressure (9.6 cm H2O vs. 12.8 cm H2O, p = 0.039), lower neutrophil (5.25% vs 7.97%, p ≤ 0.001) and macrophage infiltrations (11.1% vs 19.6%, p < 0.001). No significant differences were observed in hemodynamic parameters. In an ovine model of HTx, open-lung ventilation during CPB significantly reduced lung histological injury and inflammatory infiltration. This highlights the value of an open-lung approach during CPB and emphasizes the need for further clinical evidence to decrease risks of lung injury in HTx patients.

Acute exacerbation of progressive pulmonary fibrosis: incidence and outcomes.

Few data are available on acute exacerbation (AE) in patients with progressive pulmonary fibrosis (PPF) besides idiopathic pulmonary fibrosis (IPF). This study aimed to investigate the AE incidence and outcomes among patients with PPF. Clinical data of patients with PPF (n = 133) were retrospectively collected at a single center. PPF was defined based on the criteria used in the INBUILD trial. AE was defined as a worsening of dyspnea typically within 30 days with new bilateral lung infiltration and no evidence of cardiac failure or fluid overload. Among patients with PPF, the mean age was 60.6 years old, 57.1% were females, and the most common etiology was connective tissue disease-related ILDs (63%). During the follow-up (median: 38.0 months) after PPF diagnosis, 42 patients (31.6%) experienced AE. The 1-, 3-, and 5-year AE incidences were 12.5%, 30.3%, and 38.0%, respectively. Older age, rheumatoid arthritis associated ILD, fibrotic hypersensitivity pneumonitis, and lower lung diffusing capacity for carbon monoxide were AE risk factors. Patients with AE demonstrated worse survival (median survival: 30 months vs. not reached; p < 0.001) after PPF diagnosis than those without. AE was independently associated with mortality in patients with PPF (hazard ratio [HR], 2.194; 95% confidence interval [CI], 1.285-3.747; p = 0.004) in the multivariable Cox analysis, along with older age, lower lung diffusing capacity for carbon monoxide, and the usual interstitial pneumonia-like pattern on high-resolution computed tomography. Our results suggest AE is not uncommon and significantly impacts on survival in patients with PPF.

Clinical outcome of severe and critical covid patient receiving NIV or invasive ventilation

BackgroundOxygen support therapy plays a pivotal role in managing severe COVID-19 pneumonias causing respiratory failure. Non-invasive ventilation (NIV) strategies are commonly suggested methods to improve oxygenation in such patients.ObjectiveWe aimed to determine clinical outcomes in hypoxemic COVID-19 patients receiving non-invasive vs. invasive ventilation.Material and methodsThis cross-sectional study was conducted on 40 patients who tested positive by RT-PCR for SARS-CoV-2 RNA and required either invasive or NIV and admitted to the ICU of the 15th of May hospital for 3 months from June 2022 to August 2022. Patients were classified as: Severe: SpO2 < 90%, Pao2\\FiO2 < 300, RR > 30, or lung infiltrate > 50%. Critical: the above criteria plus respiratory failure, septic shock, and\\or multiorgan dysfunction.ResultsThere was a significant difference between the two groups regarding shifting to another mode and ferritin levels. In the NIV group, seven patients were successfully discharged and only two patients were discharged in the invasive group. There was a significant difference between critical and severe regarding length of stay (ICU and Hospital). The Kaplan-Meier survival curve for dead cases showed that the mortality occurrence was significant in invasive ventilation than NIV group with mean duration free from death in NIV group 18.8 compared to 14.8 in the invasive ventilation group.ConclusionsThe NIV use in subjects with critical-to-severe COVID-19 was successful in most of the subjects and can be a safe treatment option. Invasive mechanical ventilation is associated with adverse outcomes possibly due to ventilator-associated lung injury.

Abstract 428: The Unusual Suspect ‐ Hypereosinophilia as the Cause for Acute Stroke

Background Eosinophilic granulomatosis with polyangiitis (EGPA) causes inflammation of small blood vessels. EGPA is rare, with an annual incidence of 1 per million, with a mean age of onset of 40‐60 years. EGPA is divided into 2 phenotypes, ANCA‐positive vasculitis type and ANCA‐negative eosinophilia type. There is an overlap between other hypereosinophilic syndromes and EGPA. There are no diagnostic criteria for EGPA, however clinical features of asthma, chronic rhinosinusitis with polyps, eosinophilia, neuropathy, lung infiltrates, and eosinophilic cardiomyopathy or gastroenteritis are supportive. Central nervous system involvement manifests as cerebral infarcts and subarachnoid hemorrhages. Case: Here we present a 53‐year‐old Caucasian female with no past medical history who presented with chest pain and shortness of breath. She reported dyspnea on exertion for 8 months prior, and more recently paroxysmal nocturnal dyspnea and orthopnea, with minimal relief from inhalers. She was noted to have pansinusitis and was started on amoxicillin‐clavulanic acid without improvement. She noted acute right upper extremity weakness. Initial workup showed elevated troponin and a white blood cell (WBC) count of 28.4 with 11.64 eosinophils. CT chest showed bilateral bronchial wall thickening with bilateral nodular consolidative opacities in the right upper lobe and left lower lobe. She was started on a heparin drip. Coronary angiography was negative, and the initial echocardiogram revealed mild circumferential pericardial effusion without tamponade. CT head showed an 11 mm right cerebellar hemorrhage. Heparin was stopped. MRI brain revealed multiple scattered areas of restricted diffusion in bilateral cerebral hemispheres and a right cerebellar hemisphere. CTA head and neck showed normal vessels, and after transfer to our facility, a repeat MRI brain revealed scattered new infarcts in the left parietal and occipital regions. A repeat echocardiogram showed a small loculated pericardial effusion anterior to the right ventricle but no intracardiac shunt. The patient was exposed to wildfire smoke before symptom onset, raising suspicion of fungal infection. The patient underwent fungal evaluation in both serum and sinus aspirate, including beta‐D‐glucan in the serum, which was negative, and a bronchoscopy, which revealed white plaques and nodules with negative fungal and tuberculosis studies. Lumbar puncture revealed an elevated opening pressure of 30 mmHg but otherwise unremarkable infectious studies. Antibiotic therapy included vancomycin, cefepime, and amphotericin, but with consistently elevated WBCs of more than 24 with eosinophilic predominance. Endomyocardial biopsy showed numerous eosinophils. Subsequent endobronchial biopsy showed eosinophilic infiltrates and features suspicious for vasculitis. ANCA and bone marrow biopsy were negative. The primary diagnosis was considered hypereosinophilic syndrome. She was started on pulse dose steroids, and WBC count fell from 24.1 to 11.8 with a decrease in eosinophils from 13.05 to 0.01. Outpatient rheumatology was planned to initiate cyclophosphamide or rituximab. Dual antiplatelet therapy was initiated before discharge. Conclusion Central nervous system sequelae of EGPA are rare, but this diagnosis should be considered in patients with symptoms of sinusitis, elevated eosinophils, and acute stroke, especially without other risk factors. Since ANCA is only positive in about 30‐40% of patients, an early biopsy is needed for confirmation and early treatment with steroids.

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.

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.