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Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare and critical malignancy‐related disease characterized by acute progressive pulmonary hypertension (PH). In most cases of PTTM, the cancer can be diagnosed in advance. Identification of the primary cancer is valuable for PTTM diagnosis. Here, we present the case of a patient with PTTM due to early gastric carcinoma in whom the diagnosis of malignant cancer was not revealed until macroscopic autopsy findings. This case highlights the importance of recognizing causative occult early gastric cancer leading to PTTM in cases of acute progressive PH. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a viral pneumonia characterized by acute interstitial pneumonia and diffuse alveolar damage in humans. Non-human primates (NHPs) are widely used as preclinical animal models for vaccine development against SARS-CoV-2. However, the pathological changes in NHPs have been described only in selected facets and inconsistent nomenclature is used, making it difficult to interpret and compare the outcomes between studies. Here, we present a standardized methodology for histopathological evaluation of experimental infection outcomes in rhesus (Macaca mulatta) and cynomolgus (Macaca fascicularis) macaques. Evaluation criteria for vascular and epithelial changes in the early (3 days post infection [dpi]) and late (21 dpi) phases of the infection were developed, and a four-grade classification encompassing all the histopathological lung lesions was established. The grades of histopathological lung lesions were higher at 3 dpi compared with 21 dpi in both species of macaques, and there were no statistically significant differences in the grades between the two species at 3 dpi and 21 dpi. This study contextualized the pathological SARS-CoV-2 presentation and standardized the terminology and grading scale for lesion severity to facilitate histopathological examination in the macaque model. By referring to the standardized histopathological criteria and grades proposed here, comparable results with high reproducibility can be obtained in future studies of pathogenicity. [ABSTRACT FROM AUTHOR]

Minimally invasive autopsies (MIAs) allow the collection of tissue samples for diagnostic and research purposes in special situations, e.g., when there is a high risk of infection which is the case in the context of COVID-19 or restrictions due to legal or personal reasons. We performed MIA to analyze lung tissue from 92 COVID-19 patients (mean age 78 years; range 48–98; 35 women, 57 men), representing 44% of all patients who died from the disease between October 2020 and April 2021. An intercostal approach was used with removal of a 5-cm rib section followed by manual collection of four lung tissue samples (5–8 cm in size). Diffuse alveolar damage (DAD) was found in 89 (97%) patients at various stages. Exudative DAD (eDAD) predominated in 18 (20%) patients, proliferative DAD (pDAD) in 43 (47%) patients, and mixed DAD (mDAD) in 31 (34%) patients. There were no significant differences in the predominant DAD pattern between tissue samples from the same patient. Additional purulent components were present in 46 (50%) cases. Fungi were detected in 11 (12%) patients. The pDAD pattern was associated with longer hospital stay including intensive care unit (p=0.026 and p<0.001) and younger age (p=0.019). Positive bronchoalveolar lavage and blood cultures were observed more frequently in pDAD patterns (p<0.001; p=0.018). In contrast, there was no significant association between intravital positive microbiological results and superimposed bronchopneumonia or fungal infection at autopsy. Having demonstrated the characteristic lung changes in a large longitudinal autopsy series, we conclude that the presented MIA approach can be considered a reliable and safe method for performing post mortem lung diagnostics in COVID-19 and other high-risk situations. The lack of correlation between histological changes indicative of bacterial or fungal superinfection and microbiology could have clinical implications for disease and treatment surveillance. [ABSTRACT FROM AUTHOR]

Abstract Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare and critical malignancy‐related disease characterized by acute progressive pulmonary hypertension (PH). In most cases of PTTM, the cancer can be diagnosed in advance. Identification of the primary cancer is valuable for PTTM diagnosis. Here, we present the case of a patient with PTTM due to early gastric carcinoma in whom the diagnosis of malignant cancer was not revealed until macroscopic autopsy findings. This case highlights the importance of recognizing causative occult early gastric cancer leading to PTTM in cases of acute progressive PH.

Objectives Mesothelioma is a lethal disease that arises from the serosal lining of organ cavities. Several recurrent alterations have been observed in pleural and peritoneal -mesotheliomas, including in BAP1, NF2, and CDKN2A. Although specific histopathologic parameters have been correlated with prognosis, it is not as well known whether genetic alterations correlate with histologic findings. Methods We reviewed 131 mesotheliomas that had undergone next-generation sequencing (NGS) at our institutions after pathologic diagnosis. There were 109 epithelioid mesotheliomas, 18 biphasic mesotheliomas, and 4 sarcomatoid mesotheliomas. All our biphasic and sarcomatoid cases arose in the pleura. Of the epithelioid mesotheliomas, 73 were from the pleura and 36 were from the peritoneum. On average, patients were 66 years of age (range, 26-90 years) and predominantly male (92 men, 39 women). Results The most common alterations identified were in BAP1, CDKN2A, NF2, and TP53. Twelve mesotheliomas did not show a pathogenic alteration on NGS. For epithelioid mesotheliomas in the pleura, the presence of an alteration in BAP1 correlated with low nuclear grade (P =.04), but no correlation was found in the peritoneum (P =.62). Similarly, there was no correlation between the amount of solid architecture in epithelioid mesotheliomas and any alterations in the pleura (P =.55) or peritoneum (P =.13). For biphasic mesotheliomas, cases with either no alteration detected or with an alteration in BAP1 were more likely to be epithelioid predominant (>50% of the tumor, P =.0001), and biphasic mesotheliomas with other alterations detected and no alteration in BAP1 were more likely to be sarcomatoid predominant (>50% of the tumor, P =.0001). Conclusions This study demonstrates a significant association between morphologic features associated with a better prognosis and an alteration in BAP1. [ABSTRACT FROM AUTHOR]

We report the case of a 59‐year‐old female patient, presenting with pustular rash on both hands and pain in the lumbosacral part and left lower limb. A magnetic resonance imaging examination of the left leg was undertaken and the result showed that a malignant lesion with bone destruction of the left femoral shaft could not be excluded. Subsequently, bone tumor was excluded by pathological examination. Lung computed tomography scan showed patchy consolidation and cord shadow in the middle left lung. Subsequently, lung cancer was excluded by pathological examination, and the histopathological changes of lung were consistent with those of organized pneumonia. Blood tests revealed elevated C‐reactive protein and erythrocyte sedimentation rate. Antinuclear antibody, rheumatoid factor, and human leukocyte antigen‐B27 were unremarkable. Whole body bone scintigraphy via technetium 99m‐methyl diphosphonate showed increased radionuclide uptake in the left middle femur. Based on her clinical manifestations, imaging results and bone scintigraphy, the patient was diagnosed as having synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome. Loxoprofen and Tripterygium wilfordii Hook F led to impressive clinical and radiologic improvement. [ABSTRACT FROM AUTHOR]

Background. In recent decades, along with the growth of allergic diseases, there has been a progressive increase in the number of people with overweight of varying severity, as evidenced by numerous epidemiological studies. Therefore, both allergies and obesity are among the global problems of modern healthcare due to their high prevalence and medical and social significance. The purpose of the study was analysis of the etiological factors of chronic urticaria (CU) in obese patients with pulmonary pathology, optimization of diagnosis and treatment of CU for further planning of preventive measures. Materials and methods. We examined 250 patients who applied for medical care to the regional clinical hospital in Chernivtsi and had CU associated with pulmonary pathology and obesity. Based on the analysis of the obtained data, a group of 140 patients was formed for further clinical and anamnestic examination: analysis of the anamnesis, determination of the severity of urticaria, assessment of quality of life, control of urticaria symptoms, general clinical laboratory studies, tests for verification of urticaria. Allergy testing was carried out when the patient’s anamnestic data indicated its expediency. The survey was carried out for one month and included a diagnostic period and 3 consultations every 7–10 days. Results. Among the causes of CU in patients with pulmonary disease, drug intolerance and parasitic infection dominate. Polyetiology is observed in 60 % of cases. Differences in CU in obese patients are the long-term persistence of urticaria or other elements of the rash, the lack of effectiveness of therapy with the second- and third-generation antihistamines and glucocorticosteroids. Conclusions. The results obtained indicate a positive effect of the quinuclidine derivative quifenadine for the treatment of CU in patients with pulmonary pathology and obesity. Complete and significant effects were obtained in 91.43 % of patients. The worst results (8.57 %) were demonstrated by patients with the etiological significance of chemical factors (including occupational ones), which is associated with more problematic compliance with the elimination regimen in this category of patients.

Background: Non-thrombotic pulmonary embolism, an uncommon entity, is defined as the embolization of tissues, microorganisms, air, or foreign material. One subset in this non-thrombotic category is septic pulmonary embolism (SPE) that refers to embolism of microorganisms with or without a thrombotic mantle into the pulmonary vasculature. This condition is often recognized on the basis of imaging with a clinical correlation. Unfortunately, data regarding the pathological features are meager. This has prompted to review such cases at autopsy. Aims: To study the pathological features of SPE at autopsy. Materials and Methods: Ten-year (2012 to 2021) autopsy records of the hospital were retrospectively reviewed. The diagnosis was based on the identification of acute necrotizing pulmonary arteritis with peri-bronchoarterial consolidation. These cases were analyzed with reference to the demographics, clinical characteristics, and pulmonary/extrapulmonary findings at autopsy. Statistical Analysis: Nil. Results: According to the inclusion criterion, 19 cases demonstrated the presence of SPE. There were 11 men and 8 women with a mean age of 32.1 years. The major source of infection included infection arising from skin and musculo-skeletal system (11 patients, 59.7%). The common clinical presentation included fever, dyspnea, chest pain, hemoptysis, and altered sensorium. The cause of death was mainly due to septicemia and/or confluent lung consolidations. A large number of bacterial colonies were seen in all; Candida species were also identified in two cases. Other lung findings included diffuse alveolar damage, fresh arterial thrombosis, infarction, arterial pseudo-aneurysms, abscess formation, and pyogenic pleuritis. Conclusion: Presence of an extrapulmonary infection with persistent fever, bacteremia, and pulmonary complaints should raise suspicion for this entity, particularly in resource-poor settings, to prevent grave pulmonary complications.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel entry in the betacoronaviridae group of coronaviruses. This is the second member of this group, and the third of the family overall to emerge in the last 20 years, which has caused significant health concerns due to the clinical severity and spread of the disease it causes—coronavirus disease identified in 2019 (COVID-19). While initially emerging as a respiratory disease, and while most cases experience symptoms predominantly from this system, SARS-CoV-2 has emerged as a multisystem pathogen. From a pathomorphological point of view, the severity of changes in the respiratory system can be summed up as diffuse alveolar damage—desquamation of the alveolar epithelium with exudative and proliferative changes—pulmonary hyaline membranes, Clara cell hyperplasia, squamous cell metaplasia, and fibrosis. The second most prominent way the disease affects the lung is through endotheliitis—damage to the endothelial cells of the pulmonary vasculature, predominantly affecting the medium and large caliber blood vessels that cause the well-established clinical phenomenon of thrombosis/thromboembolism of the pulmonary vasculature. As the spread of the disease continues with the emergence of new variants and the number of cases continues to grow, including a large percentage of recurrent cases, it is essential to remember that the viral effects are not only acute but, due to the proliferative phenomena, can produce chronic sequelae. Therefore, in the background of dwindling publication interest, it is critical to focus on the histopathological aspects of the pulmonary disease, with the goal of better understanding the effects of the virus on the organism and identifying probable future complications after infection.

Background. In recent decades, along with the growth of allergic diseases, there has been a progressive increase in the number of people with overweight of varying severity, as evidenced by numerous epidemiological studies. Therefore, both allergies and obesity are among the global problems of modern healthcare due to their high prevalence and medical and social significance. The purpose of the study was analysis of the etiological factors of chronic urticaria (CU) in obese patients with pulmonary pathology, optimization of diagnosis and treatment of CU for further planning of preventive measures. Materials and methods. We examined 250 patients who applied for medical care to the regional clinical hospital in Chernivtsi and had CU associated with pulmonary pathology and obesity. Based on the analysis of the obtained data, a group of 140 patients was formed for further clinical and anamnestic examination: analysis of the anamnesis, determination of the severity of urticaria, assessment of quality of life, control of urticaria symptoms, general clinical laboratory studies, tests for verification of urticaria. Allergy testing was carried out when the patient’s anamnestic data indicated its expediency. The survey was carried out for one month and included a diagnostic period and 3 consultations every 7–10 days. Results. Among the causes of CU in patients with pulmonary disease, drug intolerance and parasitic infection dominate. Polyetiology is observed in 60 % of cases. Differences in CU in obese patients are the long-term persistence of urticaria or other elements of the rash, the lack of effectiveness of therapy with the second- and third-generation antihistamines and glucocorticosteroids. Conclusions. The results obtained indicate a positive effect of the quinuclidine derivative quifenadine for the treatment of CU in patients with pulmonary pathology and obesity. Complete and significant effects were obtained in 91.43 % of patients. The worst results (8.57 %) were demonstrated by patients with the etiological significance of chemical factors (including occupational ones), which is associated with more problematic compliance with the elimination regimen in this category of patients. [ABSTRACT FROM AUTHOR]

Definition: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel entry in the betacoronaviridae group of coronaviruses. This is the second member of this group, and the third of the family overall to emerge in the last 20 years, which has caused significant health concerns due to the clinical severity and spread of the disease it causes—coronavirus disease identified in 2019 (COVID-19). While initially emerging as a respiratory disease, and while most cases experience symptoms predominantly from this system, SARS-CoV-2 has emerged as a multisystem pathogen. From a pathomorphological point of view, the severity of changes in the respiratory system can be summed up as diffuse alveolar damage—desquamation of the alveolar epithelium with exudative and proliferative changes—pulmonary hyaline membranes, Clara cell hyperplasia, squamous cell metaplasia, and fibrosis. The second most prominent way the disease affects the lung is through endotheliitis—damage to the endothelial cells of the pulmonary vasculature, predominantly affecting the medium and large caliber blood vessels that cause the well-established clinical phenomenon of thrombosis/thromboembolism of the pulmonary vasculature. As the spread of the disease continues with the emergence of new variants and the number of cases continues to grow, including a large percentage of recurrent cases, it is essential to remember that the viral effects are not only acute but, due to the proliferative phenomena, can produce chronic sequelae. Therefore, in the background of dwindling publication interest, it is critical to focus on the histopathological aspects of the pulmonary disease, with the goal of better understanding the effects of the virus on the organism and identifying probable future complications after infection. [ABSTRACT FROM AUTHOR]

Epithelioid hemangioendothelioma (EHE) is a rare neoplasm of a vascular origin which can arise in different locations such as the lungs, liver, soft tissue, and rarely, in the bones. In the lungs, pulmonary hemangioendothelioma (PEH) shows a variable clinical behavior, displaying a range from either an asymptomatic course to a highly aggressive progression with metastases. Based on radiological features, PEH differential diagnosis mainly includes primary or metastatic lymphangitic carcinomatosis, granulomatous infections, and diffuse interstitial lung diseases where ground glass pattern predominates. In this case, a transbronchial biopsy and subsequent histological and immunohistochemical analysis allowed for the attribution of the scenario to a pulmonary epithelioid hemangioendothelioma. Clinicians should always consider bronchoscopy as a useful and effective tool to better investigate indeterminate and questionable clinical pictures, sparing patients the morbidity and mortality associated with more invasive techniques such as surgical or thoracoscopic biopsy. [ABSTRACT FROM AUTHOR]

Simple Summary: The use of cross-sectional imaging techniques to examine the cause of death and health status of deceased animals is increasing in both veterinary and wildlife conservation programs, including species of whales and dolphins. Lung disease is common in harbor porpoises (Phocoena phocoena), a small whale species that regularly washes up on the coast in North Sea-bordering countries. This study aimed to describe lung changes visible in computed tomographic (CT) images of recently deceased harbor porpoises before pathological dissection was performed, including comparison of these two examination methods. Despite frequently visible signs of body decomposition, several lung abnormalities (collapsed lung, fluid in the airways, lung mineralization) were more often seen on the CT images. In general, lung changes could be described in more detail compared to gross dissection. CT images of lungs of recently deceased harbor porpoises can therefore be used to guide gross dissection, leading to more specific findings and potentially a more complete understanding of the circumstances leading to the death of the porpoise, assessment of the population, and ultimately, ecosystem health. The application of whole-body post-mortem computed tomography (PMCT) in veterinary and wildlife post-mortem research programs is advancing. A high incidence of pulmonary pathology is reported in the harbor porpoise (Phocoena phocoena). In this study, the value of PMCT focused on pulmonary assessment is evaluated. The objectives of this study were to describe pulmonary changes as well as autolytic features detected by PMCT examination and to compare those findings with conventional necropsy. Retrospective evaluation of whole-body PMCT images of 46 relatively fresh harbor porpoises and corresponding conventional necropsy reports was carried out, with a special focus on the respiratory tract. Common pulmonary PMCT findings included: moderate (24/46) to severe (19/46) increased pulmonary soft tissue attenuation, severe parasite burden (17/46), bronchial wall thickening (30/46), and mild autolysis (26/46). Compared to conventional necropsy, PMCT more frequently identified pneumothorax (5/46 vs. none), tracheal content (26/46 vs. 7/46), and macroscopic pulmonary mineralization (23/46 vs. 11/46), and provided more information of the distribution of pulmonary changes. These results indicate that PMCT adds information on pulmonary assessment and is a promising complementary technique for necropsy, despite the frequent presence of mild autolytic features. [ABSTRACT FROM AUTHOR]

Pulmonary tumor thrombotic microangiopathy (PTTM) is a disease process wherein tumor cells are thought to embolize to the pulmonary circulation causing pulmonary hypertension (PH) and death from right heart failure. Presented herein are clinical, laboratory, radiographic, and histologic features across seven cases of PTTM. Highlighted in this publication are also involvement of pulmonary venules and clinical features distinguishing PTTM from clinical mimics. We conducted a retrospective chart review of seven cases of PTTM from hospitals in the greater Los Angeles metropolitan area. Patients in this series exhibited: symptoms of cough and progressive dyspnea; PH and/or heart failure on physical exam; laboratory abnormalities of anemia, thrombocytopenia, elevated LDH, and elevated D-dimer; chest computed tomography (CT) showing diffuse septal thickening, mediastinal and hilar lymphadenopathy and nodules; elevated pulmonary artery pressures on transthoracic echocardiogram and/or right heart catheterization; and presence of malignancy. Tumor emboli and fibrocellular intimal proliferation were seen in pulmonary arterioles, while two patients had pulmonary venopathy. PTTM is a devastating disease occurring in patients with metastatic carcinoma. An early diagnosis is challenging. Understanding the clinical presentation of PTTM and distinguishing PTTM from clinical mimics may help achieve an early diagnosis and allow time for initiation of treatment.

Background Hypersensitivity pneumonitis (HP) infrequently presents in childhood. Asthma or a pneumonia-like clinical presentation may lead to diagnostic delay, especially in children. Case Report: We present two cases of HP, a 6-year-old (Case 1) male and a 5-year-old (Case 2) female. Both cases had a negative infectious work-up and patchy ground glass lung opacities on chest computed tomography. Lung biopsies demonstrated lymphocytic bronchiolitis with granulomatous interstitial and peribronchial inflammation. Serology demonstrated elevated immunoglobulin precipitins toward Thermoactinomyces and Aspergillus species in Case 1 and Aspergillus fumigatus in Case 2. Both patients received steroid therapy and had symptom resolution. Conclusions: A diagnosis of HP should be considered in pediatric lung biopsies with granulomatous interstitial and peribronchial inflammation, if infectious etiologies are excluded. Integration of clinical, radiological, and laboratory findings can facilitate a timely diagnosis. [ABSTRACT FROM AUTHOR]

Abstract Background Diabetes mellitus type 2 (DM) may impede immune responses in tuberculosis (TB) and thus contribute to enhanced disease severity. In this study, we aimed to evaluate DM-mediated alterations in clinical, radiological and immunological outcomes in TB disease. Methods Newly diagnosed pulmonary TB patients with or without DM (TB n = 40; TB-DM n = 40) were recruited in Dhaka, Bangladesh. Clinical symptoms, sputum smear and culture conversion as well as chest radiography were assessed. Peripheral blood and sputum samples were collected at the time of diagnosis (baseline) and after 1, 2 and 6 months of standard anti-TB treatment. Blood samples were also obtained from healthy controls (n = 20). mRNA expression of inflammatory markers in blood and sputum samples were quantified using real-time PCR. Results The majority of TB-DM patients had poor glycemic control (HbA1c > 8%) and displayed elevated pulmonary pathology (P = 0.039) particularly in the middle (P

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ABSTRACTEnterovirus 71 (EV71) is a major pathogen that causes hand, foot and mouth disease (HFMD), which is a life threatening disease in certain children. The pathogenesis of EV71-caused HFMD is poorly defined due to the lack of simple and robust animal models with severe phenotypes that recapitulate symptoms observed in humans. Here, we generated the infectious clone of a clinical isolate from a severe HFMD patient. Virus rescued from the cDNA clone was infectious in cell lines. When administrated intraperitoneally to neonatal ICR, BALB/c and C57 immune competent mice at a dosage of1.4 × 104 pfu per mouse, the virus caused weight loss, paralysis and death in the infected mice after 4–5 days of infection. In the infected mice, detectable viral replication was detected in various tissues such as heart, liver, brain, lung, kidney, small intestine, leg skeletal muscle and medulla oblongata. The histology of the infected mice included massive myolysis, glomerular atrophy, villous blunting in small intestine, widened alveolar septum, diminished alveolar spaces and lymphocytes infiltration into the lung. By using the UV-inactivated virus as a control, we elucidated that the virus first amplified in the leg skeletal muscle tissue and the muscle tissue served as a primary viral replication site. In summary, we generated a stable EV71 infectious clone that is capable of infecting neonatal immune competent mice without adaptive mutations and provide a simple, valuable animal model for the studies of EV71pathogenesis and therapy.

The World Health Organization (WHO) highlights a greater susceptibility of males to tuberculosis (TB), a vulnerability attributed to sex-specific variations in body fat and dietary factors. Our study delves into the unexplored terrain of how alterations in body fat influence Mycobacterium tuberculosis ( Mtb ) burden, lung pathology, immune responses, and gene expression, with a focus on sex-specific dynamics. Utilizing a low-dose Mtb -HN878 clinical strain infection model, we employ transgenic FAT-ATTAC mice with modulable body fat to explore the impact of fat loss (via fat ablation) and fat gain (via a medium-fat diet, MFD). Firstly, our investigation unveils that Mtb infection triggers severe pulmonary pathology in males, marked by shifts in metabolic signaling involving heightened lipid hydrolysis and proinflammatory signaling driven by IL-6 and localized pro-inflammatory CD8 + cells. This stands in stark contrast to females on a control regular diet (RD). Secondly, our findings indicate that both fat loss and fat gain in males lead to significantly elevated (1.6-fold ( p ≤ 0.01) and 1.7-fold ( p ≤ 0.001), respectively) Mtb burden in the lungs compared to females during Mtb infection (where fat loss and gain did not alter Mtb load in the lungs). This upsurge is associated with impaired lung lipid metabolism and intensified mitochondrial oxidative phosphorylation-regulated activity in lung CD8 + cells during Mtb infection. Additionally, our research brings to light that females exhibit a more robust systemic IFNγ ( p ≤ 0.001) response than males during Mtb infection. This heightened response may either prevent active disease or contribute to latency in females during Mtb infection. In summary, our comprehensive analysis of the interplay between body fat changes and sex bias in Mtb infection reveals that alterations in body fat critically impact pulmonary pathology in males. Specifically, these changes significantly reduce the levels of pulmonary CD8 + T-cells and increase the Mtb burden in the lungs compared to females. The reduction in CD8 + cells in males is linked to an increase in mitochondrial oxidative phosphorylation and a decrease in TNFα, which are essential for CD8 + cell activation.

Epithelioid hemangioendothelioma (EHE) is a rare neoplasm of a vascular origin which can arise in different locations such as the lungs, liver, soft tissue, and rarely, in the bones. In the lungs, pulmonary hemangioendothelioma (PEH) shows a variable clinical behavior, displaying a range from either an asymptomatic course to a highly aggressive progression with metastases. Based on radiological features, PEH differential diagnosis mainly includes primary or metastatic lymphangitic carcinomatosis, granulomatous infections, and diffuse interstitial lung diseases where ground glass pattern predominates. In this case, a transbronchial biopsy and subsequent histological and immunohistochemical analysis allowed for the attribution of the scenario to a pulmonary epithelioid hemangioendothelioma. Clinicians should always consider bronchoscopy as a useful and effective tool to better investigate indeterminate and questionable clinical pictures, sparing patients the morbidity and mortality associated with more invasive techniques such as surgical or thoracoscopic biopsy.

The application of whole-body post-mortem computed tomography (PMCT) in veterinary and wildlife post-mortem research programs is advancing. A high incidence of pulmonary pathology is reported in the harbor porpoise (Phocoena phocoena). In this study, the value of PMCT focused on pulmonary assessment is evaluated. The objectives of this study were to describe pulmonary changes as well as autolytic features detected by PMCT examination and to compare those findings with conventional necropsy. Retrospective evaluation of whole-body PMCT images of 46 relatively fresh harbor porpoises and corresponding conventional necropsy reports was carried out, with a special focus on the respiratory tract. Common pulmonary PMCT findings included: moderate (24/46) to severe (19/46) increased pulmonary soft tissue attenuation, severe parasite burden (17/46), bronchial wall thickening (30/46), and mild autolysis (26/46). Compared to conventional necropsy, PMCT more frequently identified pneumothorax (5/46 vs. none), tracheal content (26/46 vs. 7/46), and macroscopic pulmonary mineralization (23/46 vs. 11/46), and provided more information of the distribution of pulmonary changes. These results indicate that PMCT adds information on pulmonary assessment and is a promising complementary technique for necropsy, despite the frequent presence of mild autolytic features.

Background: Diabetes mellitus type 2 (DM) may impede immune responses in tuberculosis (TB) and thus contribute to enhanced disease severity. In this study, we aimed to evaluate DM-mediated alterations in clinical, radiological and immunological outcomes in TB disease.Methods: Newly diagnosed pulmonary TB patients with or without DM (TB n = 40; TB-DM n = 40) were recruited in Dhaka, Bangladesh. Clinical symptoms, sputum smear and culture conversion as well as chest radiography were assessed. Peripheral blood and sputum samples were collected at the time of diagnosis (baseline) and after 1, 2 and 6 months of standard anti-TB treatment. Blood samples were also obtained from healthy controls (n = 20). mRNA expression of inflammatory markers in blood and sputum samples were quantified using real-time PCR.Results: The majority of TB-DM patients had poor glycemic control (HbA1c > 8%) and displayed elevated pulmonary pathology (P = 0.039) particularly in the middle (P < 0.004) and lower lung zones (P < 0.02) throughout the treatment period. However, reduction of clinical symptoms and time to sputum smear and culture conversion did not differ between the groups. Transcripts levels of the pro-inflammatory cytokines IL-1β (P = 0.003 at month-1 and P = 0.045 at month-2) and TNF-α (P = 0.005 at month-1) and the anti-inflammatory cytokine IL-10 (P = 0.005 at month-2) were higher in peripheral blood after anti-TB treatment in TB-DM compared to TB patients. Conversely in sputum, TB-DM patients had reduced CD4 (P < 0.009 at month-1) and IL-10 (P = 0.005 at month-1 and P = 0.006 at month-2) transcripts, whereas CD8 was elevated (P = 0.016 at month-2). At 1- and 2-month post-treatment, sputum IL-10 transcripts were inversely correlated with fasting blood glucose and HbA1c levels in all patients.Conclusion: Insufficient up-regulation of IL-10 in the lung may fuel persistent local inflammation thereby promoting lung pathology in TB-DM patients with poorly controlled DM. [ABSTRACT FROM AUTHOR]

Objectives: Although diffuse alveolar damage, a subtype of acute lung injury (ALI), is the most common microscopic pattern in coronavirus disease 2019 (COVID-19), other pathologic patterns have been described. The aim of the study was to review autopsies from COVID-19 decedents to evaluate the spectrum of pathology and correlate the results with clinical, laboratory, and radiologic findings.Methods: A comprehensive and quantitative review from 40 postmortem examinations was performed. The microscopic patterns were categorized as follows: "major" when present in more than 50% of cases and "novel" if rarely or not previously described and unexpected clinically.Results: Three major pulmonary patterns were identified: ALI in 29 (73%) of 40, intravascular fibrin or platelet-rich aggregates (IFPAs) in 36 (90%) of 40, and vascular congestion and hemangiomatosis-like change (VCHL) in 20 (50%) of 40. The absence of ALI (non-ALI) was novel and seen in 11 (27%) of 40. Compared with ALI decedents, those with non-ALI had a shorter hospitalization course (P = .02), chest radiographs with no or minimal consolidation (P = .01), and no pathologically confirmed cause of death (9/11). All non-ALI had VCHL and IFPAs, and clinically most had cardiac arrest.Conclusions: Two distinct pulmonary phenotypic patterns-ALI and non-ALI-were noted. Non-ALI represents a rarely described phenotype. The cause of death in non-ALI is most likely COVID-19 related but requires additional corroboration. [ABSTRACT FROM AUTHOR]

Objectives: To report the methods and findings of two complete autopsies of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive individuals who died in Oklahoma (United States) in March 2020.Methods: Complete postmortem examinations were performed according to standard procedures in a negative-pressure autopsy suite/isolation room using personal protective equipment, including N95 masks, eye protection, and gowns. The diagnosis of coronavirus disease 2019 (COVID-19) was confirmed by real-time reverse transcriptase polymerase chain reaction testing on postmortem swabs.Results: A 77-year-old obese man with a history of hypertension, splenectomy, and 6 days of fever and chills died while being transported for medical care. He tested positive for SARS-CoV-2 on postmortem nasopharyngeal and lung parenchymal swabs. Autopsy revealed diffuse alveolar damage and chronic inflammation and edema in the bronchial mucosa. A 42-year-old obese man with a history of myotonic dystrophy developed abdominal pain followed by fever, shortness of breath, and cough. Postmortem nasopharyngeal swab was positive for SARS-CoV-2; lung parenchymal swabs were negative. Autopsy showed acute bronchopneumonia with evidence of aspiration. Neither autopsy revealed viral inclusions, mucus plugging in airways, eosinophils, or myocarditis.Conclusions: SARS-CoV-2 testing can be performed at autopsy. Autopsy findings such as diffuse alveolar damage and airway inflammation reflect true virus-related pathology; other findings represent superimposed or unrelated processes. [ABSTRACT FROM AUTHOR]

In this article author discusses about Idiopathic pulmonary fibrosis (IPF) that is a progressive form of fibrosing idiopathic interstitial pneumonitis characterized by radiographic and histopathologic usual interstitial pneumonia (UIP) pattern. Topics include examines that purposes of this perspective is to educate nonpathology physicians about the challenges faced by pathologists in the assessment of surgical lung biopsy (SLB) for interstitial lung disease (ILD).

Coronavirus disease 2019 (COVID-19) has shown the importance of postmortem investigation of deceased patients. For a correct interpretation of the pulmonary findings in this new era, it is, however, crucial to be familiar with pathologic pulmonary conditions observed in postmortem investigations in general. Adequate postmortem histopathological evaluation of the lungs may be affected by suboptimal gross work up, autolysis or poor fixation. Using a standardized preparation approach which consisted in instillation of 4% buffered formaldehyde through the large bronchi for proper fixation and preparing large frontal tissue sections of 1–2 cm thickness after at least 24 h fixation, we comprehensively analyzed postmortem pulmonary findings from consecutive adult autopsies of a two-year period before the occurrence of COVID-19 (2016–2017). In total, significant pathological findings were observed in 97/189 patients (51%), with 28 patients showing more than one pathologic condition. Acute pneumonia was diagnosed 33/128 times (26%), embolism 24 times (19%), primary pulmonary neoplasms 18 times (14%), organizing pneumonia and other fibrosing conditions 14 times (11%), pulmonary metastases 13 times (10%), diffuse alveolar damage 12 times (9%), severe emphysema 9 times (7%) and other pathologies, e.g., amyloidosis 5/128 times (4%). Pulmonary/cardiopulmonary disease was the cause of death in 60 patients (32%). Clinical and pathological diagnoses regarding lung findings correlated completely in 75 patients (40%). Autopsy led to confirmation of a clinically suspected pulmonary diagnosis in 57 patients (39%) and clarification of an unclear clinical lung finding in 16 patients (8%). Major discrepant findings regarding the lungs (N = 31; 16%) comprised cases with clinical suspicions that could not be confirmed or new findings not diagnosed intra vitam. A significant proportion of acute pneumonias (N = 8; 24% of all cases with this diagnosis; p = 0.011) was not diagnosed clinically. We confirmed the frequent occurrence of pulmonary pathologies in autopsies, including inflammatory and neoplastic lesions as the most frequent pathological findings. Acute pneumonia was an important cause for discrepancy between clinical and postmortem diagnostics

The curriculum vitae of Dr. Mark R. Wick contains 57 peer-reviewed publications, 3 editorials, 6 book chapters and a whole book dedicated to diseases of the lung and pleura. It is remarkable that such productivity should represent only a small portion of the overall output of Dr. Wick, which includes (at last count) 341 original peer-review publications, 119 invited review articles, 93 book chapters, 42 editorials, 3 society-related position papers, 18 books and 2 interactive video disks. Yet, his contributions to the literature in pulmonary and pleural pathology have been significant and influential and have established for him a national and international reputation as one of the leading experts in pulmonary pathology. Herein, it is my privilege to recount the various publications contributed by Dr. Wick to this topic, which span the gamut from transplant pathology to neoplastic diseases of the lung and pleura., Competing Interests: Declaration of competing interest There is no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Minimally invasive autopsies (MIAs) allow the collection of tissue samples for diagnostic and research purposes in special situations, e.g., when there is a high risk of infection which is the case in the context of COVID-19 or restrictions due to legal or personal reasons. We performed MIA to analyze lung tissue from 92 COVID-19 patients (mean age 78 years; range 48-98; 35 women, 57 men), representing 44% of all patients who died from the disease between October 2020 and April 2021. An intercostal approach was used with removal of a 5-cm rib section followed by manual collection of four lung tissue samples (5-8 cm in size). Diffuse alveolar damage (DAD) was found in 89 (97%) patients at various stages. Exudative DAD (eDAD) predominated in 18 (20%) patients, proliferative DAD (pDAD) in 43 (47%) patients, and mixed DAD (mDAD) in 31 (34%) patients. There were no significant differences in the predominant DAD pattern between tissue samples from the same patient. Additional purulent components were present in 46 (50%) cases. Fungi were detected in 11 (12%) patients. The pDAD pattern was associated with longer hospital stay including intensive care unit (p=0.026 and p<0.001) and younger age (p=0.019). Positive bronchoalveolar lavage and blood cultures were observed more frequently in pDAD patterns (p<0.001; p=0.018). In contrast, there was no significant association between intravital positive microbiological results and superimposed bronchopneumonia or fungal infection at autopsy. Having demonstrated the characteristic lung changes in a large longitudinal autopsy series, we conclude that the presented MIA approach can be considered a reliable and safe method for performing post mortem lung diagnostics in COVID-19 and other high-risk situations. The lack of correlation between histological changes indicative of bacterial or fungal superinfection and microbiology could have clinical implications for disease and treatment surveillance., (© 2023. The Author(s).)

Introduction: The mechanism of oxaliplatin (OXA) induced pulmonary toxicity is not fully understood. Aim of the study: The present study was designed to investigate the pulmonary toxicity of OXA that has been reported in previous studies. Study design: animal experiments. Material and methods: A total of 40 female Wistar rats were divided into 5 groups. In group 1, 5% glucose was injected intra-peritoneally; then the rats were sacrificed on day 14. OXA was administered in groups 2, 3, 4, and 5; then the animals were sacrificed on day 7 in group 2, day 14 in group 3, day 28 in group 4 and day 48 in group 5. The groups were further categorized as short-term administration and long-term administration groups. Furthermore, tissue glutathione peroxidase (GPX) activity was measured in all rats. Results: The mean GPX activities were 0.66 U/mg in the sham group, 0.74 U/mg in the short-term groups, and 0.74 U/mg in the long-term groups. We found that long-term OXA administration causes pulmonary toxicity resulting in increased intra-alveolar/interstitial macrophages and interstitial pneumonia. Similarly, we found reduced and permanent tissue GPX activity in rats that received OXA in higher doses and for a long term. Conclusions: Long-term OXA therapy causes toxic changes in the lung tissue. [ABSTRACT FROM AUTHOR]

Objectives: We compared minimally invasive tissue sampling (MITS) with conventional autopsy (CA) in detection of respiratory pathology/pathogens among Kenyan children younger than 5 years who were hospitalized with respiratory disease and died during hospitalization.Methods: Pulmonary MITS guided by anatomic landmarks was followed by CA. Lung tissues were triaged for histology and molecular testing using TaqMan Array Cards (TACs). MITS and CA results were compared for adequacy and concordance.Results: Adequate pulmonary tissue was obtained by MITS from 54 (84%) of 64 respiratory deaths. Comparing MITS to CA, full histologic diagnostic concordance was present in 23 (36%) cases and partial concordance in 19 (30%), an overall 66% concordance rate. Pathogen detection using TACs had full concordance in 27 (42%) and partial concordance in 24 (38%) cases investigated, an overall 80% concordance rate.Conclusions: MITS is a viable alternative to CA in respiratory deaths in resource-limited settings, especially if combined with ancillary tests to optimize diagnostic accuracy. [ABSTRACT FROM AUTHOR]

Background: Non-thrombotic pulmonary embolism, an uncommon entity, is defined as the embolization of tissues, microorganisms, air, or foreign material. One subset in this non-thrombotic category is septic pulmonary embolism (SPE) that refers to embolism of microorganisms with or without a thrombotic mantle into the pulmonary vasculature. This condition is often recognized on the basis of imaging with a clinical correlation. Unfortunately, data regarding the pathological features are meager. This has prompted to review such cases at autopsy., Aims: To study the pathological features of SPE at autopsy., Materials and Methods: Ten-year (2012 to 2021) autopsy records of the hospital were retrospectively reviewed. The diagnosis was based on the identification of acute necrotizing pulmonary arteritis with peri-bronchoarterial consolidation. These cases were analyzed with reference to the demographics, clinical characteristics, and pulmonary/extrapulmonary findings at autopsy., Statistical Analysis: Nil., Results: According to the inclusion criterion, 19 cases demonstrated the presence of SPE. There were 11 men and 8 women with a mean age of 32.1 years. The major source of infection included infection arising from skin and musculo-skeletal system (11 patients, 59.7%). The common clinical presentation included fever, dyspnea, chest pain, hemoptysis, and altered sensorium. The cause of death was mainly due to septicemia and/or confluent lung consolidations. A large number of bacterial colonies were seen in all; Candida species were also identified in two cases. Other lung findings included diffuse alveolar damage, fresh arterial thrombosis, infarction, arterial pseudo-aneurysms, abscess formation, and pyogenic pleuritis., Conclusion: Presence of an extrapulmonary infection with persistent fever, bacteremia, and pulmonary complaints should raise suspicion for this entity, particularly in resource-poor settings, to prevent grave pulmonary complications.

One of the most common systemic defects in patients with chronic obstructive pulmonary disease is skeletal and respiratory muscle dysfunction. Physical exercise in the therapy of such patients therefore plays an important role. The Institute of Pulmonology of the Russian FMBA has developed a system of special physical exercises to decrease dysfunction of respiratory and skeletal muscles and affect the hyperinflation of the lungs. The physical program includes strength exercises for upper and lower skeletal muscles, breathing exercises, training of the respiratory muscles using simulators and high-frequency chest wall oscillation.

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Abstract: Tuberculosis remains a threat to public health. The major problem for curing this disease is latent infection, of which the underlying mechanisms are still not fully understood. Previous studies indicate that natural killer (NK) cells do not play a role in inhibiting the growth of Mycobacterium tuberculosis in the lung, and recent studies have revealed that NK cells regulate the adaptive immunity during mycobacterial infection. By using a mouse model of direct lung infection with Mycobacterium bovis bacillus Calmette‐Guerin (BCG), we found that the presence of NK cells postponed the priming and activation of T cells after BCG infection. In addition, depletion of NK cells before infection alleviated pulmonary pathology. Further studies showed that NK cells lysed BCG‐infected macrophages in an NKG2D dependent manner. Thus, NK cells did not play a direct role in control BCG, but aggravated the pulmonary inflammation and impaired anti‐BCG T cell immunity, likely through killing BCG‐infected macrophages. Our results may have important implications for the design of immune therapy to treat tuberculosis. [ABSTRACT FROM AUTHOR]