Autopsy Findings of Severe COVID-19 Pneumonia Combined with Pulmonary Aspergillosis, Pneumothorax, and Pulmonary Thromboembolisms.

BACKGROUND COVID-19-associated pulmonary aspergillosis (CAPA), acute respiratory distress syndrome (ARDS), pulmonary thromboembolism (PTE), and pneumothorax are complications in severe COVID-19 patients. CASE REPORT A 64-year-old Japanese man was diagnosed with COVID-19. His past medical history included uncontrolled diabetes mellitus. He had no vaccination for COVID-19. Despite oxygen inhalation, remdesivir, dexamethasone (6.6 mg per day), and baricitinib (4 mg per day for 12 days), the disease progressed. The patient was supported with mechanical ventilation. Dexamethasone was switched to methylprednisolone (1000 mg per day for 3 days, and then reduced by half every 3 days), and intravenous heparin was initiated. Voriconazole (800 mg on the first day and then 400 mg per day for 14 days) was also started because Aspergillus fumigatus was detected in intratracheal sputum. However, he died of respiratory failure. Pathological findings of autopsy showed: (1) diffuse alveolar damage in a wide area of the lungs, which is consistent with ARDS due to COVID-19 pneumonia, (2) PTEs in peripheral pulmonary arteries, (3) CAPA, and (4) pneumothorax induced by CAPA. These conditions were all active states, suggesting that the treatments were insufficient. CONCLUSIONS Autopsy revealed active findings of ARDS, PTEs, and CAPA in a severe COVID-19 patient despite heavy treatment for each condition. CAPA can be a cause of pneumothorax. It is not easy to improve these conditions simultaneously because their treatments can induce antagonizing biological actions. To prevent severe COVID-19, it is important to reduce risk factors, such as by vaccination and appropriate blood glucose control.

A Case Series of Spontaneous Pneumomediastinum With/Without Pneumothorax in COVID-19.

With the previous worldwide initial coronavirus disease 2019 (COVID-19) pandemic, a notable rise in spontaneous pneumomediastinum with/without pneumothorax (SPP) has been noted. Most cases were initially reported as complications secondary to barotrauma from mechanical ventilation (MV) with COVID-19. However, with the Delta strain, starting from December 2020, there have been multiple reports of SPP. The SPP is an uncommon complication outside use of assisted ventilation with either noninvasive positive pressure ventilation (NIPPV) or MV. COVID-19 has been linked to higher incidence of SPP without use of NIPPV or MV. We present a series of 5 cases with a polymerase chain reaction-confirmed COVID-19 diagnostic testing whose hospital course was complicated by SPP unrelated to the use of either NIPPV or MV.

Management of pneumothorax: an update.

PURPOSE OF REVIEW: Pneumothorax is a global health problem. To date, there is still significant variation in the management of pneumothorax. For the past few years, there have been significant developments in the outpatient management of both primary and secondary spontaneous pneumothorax (SSP). We will review the latest evidence for the management of nontraumatic pneumothorax (spontaneous and iatrogenic) to include pneumothorax associated with COVID-19 infection. RECENT FINDINGS: Outpatient management of both primary and SSP may be safe and feasible. SUMMARY: Outpatient management of both primary and SSP should be included in treatment options discussion with patients.

Enhancing thoracic disease detection using chest X-rays from PubMed Central Open Access.

Large chest X-rays (CXR) datasets have been collected to train deep learning models to detect thorax pathology on CXR. However, most CXR datasets are from single-center studies and the collected pathologies are often imbalanced. The aim of this study was to automatically construct a public, weakly-labeled CXR database from articles in PubMed Central Open Access (PMC-OA) and to assess model performance on CXR pathology classification by using this database as additional training data. Our framework includes text extraction, CXR pathology verification, subfigure separation, and image modality classification. We have extensively validated the utility of the automatically generated image database on thoracic disease detection tasks, including Hernia, Lung Lesion, Pneumonia, and pneumothorax. We pick these diseases due to their historically poor performance in existing datasets: the NIH-CXR dataset (112,120 CXR) and the MIMIC-CXR dataset (243,324 CXR). We find that classifiers fine-tuned with additional PMC-CXR extracted by the proposed framework consistently and significantly achieved better performance than those without (e.g., Hernia: 0.9335 vs 0.9154; Lung Lesion: 0.7394 vs. 0.7207; Pneumonia: 0.7074 vs. 0.6709; Pneumothorax 0.8185 vs. 0.7517, all in AUC with p< 0.0001) for CXR pathology detection. In contrast to previous approaches that manually submit the medical images to the repository, our framework can automatically collect figures and their accompanied figure legends. Compared to previous studies, the proposed framework improved subfigure segmentation and incorporates our advanced self-developed NLP technique for CXR pathology verification. We hope it complements existing resources and improves our ability to make biomedical image data findable, accessible, interoperable, and reusable.

Hemoptysis after COVID-19 and the importance of differential diagnosis: Birt-Hogg-Dubé syndrome.

Birt-Hogg-Dubé syndrome is a genodermatosis of autosomal dominant inheritance characterized by mutations in the folliculin (FLCN) gene. There is an inappropriate inhibition/activation of a protein, the foliculin, which may cause tumor lesions in skin, renal and lung lesions; they could have more risk of developing pneumothorax compared to the normal population. A 38-year-old male patient with bronchial asthma who consulted for hemoptysis three weeks after recovery from COVID-19 infection. A chest tomography was requested, showing an air cyst in the left lower lobe. Physical examination shows evidence of thoracic skin lesions which a skin biopsy was performed on. The results were compatible with fibrofolliculoma. Differential diagnoses were proposed. A genetic disorder associated with skin lesions was suspected. A multi-genetic panel that includes BRCA1, BRCA2, TP53 and FLCN genes was requested, which reported the mutation of the FLCN gene in heterozygosis classified as pathognomonic of Birt-Hogg-Dubé syndrome. Patient is currently under clinical follow-up while genetic counseling was requested for relatives.

El síndrome de Birt-Hogg-Dubé es una genodermatosis de herencia autosómica dominante caracterizada por mutaciones en el gen foliculina (FLCN), donde existe inhibición/activación inapropiada de una proteína, la foliculina, que puede causar lesiones tumorales sistémicas, principalmente a nivel de la piel, renal y lesiones pulmonares, presentando mayor riesgo de desarrollar neumotórax en comparación con la población normal. Comunicamos el caso de un varón de 38 años con asma bronquial que consultó por hemoptisis 3 semanas después de la recuperación de la infección por COVID-19. Se solicitó una tomografía de tórax, que mostró un quiste aéreo en el lóbulo inferior izquierdo. Además, presentaba en el examen físico una lesión cutánea que fue biopsiada, presentando diagnóstico de foliculoma. Se plantearon diagnósticos diferenciales y ante la sospecha de probable desorden genético, un panel genético fue solicitado. Se confirmó síndrome de Birt-Hogg-Dubé ante el hallazgo de la deleción heterocigota que comprende el exón 1 del gen FLCN clasificada como patogénica. Actualmente el paciente se encuentra en seguimiento clínico mientras se solicitó estudio genético para familiares.

A Case of Pneumothorax Ex Vacuo Associated with COVID-19.

Pneumothorax is a known complication of coronavirus disease 2019 (COVID-19). The concept of pneumothorax ex vacuo has also been proposed to describe pneumothorax that occurs after malignant pleural effusion drainage. Herein, we present the case of a 67-year-old woman who had abdominal distension for 2 months. A detailed examination led to the suspicion of an ovarian tumor and revealed an accumulation of pleural effusion and ascitic fluid. Thoracentesis was performed, raising the suspicion of metastasis of high-grade serous carcinoma arising from the ovary. An ovarian biopsy was scheduled to select subsequent pharmacotherapy, and a drain was inserted preoperatively into the left thoracic cavity. Thereafter, a polymerase chain reaction analysis revealed that the patient was positive for COVID-19. Thus, the surgery was postponed. After the thoracic cavity drain was removed, pneumothorax occurred, and mediastinal and subcutaneous emphysema was observed. Thoracic cavity drains were then placed again. The patient's condition was conservatively relieved without surgery. This patient may have developed pneumothorax ex vacuo during the course of a COVID-19 infection. Since chronic inflammation in the thoracic cavity is involved in the onset of pneumothorax ex vacuo, careful consideration is required for the thoracic cavity drainage of malignant pleural effusion and other fluid retention.

[Pulmonary cavitations, late complication of COVID-19].

Patients who have recently suffered from SARS-CoV-2 infections may suffer serious complications, such as pneumothorax or pulmonary cavitations that increase morbi-mortality and imply a challenge for the design of the most appropriate therapeutic strategy to improve their prognosis. Pulmonary cavities are usually associated with secondary complications such as hemoptysis and pneumothorax, and so offer a poor prognosis. We present the case of two patients with COVID-19 disease confirmed by nasopharyngeal PCR who showed satisfactory evolution before readmission with pulmonary involvement compatible with pulmonary cavitation and respiratory failure. Cavitated lesions in the lungs of patients who recently suffered COVID-19 must be identified early in order to discard additional superinfections that may worsen the prognosis.

Spontaneous pneumothorax associated with COVID-19 pneumonia: a single-centre retrospective study.

Spontaneous pneumothorax (SP) is a rare complication of COVID-19 pneumonia; it affects both intubated and non-intubated patients. The pathogenesis includes barotrauma and pneumatocele formation. In the following article, we present case series of 18 patients with COVID-19 associated pneumothorax - a detailed demographic and clinical analysis were performed. The study revealed that men were more affected than women, especially above the age of 55 years; whilst, the distribution of intubated patients and those with spontaneous breathing were equal. Importantly, tube thoracostomy was the preferred method of treatment. The lethal outcome was observed in all patients on mechanical ventilation, due to the severe course of the underlying disease. The occurrence of pneumothorax in patients with COVID-19 is associated with poorer outcome of the disease, especially in those placed on mechanical ventilation.

Full medical treatment of COVID-19 associated large pneumothorax - A case report.

A 52-year-old man was re-admitted two weeks after recovering from severe COVD-19 following a 3-days history of cough and worsening shortness of breath. The chest radiograph showed a large right-sided pneumothorax. The first attempt at drainage, performed through a large bored tube, failed. Due to the large dimension of the pneumothorax, and the lung condition (extensive consolidation and diffuse bullous dystrophies), the only thoracic surgical approach prospected was a pneumonectomy. Willing to preserve the lung, the pulmonology team attempted a multi-phase medical-oriented strategy based on medical thoracoscopy. Therefore, the patient underwent 5 chest tube insertions, 2 talc pleurodesis, and an intrapleural blood patch. Air leakage resolution was progressively achieved, and the patient became asymptomatic.

Tension pneumothorax in a patient with Covid-19 pneumonia initially misdiagnosed as volvulus.

Tension pneumothorax is a condition that can present with a myriad of symptoms, including chest pain, shortness of breath, rapid breathing, and tachycardia. If left untreated, these signs and symptoms can progress to shock causing haemodynamic collapse and even death. At times, it may be difficult to identify tension pneumothorax. We present the case of a 59-year-old male with a prolonged initial hospital course that eventually led to a diagnosis of tension pneumothorax with the use of CT scans rather than traditional X-rays. This case reinforces the idea that clinicians should have a wide differential diagnosis in mind when dealing with vague symptoms and should not hesitate to use different diagnostic modalities to help confirm a diagnosis.

Risk factors of pneumothorax and pneumomediastinum in COVID-19: a matched case-control study.

BACKGROUND: During the novel coronavirus disease-2019 pandemic, a considerable number of pneumothorax (PNX)/pneumomediastinum (PNM) associated with COVID-19 have been reported, and the incidence is higher in critically ill patients. Despite using a protective ventilation strategy, PNX/PNM still occurs in patients on invasive mechanical ventilation (IMV). This matched case-control study aims to identify the risk factors and clinical characteristics of PNX/PNM in COVID-19. METHODS: This retrospective study enrolled adult patients with COVID-19, admitted to a critical care unit from March 1, 2020, to January 31, 2022. COVID-19 patients with PNX/PNM were compared, in a 1-2 ratio, to COVID-19 patients without PNX/PNM, matched for age, gender, and worst National Institute of Allergy and Infectious Diseases ordinal scale. Conditional logistic regression analysis was performed to assess the risk factors for PNX/PNM in COVID-19. RESULTS: 427 patients with COVID-19 were admitted during the period, and 24 patients were diagnosed with PNX/PNM. Body mass index (BMI) was significantly lower in the case group (22.8 kg/m2 and 24.7 kg/m2; P = 0.048). BMI was statistically significant risk factor for PNX/PNM in univariate conditional logistic regression analysis [odds ratio (OR), 0.85; confidence interval (CI), 0.72-0.996; P = 0.044]. For patients on IMV support, univariate conditional logistic regression analysis showed the statistical significance of the duration from symptom onset to intubation (OR, 1.14; CI, 1.006-1.293; P = 0.041). CONCLUSIONS: Higher BMI tended to show a protective effect against PNX/PNM due to COVID-19 and delayed application of IMV might be a contributive factor for this complication.

Time dependency and unique etiology of barotrauma in COVID-19: A retrospective cohort study with landmark analysis and pathological approach.

BACKGROUND: Barotrauma frequently occurs in coronavirus disease 2019. Previous studies have reported barotrauma to be a mortality-risk factor; however, its time-dependent nature and pathophysiology are not elucidated. To investigate the time-dependent characteristics and the etiology of coronavirus disease 2019-related-barotrauma. METHODS AND FINDINGS: We retrospectively reviewed intubated patients with coronavirus disease 2019 from March 2020 to May 2021. We compared the 90-day survival between the barotrauma and non-barotrauma groups and performed landmark analyses on days 7, 14, 21, and 28. Barotrauma within seven days before the landmark was defined as the exposure. Additionally, we evaluated surgically treated cases of coronavirus disease 2019-related pneumothorax. We included 192 patients. Barotrauma developed in 44 patients (22.9%). The barotrauma group's 90-day survival rate was significantly worse (47.7% vs. 82.4%, p < 0.001). In the 7-day landmark analysis, there was no significant difference (75.0% vs. 75.7%, p = 0.79). Contrastingly, in the 14-, 21-, and 28-day landmark analyses, the barotrauma group's survival rates were significantly worse (14-day: 41.7% vs. 69.1%, p = 0.044; 21-day: 16.7% vs. 62.5%, p = 0.014; 28-day: 20.0% vs. 66.7%, p = 0.018). Pathological examination revealed a subpleural hematoma and pulmonary cyst with heterogenous lung inflammation. CONCLUSIONS: Barotrauma was a poor prognostic factor for coronavirus disease 2019, especially in the late phase. Heterogenous inflammation may be a key finding in its mechanism. Barotrauma is a potentially important sign of lung destruction.

Pneumothorax in hospitalized COVID-19 patients with severe respiratory failure: Risk factors and outcome.

PNX was described as an uncommon complication in COVID-19 patients but clinical risk predictors and the potential role in patient's outcome are still unclear. We assessed prevalence, risk predictors and mortality of PNX in hospitalized COVID- 19 with severe respiratory failure performing a retrospective observational analysis of 184 patients admitted to our COVID-19 Respiratory Unit in Vercelli from October 2020 to March 2021. We compared patients with and without PNX reporting prevalence, clinical and radiological features, comorbidities, and outcomes. Prevalence of PNX was 8.1% and mortality was >86% (13/15) significantly higher than in patients without PNX (56/169) (P < 0.001). PNX was more likely to occur in patients with a history of cognitive decline (HR: 31.18) who received non-invasive ventilation (NIV) (p < 0.0071) and with low P/F ratio (HR: 0.99, p = 0.004). Blood chemistry in the PNX subgroup compared to patients without PNX showed a significant increase in LDH (420 U/L vs 345 U/L, respectively p = 0.003), ferritin (1111 mg/dl vs 660 mg/dl, respectively p = 0.006) and decreased lymphocytes (HR: 4.440, p = 0.004). PNX may be associated with a worse prognosis in terms of mortality in COVID patients. Possible mechanisms may include the hyperinflammatory status associated with critical illness, the use of NIV, the severity of respiratory failure and cognitive impairment. We suggest, in selected patients showing low P/F ratio, cognitive impairment and metabolic cytokine storm, an early treatment of systemic inflammation in association with high-flow oxygen therapy as a safer alternative to NIV in order to avoid fatalities connected with PNX.

The Macklin effect closely correlates with pneumomediastinum in acutely ill intubated patients with COVID-19 infection.

PURPOSE: Patients with COVID-19 infection are frequently found to have pulmonary barotrauma. Recent work has identified the Macklin effect as a radiographic sign that often occurs in patients with COVID-19 and may correlate with barotrauma. METHODS: We evaluated chest CT scans in COVID-19 positive mechanically ventilated patients for the Macklin effect and any type of pulmonary barotrauma. Patient charts were reviewed to identify demographic and clinical characteristics. RESULTS: The Macklin effect on chest CT scan was identified in a total of 10/75 (13.3%) COVID-19 positive mechanically ventilated patients; 9 developed barotrauma. Patients with the Macklin effect on chest CT scan had a 90% rate of pneumomediastinum (p < 0.001) and a trend toward a higher rate of pneumothorax (60%, p = 0.09). Pneumothorax was most frequently omolateral to the site of the Macklin effect (83.3%). CONCLUSION: The Macklin effect may be a strong radiographic biomarker for pulmonary barotrauma, most strongly correlating with pneumomediastinum. Studies in ARDS patients without COVID-19 are needed to validate this sign in a broader population. If validated in a broad population, future critical care treatment algorithms may include the Macklin sign for clinical decision making and prognostication.

Imaging in the Intensive Care Unit.

Radiology plays an important role in the management of the most seriously ill patients in the hospital. Over the years, continued advances in imaging technology have contributed to an improvement in patient care. However, even with such advances, the portable chest radiograph (CXR) remains one of the most commonly requested radiographic examinations. While they provide valuable information, CXRs remain relatively insensitive at revealing abnormalities and are often nonspecific. Chest computed tomography (CT) can display findings that are occult on CXR and is particularly useful at identifying and characterizing pleural effusions, detecting barotrauma including small pneumothoraces, distinguishing pneumonia from atelectasis, and revealing unsuspected or additional abnormalities which could result in increased morbidity and mortality if left untreated. CT pulmonary angiography is the modality of choice in the evaluation of pulmonary emboli which can complicate the hospital course of the ICU patient. This article will provide guidance for interpretation of CXR and thoracic CT images, discuss some of the invasive devices routinely used, and review the radiologic manifestations of common pathologic disease states encountered in ICU patients. In addition, imaging findings and complications of more specific clinical scenarios in which the incidence has increased in the ICU setting, such as patients who are immunocompromised, have interstitial lung disease, or COVID-19, will also be discussed. Communication between the radiologist and intensivist, particularly on complicated cases, is important to help increase diagnostic accuracy and leads to an improvement in the management of the most critically ill patients.

Spontaneous pneumothorax in COVID-19: a single center experience.

OBJECTIVE: The effect of pulmonary complications of COVID-19, such as pneumothorax, pneumomediastinum, and subcutaneous emphysema, is still unclear. This study aimed at investigating the relationship between COVID-19 and spontaneous pneumothorax. PATIENTS AND METHODS: This study was conducted as a single-center retrospective study. Groups were assigned as study and control groups. The study group (n=120) included patients who were followed up in ICU and developed pneumothorax during their follow-up. The control group (n=120) included patients who did not develop a pneumothorax in ICU and who had been randomly selected using hospital records. Demographic findings, laboratory parameters, radiological findings, clinical management, patients' follow-up patterns, and survival status of the patients were recorded. RESULTS: There was a significant relationship between gender, outcome, last hospitalization, general condition, first follow-up, intubation, uptake tomography, uptake rate, CO-RADS, and involvement variables between groups (p<0.05). In the survival analysis performed in the control and study groups, a significant difference was obtained between the averages of the two groups (LogRank=3.944, p<0.05). Intubation and mortality rates of the patients who developed pneumothorax during the patient follow-ups were significantly higher than the control group. CONCLUSIONS: We found that patients diagnosed with COVID-19 who developed pneumothorax during intensive care follow-up had a higher hospital stay and intubation rate. The pneumothorax rate was also higher in follow-up methods such as noninvasive/HFO providing PEEP to the patients. The data in our study may help reducing mortality by shedding light on the early prevention and recognition of pneumothorax in critically ill patients diagnosed with COVID-19.

The relationship between mortality and inflammatory markers and the systemic immune inflammatory index in patients in the intensive care unit with a pneumothorax as a complication of COVID-19 disease.

BACKGROUND: A pneumothorax is common in patients admitted to the intensive care unit (ICU) with coronavirus disease (COVID-19) when non-invasive or invasive mechanical ventilation is performed to maintain adequate oxygenation. The aim of the present study was to investigate the effects of elevated inflammatory markers and an elevated systemic immune inflammatory index (SII) on mortality in this patient population. MATERIALS AND METHODS: Between March 2020 and May 2021, 124 patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reacion positviity who were admitted to the ICU in our hospital and diagnosed with and treated for a pneumothorax were evaluated retrospectively. Interleukin-6 (IL-6), C-reactive protein, neutrophil, lymphocyte, platelet and white blood cell levels were measured. These parameters were used to calculate the neutrophil-lymphocyte ratio (NLR) and SII, and the association of these parameters with pneumothorax-related mortality was examined. RESULTS: This study included 39 female (31.5%) and 85 male (68.5%) patients. The mean age was 65.3 ± 12.6 years. Non-invasive mechanical ventilation was performed in 13 (10.5%) patients, and 111 (89.5%) patients received invasive mechanical ventilation. Tube thoracostomy was performed in 113 patients (91.1%), and 11 patients (8.9%) were treated with oxygen therapy. The factors affecting mortality in the pneumothorax patients were the Charlson Comorbidity Index (four or higher), IL-6 level and NLR. The IL-6 level was 53.4 in those who died versus 24.6 in those who survived (p = 0.017). The NLR in the patients who died was 16.9 as compared to 12.5 in those who survived (p = 0.011). CONCLUSION: Elevated markers of infection were associated with an increased risk of mortality in pneumothorax patients with COVID-19 who received invasive or non-invasive mechanical ventilation in the ICU. In this patient population, high levels of positive end-expiratory pressure should be avoided, and inflammatory marker levels and the SII should be closely monitored.

Malignus pleuralis effusiókkal küzdo betegek ellátása egy regionális onkológiai központban a COVID-19-pandémia idoszakában.

INTRODUCTION: Malignant pleural effusion is a complication of tumors heralding poor outcome. It may be life-threatening, so advanced cases should be treated as an oncological emergency. OBJECTIVE: We aimed to provide complex care to patients with malignant pleural effusion during the COVID-19 pandemic at the University of Pécs Medical School, in the Department of Oncotherapy. During the pandemic, we introduced the thoracocentesis as a routine method in our department without previous experiences. METHOD: Results of diagnosing and treating pleural effusion of patients between March 18th of 2020 and May 31st of 2021 were summarized. RESULTS: We have analyzed data of 45 patients, two-thirds (66.7%) of them were women, the median age was 67 years. 57.8% of patients received systemic anticancer therapy during the study. The total number of thoracocentesis was over 120, one-third of the patients required more than five interventions. Only three iatrogenic pneumothorax cases were detected, no other serious complications were experienced. The procedures - that were aimed to mitigate symptoms in most cases (80%) - were considered successful. However, 48.9% of the patients were no longer alive at the end of the study period indicating very poor prognosis of pleural carcinosis. DISCUSSION AND CONCLUSION: Clinical care of oncological patients was continuous during the pandemic; patients treated as part of emergency care were often seen in advanced disease state. Treatment of malignant pleural effusion requires oncological foresight as well as implementing an invasive approach. Our study has shown that discussion of the topic is relevant, may reveal difficulties and need for improvement. Our results are consistent with literature data, we have experienced less complications than reported in the literature. Orv Hetil. 2022; 163(26): 1015-1022.