Citations

Background: Currently, biomarkers do not have a role in diagnosis or outcome prediction models for patients with recurrent anterior shoulder instability. Purpose/Hypothesis: The purpose of this study was to compare gene expression differences in the blood and tissue of patients with anterior shoulder instability with and without significant glenoid bone loss (GBL). The hypothesis was that the severity of GBL would be associated with the expression level of genes in the blood and capsular tissue of patients with anterior shoulder instability. Study Design: Descriptive laboratory study. Methods: Consecutive patients with anterior shoulder instability undergoing arthroscopic and open shoulder stabilization were prospectively enrolled. Blood and anterior capsular tissue specimens obtained during surgery were compared between patients with significant GBL (≥10%) and patients without significant GBL (<10%). RNA was extracted, and a panel of 277 inflammatory genes was utilized to quantify gene expression at the RNA level using a probe-based RNA quantification platform. Differential expression analysis was performed to identify genes expressed at different levels between patients with and without significant GBL. The expression levels of the subset of genes identified were used to generate a ridge regression model to predict the severity of GBL. Quantitative polymerase chain reaction was performed to confirm probe-based RNA findings. Results: A total of 17 patients were included, with a mean age of 26 years. Overall, 7 patients had <10% GBL (mean, 2.3%), and 10 patients had ≥10% GBL (mean, 16.4%). There were 9 genes that were identified as significantly differentially expressed in the blood, and 5 of these ( IFIT1 , IFIT3 , IFI44 , PRKCB , and OAS2 with P values of 1 × 10 −5 , 1 × 10 −4 , 1 × 10 −4 , 1 × 10 −4 , and 6 × 10 −4 , respectively) were confirmed using nonparametric tests. The authors developed a model using the 5 genes to predict the severity of GBL, and this had an accuracy of 88% (95% CI, 64%-99%). By quantitative polymerase chain reaction, IFIT3 was confirmed to be significantly differentially expressed ( P = .012). Conclusion: There were significant gene expression differences in the blood of patients with (≥10%) and without (<10%) significant GBL. The differential expression of 5 genes allowed for the development of an accurate predictive model and transcriptomic biomarker to predict the severity of GBL. Clinical Relevance: The addition of a blood biomarker to current outcome prediction models may provide increased accuracy in identifying those at risk of failure from arthroscopic Bankart repair.

Abstract Introduction: Erdheim-Chester disease (ECD) is an exceptionally rare non-Langerhans cell histiocytic malignant disorder but presents a unique diagnostic challenge due to its diverse clinical manifestations from mild symptoms to severe, life-threatening multiorgan disease. Here, we report a case of ECD that presented with pleuro-pulmonary and vascular involvement rather than skeletal lesions. Case description: A 75-year-old man with a history of systemic lupus erythematosus, rheumatoid arthritis, and chronic obstructive pulmonary disease presented with syncope, anorexia, fatigue, and weight loss. He was noted to be in atrial fibrillation. Subsequent imaging studies, including. The CTA of chest and PET-CT scans showed hyperdense wall thickening in multiple arteries and veins, including the pulmonary arteries and veins, aortic arch, thoracic and abdominal aorta, and iliac arteries as well as pulmonary nodules suggestive of a large vessel vasculitis associated with systemic inflammation. The patient underwent a pleural biopsy which only demonstrated nonspecific inflammation. He subsequently underwent surgical wedge biopsy of a superior right lower lobe and multiple pleural biopsies showed atypical histiocytic infiltrate suspicious for a histoplasmic neoplasm with the atypical histiocytes characterized by plump to spindled nuclei with focal emperipolesis. Atypical histiocytes were positive for CD163, factor 13a, cyclin D1 suggestive of ECD. As further testing demonstrated a negative BRAFV600E mutation, the patient was initiated on cobimetinib 40 mg daily. He responded to therapy with subjective and objective improvement. There has been no radiographic evidence of recurrence. Discussion: The diagnosis of ECD relies on clinical presentation, imaging studies, and distinctive pathological findings. Overall, the prognosis depends on the degree of histiocytic damage before initiation of treatment; degree of inflammation; age; digestive tract involvement. A biopsy revealing non-Langerhans cell histiocytosis, supported by immunohistochemistry exams, is essential for confirming the diagnosis. Diagnosing ECD is challenging due to its rarity and multisystem involvement necessitating a multidisciplinary approach. Pulmonary involvement, seen in 43% of cases, often presents with features of interstitial lung disease but does not significantly impact overall prognosis. Recent evidence implicates the BRAFV600E mutation in ECD pathogenesis, suggesting new therapeutic possibilities.

Abstract IntroductionFungal infections, particularly in the Midwest, can often be asymptomatic and may mimic primary lung cancer. This case illustrates pulmonary histoplasmosis in an 80-year-old woman with a history of lung cancer highlighting the diagnostic challenges presented when both conditions coexist.Case SummaryAn 80-year-old woman (prior smoking history of 47-pack-years) with synchronous lung cancers (poorly differentiated non-small cell carcinoma with squamous differentiation in the left lower lobe and squamous cell carcinoma in the right lower lobe) previously underwent radiation therapy to both lesions. She was admitted for shortness of breath and cough and was initially diagnosed with pneumonia based on CT findings. Despite multiple courses of antibiotics, her symptoms persisted over 2 months, improving only temporarily with a short course of prednisone. A follow-up CT revealed increasing confluent thick-walled cavitation in the posterior right upper lobe and superior segment of the right lower lobe concerning for cavitating/necrotizing pneumonia versus possible cancer progression. A PET-CT scan (Fig.1A) showed significant FDG uptake in the right upper lobe lesion and mild uptake in mediastinal lymph nodes complicating the differentiation between cancer and infection. Bronchoscopy with biopsy of an endobronchial lesion in the posterior segment of right lower lobe revealed necrotizing granulomatous inflammation (Fig.1B) with GMS stain showing the presence of fungal organisms suggestive of histoplasmosis. Histoplasma PCR from bronchoalveolar lavage was also positive. She was subsequently started on antifungal therapy for a planned one-year treatment course. DiscussionHigh positron emission tomography (PET) avidity in chest imaging is often linked to aggressive tumors but can also indicate benign conditions such as fungal infections. A “flip-flop sign” on PET imaging, where nodal activity surpasses that of a lung nodule, is typically seen in benign lung lesions, particularly fungal infections. However, infections and inflammatory conditions may also show high PET avidity mimicking malignancy. Endobronchial lesions, common in lung cancer, are less frequently associated with infections. In patients with a history of cancer, active lung infection, and PET-avid lesions without the flip-flop sign, invasive testing is usually required to differentiate between infection and malignancy. In this case, our patient with a history of lung cancer and a PET-avid lung lesion was found to have pulmonary histoplasmosis after invasive testing highlighting the need for comprehensive evaluation.ConclusionThis case emphasizes the importance of considering fungal infections in the differential diagnosis of PET-avid pulmonary lesions, particularly in patients with a history of malignancy.

Abstract Fibrosing mediastinitis is an infiltrative disease which may develop secondary to a variety of causes, including autoimmune, infectious, and malignant processes. Here, we present a case of fibrosing mediastinitis, with initial concerns for IgG4-related disease. A 36-year-old man presented to his primary provider with three months of intermittent dyspnea. CT chest was significant for a large, infiltrative mediastinal and left hilar mass with calcifications and involvement of the left upper and lower lobe bronchi, lingular bronchus, and left main pulmonary artery. Subsequent autoimmune and fungal studies were negative. The patient underwent bronchoscopy, with biopsy of a lymph node at station 11L showing increased IgG4 on immunostain (30 cells/hpf), though IgG immunostaining was not completed for comparison. Despite initial concerns for fibrosing mediastinitis, the patient was diagnosed with IgG4-related disease and initiated on rituximab and mycophenolate. Notably, the patient's serum IgG4 concentrations were consistently within normal limits before and after initiation of rituximab. The patient was referred to our clinic after lack of response to therapy on imaging. Laboratory evaluation redemonstrated a normal serum IgG4 concentration and fungal studies were consistent with previous histoplasma infection, suggesting fibrosing mediastinitis secondary to histoplasmosis. IgG4-related disease was determined to be unlikely considering repeatedly normal IgG4 levels and weakly positive IgG4 staining. Repeat CT chest demonstrated fibrosis of the left upper lobe; compression of the left atrial appendage; and occlusion and severe obstruction of the left superior pulmonary vein and left lower lobe pulmonary artery, respectively. VQ scan demonstrated significantly reduced perfusion of the left lung and the patient was referred for stenting of the affected vasculature. PET-CT revealed moderate FDG avidity of the left hilar nodes, concerning for ongoing active fibrosing mediastinitis, for which he was continued on rituximab. The indolent nature of fibrosing mediastinitis often leads to advanced disease at the time of presentation. Hilar structures are commonly involved, as in the case of this patient with a severe perfusion defect secondary to obstruction of the pulmonary vessels. A diagnosis of fibrosing mediastinitis merits careful investigation of the underlying cause. Fungal infections, specifically histoplasmosis in North America, are a leading cause of this condition. IgG4-related disease is also associated with fibrosing mediastinitis, and both conditions are driven by fibroinflammatory processes. However, it is important to note that IgG4 immunostaining is non-specific, and diagnosis of IgG4-related disease requires the meeting of rigorous criteria. Differentiation between these diagnoses is important given potential differences in management.

Abstract Introduction: Birt-Hogg-Dube (BHD) is a rare autosomal dominant genetic disorder caused by mutations in the FLCN tumor suppressor gene. Clinically, BHD is characterized by development of cutaneous fibrofolliculomas/trichodiscomas, renal tumors, and pulmonary cysts, the latter which can result in recurrent, spontaneous pneumothoraces. We present a case of BHD in which diagnosis was delayed given absence of dermatologic and renal manifestations. Case Report: A 66-year-old female never smoker with a past medical history of left-sided breast cancer treated with lumpectomy and chemoradiation and osteoporosis presented for evaluation of recurrent pneumothoraces. Her first pneumothoraces occurred in her 20s-30s and required doxycycline pleurodesis (right side) and video-assisted thoracoscopic pleurodesis (left side). The most recent pneumothorax was in her 50s and resolved with chest tube placement. She reported repeated episodes of pneumonia which prompted pulmonary re-evaluation. A non-contrast CT chest was obtained which demonstrated middle and lower lobe predominant irregular thin-walled cystic changes with paramediastinal involvement. Pulmonary function testing revealed mild hyperinflation but otherwise no evidence of obstruction, restriction, or diffusion limitations (FEV1 113% predicted, FEV1/FVC of 0.72 predicted, FVC 109% predicted, TLC 108% predicted, DLCO 90% predicted). Immunoglobulins and alpha-1 antitrypsin were obtained and normal. A lung biopsy was discussed for definitive diagnosis but never performed. Upon presentation to our clinic, she reported no symptoms such as cough, shortness of breath, pleuritic chest pain, fevers, arthralgias, myalgias, rashes, dry mouth, or dry eyes. A broad differential was considered and a connective tissue disease cascade, VEGF-D testing, and SPEP/UPEP were sent and negative/normal. Given the distribution of cysts on her CT, BHD was considered, and she was referred to clinical genetics for germline testing which identified a heterozygous FLCN variant (c.837dup, p.Glu280Argfs[asterisk]12) consistent with BHD. Discussion: BHD is a rare and underdiagnosed cause of cystic lung disease as it has a broad range of clinical manifestations. Recognizing the disease without either renal or dermatologic manifestations as in our patient can be challenging and requires a high degree of suspicion. Clues to the diagnosis include a family history of spontaneous pneumothorax, which can be highly predictive of BHD as it is the most common cause of hereditary pneumothorax. Definitive diagnosis of BHD depends on a combination of clinical features and germline testing for mutations in the FLCN gene.

Abstract Obstructive shock is rare, occurring in 2% of patients admitted to the intensive care unit (ICU) with shock. Understanding the unique pathophysiology of obstructive shock can aid in resuscitation efforts and significantly impact patient outcomes. Our goal is to expand the current understanding of possible shock etiologies and the treatment of obstructive shock. We present a case of an 88-year-old woman presenting to the ICU following an out-of-hospital cardiac arrest. Family found her unresponsive, called EMS, and started CPR. Upon EMS arrival, she had a pulse; the rhythm was identified as atrial fibrillation. She was cardioverted and transferred to the emergency room. Upon admission, she was intubated and sedated but hemodynamically stable. Shortly after arrival, she developed refractory shock requiring volume resuscitation and rapid titration of three vasoactive medications. She intermittently responded to volume but quickly developed recurrent shock following infusion completion. Bedside ultrasound showed collapse of the right atrium with a pericardial effusion and hyperechoic mobile mass within the pericardial space. Cardiology was called to the bedside for further evaluation of possible cardiac tamponade. There was lack of consensus regarding need for pericardiocentesis. Therefore, further chest imaging was ordered. CTA chest was negative for pulmonary emboli but showed a large hematoma in the anterior mediastinum with active bleeding. Formal echocardiogram confirmed a large extracardiac mass with extrinsic compression of the right atrium as well as a small-moderate circumferential pericardial effusion without obvious features of tamponade. She underwent an urgent IR angiogram with embolization of the internal mammary artery and placement of a 14F locking loop pigtail catheter into the anterior mediastinal hematoma felt to be contained within a known 3.5 cm benign cystic lesion. She experienced significant hemodynamic improvement following embolization and drain placement. The etiology of her presumed PEA arrest remained unclear, though it was concluded that the obstructive shock was due to the anterior mediastinal hematoma, a consequence of CPR. In this case we highlight the risk of arterial hemorrhage following resuscitation for cardiac arrest and the role it can play in the development of obstructive shock. There have been some documented cases of pericardial bleeding and the development of cardiac tamponade but limited case reports regarding arterial hemorrhage following CPR. Quickly identifying extracardiac compression allowed for appropriate and rapid IR embolization which led to clinical improvement in our patient.

Abstract Introduction: Lung cancer is the most frequently diagnosed cancer and leading cause of cancer death worldwide. While adenocarcinoma is the most common subtype of lung cancer, invasive mucinous adenocarcinoma (IMA) only represents an estimated 2-5% of lung adenocarcinomas. IMA has an incidence of just 0.2% among primary lung cancer patients. This rare form of lung cancer provides a significant diagnostic challenge due to its varied clinical and radiological manifestations, often exhibiting features overlapping with pneumonia. We present a case of IMA with radiographic findings of numerous cavitary nodules, an uncommon morphology reported in 3.5% of cases of IMA, originally thought to represent atypical multifocal pneumonia. Description of Case: A 76-year-old man with a history of coronary artery disease status post percutaneous coronary intervention on dual antiplatelet therapy; hypertension; chronic kidney disease; and 40 pack-year smoking history presented to primary care with 6 weeks of worsening cough productive of clear sputum and shortness of breath. He denied a history of fevers, night sweats, unintentional weight loss, recent travel, or sick contacts. A chest x-ray revealed extensive nodular parenchymal opacities in the lower lobes bilaterally concerning for multifocal pneumonia. Subsequent CT chest showed numerous bilateral, poorly-defined nodules with irregular margins and cavitary lesions. He was admitted for acute hypoxic respiratory failure in the setting of presumed atypical multifocal pneumonia. He completed a course of vancomycin and piperacillin/tazobactam. Notably, bronchoscopy with bronchoalveolar lavage and cytology were negative for infection and malignancy, respectively. Additional noninvasive infectious and inflammatory workup was negative and he was ultimately discharged. He was then readmitted to the ICU for respiratory failure where he eventually underwent transbronchial biopsy. Tissue biopsy revealed moderately-differentiated adenocarcinoma with mucinous features. PD-L1 staining was 0%. Genetic testing revealed two separate TP53 mutations, a KRAS G12D mutation, and SMAD4 alteration. Chemotherapy with carboplatin and pemetrexed was initiated inpatient. He had objective and subjective improvement and was ultimately discharged to continue treatment in the outpatient setting. Discussion: This case represents an uncommon presentation of an already rare form of lung cancer underscoring the diagnostic difficulty in the setting of overlapping clinical and radiological manifestations. Clinicians must consider malignancy when a patient with presumed pneumonia is not improving despite antibiotics. Bronchoscopy with both BAL and transbronchial biopsy is often required to make the diagnosis and exclude other etiologies. Early consideration of alternative diagnoses can improve patient outcomes and help avoid progressive respiratory failure.

Abstract Rationale: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of cancer. They are also associated with life-threatening immune-related adverse events (irAEs), including the rare, poorly understood, and potentially fatal triad of myasthenia gravis, myocarditis, and myositis(triple M syndrome). We aimed to describe the management, intensive care unit (ICU)utilization, and outcomes of patients with irAEs with a specific focus on triple M syndrome. Methods: We conducted a retrospective chart review of patients with irAEs admitted to three quaternary care hospitals between December 2018 and 2023. We aimed to collect data on demographics, cancer type, treatment, ICU resource utilization, and outcomes including mortality. Results: Over this 5-year period, 140 patients were admitted for irAEs. Forty-nine percent were male, median age was 73 (IQR 64-80) years, 7% were of African American or Asian descent, and 32%required ICU admission. Median ICU and hospital length of stay (LOS) were 1.5 (IQR 0.7-2.9)and 7.2 (IQR 4.1-13.4) days, respectively. Among ICU patients, 14/140 (10%) had myositis,22/140 (16%) myocarditis, and 9/140 (6.4%) myasthenia gravis. Triple-M syndrome was diagnosed in 7/140 (5%) patients, including 3 with metastatic melanoma, 2 with genitourinary malignancies, 1 with metastatic lung and 1 with colon cancer. Four had received pembrolizumab and 3 nivolumab. Median ICU and hospital LOS were 3 (IQR 1-6) and 10 (IQR 8-21) days in this group. Three patients required mechanical ventilation, one required tracheostomy, and one required vasopressor support. Triple-M management included corticosteroids, IVIG, pyridostigmine, mycophenolate mofetil, and rituximab. Patients with triple-M syndrome were significantly older than other patients with ICI toxicity (P &lt;0.009) and had higher mortality (57%vs 25%, p = 0.07). Patients discharged from the ICU had a median survival of 67 (IQR 26-201)days. Conclusions: Patients with irAEs frequently require ICU level of support with significant morbidity and mortality, especially with triple M syndrome. Clinicians should always consider the possibility of triple-M syndrome in patients with multiple irAEs as symptoms can be subtle and easily overlooked. Corticosteroids remain the primary treatment of irAEs and can be combined with other immunosuppressive agents such as infliximab, anti-thymocyte globulin, or pyridostigmine. Unfortunately, mortality due to triple-M syndrome remains high underscoring the importance of early recognition and prompt multidisciplinary management of these toxicities.

Abstract Introduction: Pulmonary sclerosing pneumocytoma, formerly known as sclerosing hemangioma, is an uncommon benign neoplasm most recently classified by the World Health Organization as an adenoma. It occurs most commonly in middle-aged women of East Asian descent, in whom it is most often discovered incidentally on imaging. It typically appears as a single, well-circumscribed lesion on CT that lacks specific defining characteristics and can appear similar to malignancies such as pulmonary adenocarcinoma. Therefore, diagnosis relies on histopathology. The tumor is derived from respiratory epithelial cells expressing TTF-1 in both round and surface cells, and immunohistochemistry (IHC) staining is positive for both TTF-1 and EMA. Description of Case: A 52-year-old female from Southeast Asia presented to primary care clinic reporting atypical chest pain. She denied shortness of breath, cough, fever, night sweats, or weight loss. She had no prior smoking history, but there was a remote history of chewing tobacco. Chest x-ray revealed a retrocardiac left lower lobe pulmonary nodule. CT chest was obtained and revealed a solid left lower lobe pulmonary nodule measuring 2.2 cm in diameter. The nodule was mildly FDG avid on subsequent PET-CT with SUVmax 2.8, noted to be suspicious for a lesion on the pulmonary adenocarcinoma spectrum. She opted for surgical removal and underwent thoracoscopic left lower lobe wedge resection. Pathology demonstrated sclerosing pneumocytoma with IHC stains positive for TTF1, EMA, and keratin AE1/AE3. The follow-up CT chest showed no evidence of local recurrence or residual tumor. Discussion: Pulmonary sclerosing pneumocytoma is an uncommon benign neoplasm of the lung that can be easily mistaken for malignancy such as pulmonary adenocarcinoma given its imaging characteristics and FDG avidity on PET-CT. It must be considered in the differential for lung nodules, particularly in middle-aged women of East Asian descent. Diagnosis is made with biopsy showing both cuboidal surface cells and stromal round cells, with IHC staining positively for TTF-1 and EMA. However, these tumors remain difficult to diagnose in frozen section, small biopsies, and cytology, because they are easily mistaken for adenocarcinoma or carcinoid tumors. The clinical course is generally benign, but very rarely there is metastasis or recurrence.

Abstract Rationale Immune checkpoint inhibitors (ICI) have become standard care for many cancers. Their mechanism of action mediates immune related adverse events including ICI pneumonitis. Diagnosis of this is difficult to differentiate from infectious and radiation pneumonitis as it is a diagnosis of exclusion often requiring bronchoscopy and imaging interpreted by expert radiologists. This study investigates the use of CALIPER, a computer-aided lung informatics program, in identifying differences between Computed Tomography (CT) patterns in ICI, radiation, and infectious pneumonitis that may aid in diagnosis noninvasively. Methods CT images of ten patients with ICI pneumonitis, ten patients with infectious pneumonitis, and nine patients with radiation pneumonitis, all diagnosed by clinical expertise and evaluation with bronchoalveolar lavage, were analyzed with CALIPER. CALIPER classified each CT voxel into either vessel-related structures (VRS), normal, mild low-attenuation area (LAA), moderate LAA, severe LAA, reticular (R), honeycomb (HC) or ground-glass (GG) features. Each lung was divided into upper, middle, and lower lobes. Exploratory analyses explored the relationship between CALIPER components and diagnosis, comparing ICI and radiation pneumonitis with infectious pneumonitis. Diagnosis was analyzed using multinomial logistic regression adjusted for presence of pleural effusion. Additionally, diagnosis was assessed as infectious versus a pooled group of radiation and ICI pneumonitis and analyzed using logistic regression adjusted for pleural effusion. Due to the exploratory nature of analysis, no correction was applied for multiplicity of testing. Results Twenty-nine patients were analyzed. ICI pneumonitis patients had less moderate low attenuation in the left upper (p = 0.016) and middle peripheral lung (p = 0.038), and radiation pneumonitis patients had less moderate low attenuation in the left upper peripheral lung (p = 0.031). When comparing the pooled group of ICI and radiation pneumonitis images with infectious pneumonitis, there was more moderate LAA in left upper (0.012) and middle (0.034) peripheral lung in the pooled group compared to infectious pneumonitis. There was no association with VRS, GG, HC, R, mild, or severe LAA patterns. Conclusions Although areas of moderate low attenuation were more prevalent for infectious pneumonitis, these results taken in the context of low sample size, exploratory analysis, and lack of clinical reasoning to support these findings make them likely insignificant. Based on this limited exploratory analysis, it is unlikely that we can solely use CALIPER as noninvasive evaluation to differentiate radiation and ICI pneumonitis from infectious pneumonitis. This highlights the need for a more robust program to aid in noninvasive diagnosis.