Outcomes of Pleural Space Infections in Patients With Indwelling Pleural Catheters for Active Malignancies.

BACKGROUND: Pleural infections related to indwelling pleural catheters (IPCs) are an uncommon clinical problem. However, management decisions can be complex for patients with active malignancies due to their comorbidities and limited life expectancies. There are limited studies on the management of IPC-related infections, including whether to remove the IPC or use intrapleural fibrinolytics. METHODS: We conducted a retrospective cohort study of patients with active malignancies and IPC-related empyemas at our institution between January 1, 2005 and May 31, 2021. The primary outcome was to evaluate clinical outcomes in patients with malignant pleural effusions and IPC-related empyemas treated with intrapleural tissue plasminogen activator (tPA) and deoxyribonuclease (DNase) compared with those treated with tPA alone or no intrapleural fibrinolytic therapy. The secondary outcome evaluated was the incidence of bleeding complications. RESULTS: We identified 69 patients with a malignant pleural effusion and an IPC-related empyema. Twenty patients received tPA/DNase, 9 received tPA alone, and 40 were managed without fibrinolytics. Those treated with fibrinolytics were more likely to have their IPCs removed as part of the initial management strategy ( P =0.004). The rate of surgical intervention and mortality attributable to the empyema were not significantly different between treatment groups. There were no bleeding events in any group. CONCLUSION: In patients with IPC-related empyemas, we did not find significant differences in the rates of surgical intervention, empyema-related mortality, or bleeding complications in those treated with intrapleural tPA/DNase, tPA alone, or no fibrinolytics. More patients who received intrapleural fibrinolytics had their IPCs removed, which may have been due to selection bias.

Airway stenting for central airway obstruction: a review.

Central airway obstruction is a serious complication of various diseases, most often malignancy. Malignant etiologies include primary lung cancer as most common though metastases from various other cancers can obstruct the airways as well. Benign etiologies include inflammatory or fibrotic changes due to prior airway interventions (e.g., endotracheal intubation or tracheostomy) or specific autoimmune conditions. Different interventional modalities exist including various electrosurgical or mechanical debulking tools, though these are sometimes insufficient or contraindicated for the purpose of restoration of airway patency. The placement of stents is thus needed in certain particularly complex or refractory cases. Airway stenting requires careful patient selection and stent selection along with a thorough knowledge of relevant anatomy and procedural technique. Indeed, certain clinical presentations are better suited for stent placement and more likely to achieve a symptomatic benefit. Moreover, a variety of stents exist with each having different attributes that may better fit specific conditions. Complications must be managed properly as well. These include stent migration, granulation tissue formation, and stent-related infection which can have clinically significant consequences. In this review, we will discuss airway stenting for central airway obstruction with regard to these various subject areas as well as conclude with discussion of future research directions.

Giant Cell Arteritis as an Uncommon Cause of Chronic Cough: A Case Report.

BACKGROUND Chronic cough is a common medical concern. Giant cell arteritis (GCA) is an uncommon cause of chronic cough and is not usually suspected since symptoms can be non-specific. We present a case of chronic cough due to GCA in which symptoms were subtle but imaging was remarkable and clearly disclosed the diagnosis. CASE REPORT A 71-year-old woman presented to the pulmonary clinic with a concern of worsening cough for 4 months. She had been treated with proton pump inhibitor, intranasal steroids, and antibiotics, without improvement. Other symptoms were an occasional headache for the prior 5 months, but this had resolved. She had a history of early-stage breast and thyroid cancers, both of which were treated surgically several years earlier and were in remission. Results of a physical examination including flexible video laryngoscopy of the upper airway were completely normal. Laboratory investigations showed normal blood chemistries and blood cell counts. Her C-reactive protein level was 1 mg/L (upper limit of normal <10) but her erythrocyte sedimentation level was 121 mm/hr (upper limit of normal <30). A positron emission tomography (PET) scan was performed as surveillance for her prior cancers. This showed diffuse tracer uptake in the aorta as well as bilateral common carotid, subclavian, and common iliac arteries, revealing GCA as the underlying diagnosis. CONCLUSIONS Giant cell arteritis is a rare cause of chronic cough. Other symptoms can be subtle or non-specific as in our case, and a high index of suspicion is needed to obtain a temporal artery biopsy. In these cases, imaging adjuncts can provide a non-invasive diagnosis.

Spontaneous resolution of Mycobacterium kansasii presenting as a spiculated lung mass.

A 68-year old woman with a long smoking history underwent lung cancer screening by low-dose computed tomography. This detected a 3.0 cm spiculated mass in the left upper lobe. Transbronchial biopsy revealed necrotizing granulomatous inflammation and cultures grew Mycobacterium kansasii. Given lack of symptoms and concerns over drug toxicity, the patient declined antimicrobial therapy and she was monitored radiographically. Serial CT scans at six and twenty-two months showed progressive resolution of the mass. We present the first report of Mycobacterium kansasii presenting as a solitary lung nodule that spontaneously resolved without treatment.

Incidence and Location of Atelectasis Developed During Bronchoscopy Under General Anesthesia: The I-LOCATE Trial.

BACKGROUND: Despite the many advances in peripheral bronchoscopy, its diagnostic yield remains suboptimal. With the use of cone-beam CT imaging we have found atelectasis mimicking lung tumors or obscuring them when using radial-probe endobronchial ultrasound (RP-EBUS), but its incidence remains unknown. RESEARCH QUESTION: What are the incidence, anatomic location, and risk factors for developing atelectasis during bronchoscopy under general anesthesia? STUDY DESIGN AND METHODS: We performed a prospective observational study in which patients undergoing peripheral bronchoscopy under general anesthesia were subject to an atelectasis survey carried out by RP-EBUS under fluoroscopic guidance. The following dependent segments were evaluated: right bronchus 2 (RB2), RB6, RB9, and RB10; and left bronchus 2 (LB2), LB6, LB9, and LB10. Images were categorized either as aerated lung ("snowstorm" pattern) or as having a nonaerated/atelectatic pattern. Categorization was performed by three independent readers. RESULTS: Fifty-seven patients were enrolled. The overall intraclass correlation agreement among readers was 0.82 (95% CI, 0.71-0.89). Median time from anesthesia induction to atelectasis survey was 33 min (range, 3-94 min). Fifty-one patients (89%; 95% CI, 78%-96%) had atelectasis in at least one of the eight evaluated segments, 45 patients (79%) had atelectasis in at least three, 41 patients (72%) had atelectasis in at least four, 33 patients (58%) had atelectasis in at least five, and 18 patients (32%) had atelectasis in at least six segments. Right and left B6, B9, and B10 segments showed atelectasis in > 50% of patients. BMI and time to atelectasis survey were associated with increased odds of having more atelectatic segments (BMI: OR, 1.13 per unit change; 95% CI, 1.034-1.235; P = .007; time to survey: OR, 1.064 per minute; 95% CI, 1.025-1.105; P = .001). INTERPRETATION: The incidence of atelectasis developing during bronchoscopy under general anesthesia in dependent lung zones is high, and the number of atelectatic segments is greater with higher BMI and with longer time under anesthesia. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT03523689; URL: www.clinicaltrials.gov.

A 55-Year-Old Man With Cough and Hematochezia.

CASE PRESENTATION: A 55-year-old man presented to the ED with a 3-week history of worsening cough and shortness of breath. He had blood-tinged sputum, fever, night sweats, and a 2.7 kg weight loss within the same period. For the past few days, he had taken amoxicillin-clavulanate for presumed sinusitis. Despite this, his symptoms persisted, prompting him to seek further evaluation. His medical history was significant for ulcerative colitis and he had some bloody diarrhea for the past few weeks. Medications included aspirin, mesalamine, multivitamins, folic acid, and herbal supplements including gingko biloba, ginseng, and turmeric-ginger. He never smoked and drank alcohol occasionally. Family history was notable for stroke and myocardial infarction.

Bronchoscopic ablation of peripheral lung tumors.

Lung cancer is the leading cause of cancer-related death worldwide and lobectomy remains the standard of care for patients with early-stage non-small cell lung cancer (NSCLC). The combination of an aging population and the implementation of low-dose CT for lung cancer screening is leading to an increase in diagnosis of early stage NSCLC in medically "inoperable" patients. The recommended treatment for this latter group of patients is stereotactic body radiation therapy (SBRT). However, many patients cannot undergo SBRT because they have received prior radiation or because the tumor is located next to vital structures. Percutaneous ablative therapies have become an alternative to SBRT but, unfortunately, they all violate the pleura and are associated with high rate of pneumothorax. With a more favorable safety profile and the ability to provide also diagnosis and nodal staging, bronchoscopic ablation is hence emerging as a potential future therapeutic alternative for these patients. Herein we review the current state of the art including animal and human data that exists thus far. We also discuss technical and research challenges as well as future directions that this exciting new technology may take.

Lung Cancer.

Lung cancer is the world's leading cause of cancer death. Screening for lung cancer by low-dose computed tomography improves mortality. Various modalities exist for diagnosis and staging. Treatment is determined by subtype and stage of cancer; there are several personalized therapies that did not exist just a few years ago. Caring for the patient with lung cancer is a complex task. This review provides a broad outline of this disease, helping clinicians identify such patients and familiarizing them with lung cancer care options, so they are better equipped to guide their patients along this challenging journey.

Update on airway stents.

PURPOSE OF REVIEW: The current review describes the latest evidence regarding the use of stents for malignant airway obstruction. RECENT FINDINGS: Therapeutic bronchoscopy, including stenting, can restore patency in up to 93% of patients with malignant central airway obstruction. The patients that benefit the most are those with worse baseline dyspnea, higher American Society of Anesthesiology score, poorer functional status, and central obstruction (rather than lobar). Early complications are relatively rare with stent placement, whereas late complications are not. Stents are a risk factor for lower respiratory tract infection, which, in turn, is a negative prognostic factor in terms of survival. Recent research has seen the development of personalized stents via three-dimensional printing, mini stents for more distal airways, and stents with drug-eluting and biodegradable properties. SUMMARY: Airway stents must be judiciously used, but we now have data that help guide patient selection and that inform us of what potential complications may occur and when. Stents are under development with newer properties that may extend the therapeutic reach of these interventions.

Interactions between c-Jun, nuclear factor 1, and JC virus promoter sequences: implications for viral tropism.

The infectious cycle of the human polyomavirus JC (JCV) is ultimately regulated in cellular nuclei at the level of viral protein expression and genomic replication. Such activity is prompted by interactions between variant nucleotide sequences within the JCV regulatory region (promoter) and cellular transcription factors that bind specific DNA consensus sites. In previous work we identified an NF-1 class member, NF-1X, as a critical transcription factor affecting the JCV cellular host range. Within variant JCV promoters, as well as other viral and cellular promoters, adjacently located NF-1 and AP-1 consensus sites are often found. The close proximity of these two binding sites suggests the opportunity for interaction between NF-1 and AP-1 proteins. Here, by electrophoretic mobility shift assays, we show temporal and dose-dependent interference by an AP-1 family member, c-Jun, upon NF-1 proteins binding an NF-1 consensus site derived from JCV promoter sequence. Moreover, as demonstrated by protein-protein interaction assays, we identify specific binding affinity independent of DNA binding between NF-1X and c-Jun. Finally, to compare the binding profiles of NF-1X and c-Jun on JCV promoter sequence in parallel with in vivo detection of viral activity levels, we developed an anchored transcriptional promoter (ATP) assay. With use of extracts from JCV-infected cells transfected to overexpress either NF-1X or c-Jun, ATP assays showed concurrent increases in NF-1X binding and viral protein expression. Conversely, increased c-Jun binding accompanied decreases in both NF-1X binding and viral protein expression. Therefore, inhibition of NF-1X binding by c-Jun appears to play a role in regulating levels of JCV activity.

Traffic of JC virus from sites of initial infection to the brain: the path to progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disorder of the human brain caused by infection with the human polyomavirus, JC. Up to 80% of humans express serum antibodies to JC virus (JCV), yet considerably fewer people develop PML-predominantly those under immunosuppressive conditions. Recent research showed JCV infection in multiple tissues throughout the body, suggesting sites for viral latency. These observations allow the proposal of pathways that JCV may use from sites of initial infection to the brain. Results from investigations into cell-surface receptors, intracellular DNA-binding proteins, and variant viral regulatory regions also suggest mechanisms that may regulate cellular susceptibility to JCV infection. Together, these data elucidate how JCV may establish infection in various cell types, persist latently or become reactivated, and ultimately reach the brain to cause PML.