Advances in navigating to the nodule and targeting.

PURPOSE OF REVIEW: The multitude of available platforms and imaging modalities for navigational bronchoscopy, in combination with the various sampling tools that can be used intra-procedurally, is complex. This review seeks to describe the recent developments in peripheral bronchoscopy in regards to navigation, imaging, and sampling target lesions in the pulmonary parenchyma. RECENT FINDINGS: Robotic assisted bronchoscopy has improved navigation to the peripheral airways for sampling of peripheral parenchymal lesions. These navigational platforms use innovative technology utilizing electromagnetic navigation and shape-sensing technology for guidance. The greatest improvement has been the stabilization of the robotic scope in the periphery to allow for accurate sampling. Despite improvements in these platforms, limitations of CT to body divergence continue to impact navigation to the lesion and therefore diagnostic yield of the procedure. Advanced intraprocedural imaging with cone beam CT or augmented fluoroscopy has been a recent focus to improve this area. Further, the adoption of newer sampling tools, such as cryobiopsy, offers the possibility of increased diagnostic yield. SUMMARY: The developments in advanced bronchoscopy will impact the role of biopsy in the diagnosis of peripheral pulmonary parenchymal lesions.

Predicting malignant pleural effusion during diagnostic pleuroscopy with biopsy: A prospective multicentre study.

BACKGROUND AND OBJECTIVE: Pleuroscopy with pleural biopsy has a high sensitivity for malignant pleural effusion (MPE). Because MPEs tend to recur, concurrent diagnosis and treatment of MPE during pleuroscopy is desired. However, proceeding directly to treatment at the time of pleuroscopy requires confidence in the on-site diagnosis. The study's primary objective was to create a predictive model to estimate the probability of MPE during pleuroscopy. METHODS: A prospective observational multicentre cohort study of consecutive patients undergoing pleuroscopy was conducted. We used a logistic regression model to evaluate the probability of MPE with relation to visual assessment, rapid on-site evaluation (ROSE) of touch preparation and presence of pleural nodules/masses on computed tomography (CT). To assess the model's prediction accuracy, a bootstrapped training/testing approach was utilized to estimate the cross-validated area under the receiver operating characteristic curve. RESULTS: Of the 201 patients included in the study, 103 had MPE. Logistic regression showed that higher level of malignancy on visual assessment is associated with higher odds of MPE (OR = 34.68, 95% CI = 9.17-131.14, p < 0.001). The logistic regression also showed that higher level of malignancy on ROSE of touch preparation is associated with higher odds of MPE (OR = 11.63, 95% CI = 3.85-35.16, p < 0.001). Presence of pleural nodules/masses on CT is associated with higher odds of MPE (OR = 6.61, 95% CI = 1.97-22.1, p = 0.002). A multivariable logistic regression model of final pathologic status with relation to visual assessment, ROSE of touch preparation and presence of pleural nodules/masses on CT had a cross-validated AUC of 0.94 (95% CI = 0.91-0.97). CONCLUSION: A prediction model using visual assessment, ROSE of touch preparation and CT scan findings demonstrated excellent predictive accuracy for MPE. Further validation studies are needed to confirm our findings.

Equipment and procedural setup for interventional pulmonology procedures in the intensive care unit.

Procedural setup is an important aspect of any procedure. Interventional pulmonologists provide a procedural practice and have additional expertise in performing high-risk procedures needed in the critically ill patients in intensive care. Taking the time to plan the procedure setup in advance and having all necessary equipment readily available at the patient's bedside is imperative for procedural services. This is especially essential to ensure patient safety, minimize risk of complications, and improve success for specialized procedures performed by interventional pulmonary in the intensive care unit. In this review we describe the equipment and procedural setup ideal for both pleural and airway procedures. These include flexible diagnostic and therapeutic bronchoscopy, ultrasound guided thoracentesis, chest tube insertion, difficult airway management, and bedside percutaneous dilatation tracheostomy. We provide a guide checklist for these procedures emphasizing the practical aspects of each procedure from selecting the appropriate size endotracheal tube to operator positioning to ensure efficiency and best access. The components of procedural setup are discussed in relation to patient factors that include patient positioning and anesthesia, personnel in the procedure team and the equipment itself. We further briefly describe the additional equipment needed for specialized techniques in therapeutic bronchoscopy used by interventional pulmonologists.

Sulfa-induced acute eosinophilic pneumonia.

Acute eosinophilic pneumonia (AEP) is an infrequently seen interstitial lung disease secondary to medications. We report a series of 3 case of severe AEP which developed as a result of sulfa medication. 2 patients had received treatment with sulfamethoxazole for acne and 1 was treated with sulfasalazine for colitis. Patients were on sulfa medication for 1-3 weeks prior to presentation. All patients presented with fever, acute onset bilateral pulmonary infiltrates as well as marked peripheral eosinophilia. Mean eosinophil count was 2.21 × 109/L. There was a lack of response to steroids. One patient required extracorporeal membrane oxygenation and prolonged mechanical ventilation via tracheostomy. 2 patients underwent successful lung transplantation (1 bilateral living-related lobar lung transplant and 1 orthotropic cardiopulmonary allotransplantation). In all cases lung biopsy and explants showed acute and organizing diffuse alveolar damage with increased interstitial and airspace eosinophils. To our knowledge, our series is the first to show the clinical features of sulfa induced AEP in an adolescent population.

Lung cancer in combined pulmonary fibrosis and emphysema: a large retrospective cohort analysis.

BACKGROUND: Combined pulmonary fibrosis and emphysema (CPFE) is characterised by upper lobe emphysema and lower lobe fibrosis. Our study aim was to determine the incident risk, presenting characteristics and outcome of lung cancer diagnoses in a cohort of CPFE patients over time. MATERIALS AND METHODS: We conducted a retrospective cohort study assessing patients with radiological CPFE followed over a median of 76 months (range 1-237 months). Interval development of lung cancer and clinicopathological characteristics of those with and without lung cancer were compared and survival analysis performed. RESULTS: Lung cancer occurred in 26 (11.6%) out of 230 CPFE patients, dominated by nonsmall cell lung cancer (88%, n=23) with squamous cell carcinoma comprising the majority (57%, n=13). There was a predominance of lower lobe (62%) and subpleural (64%) radiological presentation. Survival was reduced for the whole cohort by lung cancer even after adjusting for a priori covariables of age, sex, smoking pack-years, presenting forced vital capacity and radiological honeycombing. Univariable predictors of increased mortality after lung cancer diagnosis included honeycombing (hazard ratio (HR) 3.03, 95% CI 1.16-7.91; p=0.02) and later stage presentation (HR 4.77, 95% CI 1.8-14.94; p=0.001), with those able to undergo surgical resection having better survival (HR 0.29, 95% CI 0.09-0.87; p=0.02). CONCLUSION: Lung cancer occurred in 26 (11.6%) out of 230 CPFE patients and was dominated by squamous cell carcinoma presenting in a lower lobe peripheral distribution. Surgical resection appeared to improve survival in selected patients with earlier stage disease. Further studies are needed to develop a relevant screening programme for CPFE patients.

Endobronchial ultrasound- guided transbronchial needle aspiration for mediastinal lymph node staging in patients with typical pulmonary carcinoids.

BACKGROUND: Pulmonary carcinoids, which are well-differentiated lung neuroendocrine carcinomas, account for only 1-2 % of primary lung malignancies. Although fluorodeoxyglucose positron-emission tomography/computed tomography performs poorly in the identification of mediastinal lymph node metastases, particularly for pulmonary carcinoids, endobronchial ultrasound-guided (EBUS) transbronchial needle aspiration (TBNA) may be a useful means of preoperative nodal assessment in patients with these conditions. However, the diagnostic performance of EBUS TBNA is unknown. This study was designed to determine the sensitivity of EBUS for mediastinal staging in patients with typical carcinoid. STUDY DESIGN AND METHODS: A retrospective review of all patients with carcinoids who underwent EBUS TBNA and/or surgical resection with lymphadenectomy at The University of Texas MD Anderson Cancer Center was performed. The sensitivity of EBUS -TBNA in diagnosis of mediastinal lymph node metastases was determined. RESULTS: Of the 212 patients with pulmonary carcinoids we identified, 137 had surgery with no preoperative EBUS TBNA, 68 had EBUS TBNA followed by surgery, and 7 had EBUS TBNA only. The sensitivity rate for EBUS TBNA in diagnosis of mediastinal lymph node metastases was 77.78 % overall (95 % CI, 57.7-91.3%) and it was 87.5 % (95 % CI, 67.6-97.3%) when we considered only patients with EBUS TBNA-accessible lymph nodes. DISCUSSION: The sensitivity of EBUS TBNA for diagnosis of mediastinal lymph node metastases of pulmonary carcinoids was slightly lower than that reported previously for non-small cell lung cancer. Preoperative EBUS TBNA identified nodal metastases not previously identified by imaging.

Management of the solitary pulmonary nodule.

PURPOSE OF REVIEW: We review the categorization and management of solitary pulmonary nodules. RECENT FINDINGS: The National Comprehensive Cancer Network guidelines were updated in 2018 and the revised Fleischner Society guidelines were published in 2017. The revised Fleischner Society guidelines published in 2017 have less frequent follow-up recommendations for incidentally detected pulmonary nodules with longer intervals between subsequent CT scans. The updated 2018 version of National Comprehensive Cancer Network lung cancer screening guidelines provide recommendations for screen-detected nodules based on a patient's risk of cancer. New molecular assays may be of use in patients with a pretest probability of malignancy less than 50%. When these tests indicate low risk, a strategy of follow-up CT imaging may be feasible, avoiding unnecessary invasive testing. However, further clinical utility studies are needed in this area. SUMMARY: Management options for pulmonary nodules include watchful waiting with follow-up CT imaging, PET imaging, or further invasive testing based on probability of malignancy. With a low estimated risk of malignancy in an incidentally detected solitary pulmonary nodule, longer intervals between follow-up CT scans are recommended for patients. For patients at high risk for malignancy or those with nodules of at least 8 mm, either incidentally, screen detected, or symptom driven, a diagnostic biopsy is necessary to establish the cause of a solitary pulmonary nodule.

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.

Combined pulmonary fibrosis and emphysema as a clinicoradiologic entity: Characterization of presenting lung fibrosis and implications for survival.

BACKGROUND: The prevalence of classifiable and unclassifiable causes of lung fibrosis and its implications for survival are mostly unknown in combined pulmonary fibrosis and emphysema (CPFE). MATERIALS AND METHODS: Patients with >10% involvement of both emphysema and lung fibrosis seen over 11 years at our institution were reviewed independently by expert radiologists for fibrotic and emphysematous findings and overall fibrotic CT pattern. Underlying interstitial lung disease (ILD) diagnoses and baseline demographic and clinical characteristics were collated and assessed for predictors of comparative survival. RESULTS: In this retrospective cohort, 179 CPFE patients were identified and categorized as 58 usual interstitial pneumonia/idiopathic pulmonary fibrosis (UIP/IPF) (32%), 42 secondary ILD (23%), and 79 unclassifiable ILD (44%). The most prevalent (47%) radiologic pattern was 'unclassifiable', followed by 'consistent' and 'possible' UIP pattern in 38%. Adjusted predictors of mortality for the cohort as a whole included age (HR 1.03[1.01-1.06], P = 0.002), percent predicted diffusing capacity for carbon monoxide (unit HR 0.97 [0.96-0.99], P = 0.001), honeycombing (HR 1.58 [1.02-2.43], P = 0.04), and right ventricular dysfunction (HR 2.28 [1.39-3.97], P = 0.002). Survival was similar between CPFE with secondary ILD and CPFE with UIP/IPF, while CPFE with unclassifiable ILD had better comparative survival (Log rank = 0.026). CONCLUSIONS: Our findings suggest only about a third of CPFE patients represent suspected UIP/IPF; the majority were clinically and radiologically unclassifiable ILD whose survival was comparatively better. Identifiable or secondary causes of lung fibrosis in CPFE occurred in about a fifth of presenting patients.

Bronchial thermoplasty-an update.

Bronchial Thermoplasty is a procedure that involves the delivery of radiofrequency energy during bronchoscopy to airways in order to selectively ablate airway smooth muscles. Bronchial Thermoplasty was approved by the FDA in 2010 and remains the only device based non-pharmacological treatment approach for severe asthma. We appraise the trials leading to the approval of Bronchial Thermoplasty in light of the FDA approval process. Current international guidelines regarding use of Bronchial Thermoplasty and emering pharmacological options for severe asthma are reviewed.

Trends in Use of Midodrine in the ICU: A Single-Center Retrospective Case Series.

OBJECTIVES: Midodrine is an oral alpha-agonist approved for orthostatic hypotension. The use of midodrine as a vasopressor sparing agent has steadily increased in the ICU despite limited evidence for its safety in that setting. We describe the trends in use and reported side effects and complications of midodrine in multidisciplinary ICUs of a tertiary care institution. DESIGN: Single-center retrospective case series. SETTING: Medical and surgical ICU patients from January 2011 to October 2016 at Mayo Clinic, Rochester. PATIENTS: Adult patients admitted to any ICU who received midodrine for hypotension were eligible. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We reviewed the mean arterial pressures and cumulative vasopressor dose before and after midodrine administration and assessed for reported complications. During the study period, a total of 1,119 patients were initiated on midodrine, 56% in surgical ICUs, 42% in medical ICUs, and 2% in a mixed medical and surgical neurology ICU. There was a significant decrease in the number of patients on vasopressors 24 hours after initiation of midodrine (663 to 344; p < 0.001); among the patients that remained on vasopressors, there was a significant decrease in the median cumulative vasopressor dose (p = 0.002). There was a significant increase in median mean arterial pressure 24 hours after initiation of midodrine among patients who were not on vasopressors (65-68; p < 0.01). Asymptomatic bradycardia (heart rate < 50 beats/min) was the most common side effect (n = 172 patients, median 39 beats/min). Two patients developed bowel ischemia after initiation of midodrine that prompted discontinuation of midodrine in one case. Evaluating trends of utilization, the off-label use of midodrine has increased steadily over the years across ICUs. CONCLUSIONS: Our results suggest that midodrine is being increasingly used as an adjunct to increase mean arterial pressure and facilitate weaning of vasopressors in the ICU. Prospective trials are required to further establish the appropriate timing, efficacy, safety, and cost-effectiveness of midodrine use in ICU patients.

Practical Implementation of Failure Mode and Effects Analysis for Extracorporeal Membrane Oxygenation Activation.

Extracorporeal membrane oxygenation (ECMO) is used to treat severe hypoxemic respiratory failure and as a rescue therapy for patients with cardiopulmonary arrest within a narrow window of time. A failure modes and effects analysis (FMEA) was conducted to analyze the clinical and operational processes leading to delays in initiating ECMO. FMEA determined these highest-risk failure modes that were contributing to process failure: (1) ECMO candidacy not determined in time, (2) no or incomplete evaluation for ECMO prior to consult or arrest, (3) ECMO team not immediately available, and (4) cannulation not completed in time. When implemented collectively, a total of 4 interventions addressed more than 95% of the system failures. These interventions were (1) ECMO response pager held by a team required for decision, (2) distribution of institutionally defined inclusion/exclusion criteria, (3) educational training for clinicians consulting the ECMO team, and (4) establishment of a mobile ECMO insertion cart.

Methylene Blue for Bronchopleural Fistula Localization.

A bronchopleural fistula (BPF) is a communication between the pleural space and the bronchial tree. BPFs are challenging to diagnose and are associated with a high morbidity and mortality. Sequential balloon occlusion is commonly used for localization of a BPF. We describe our experience with 4 cases of successful localization of the BPF by instillation of methylene blue into the pleural space through a pigtail catheter, with simultaneous bronchoscopic visualization of dye in the tracheobronchial tree. Two patients were treated with endobronchial valves and 3 had a surgical thoracic muscle flap placed.

A deep-sea diver with cement pulmonary embolism.

Cement pulmonary embolism is a rare complication of cement kyphoplasty. These emboli are often asymptomatic and commonly detected many years after the procedure as incidental findings on radiographic imaging. We herein report a case of a 32-year-old professional diver who was diagnosed with asymptomatic cement pulmonary emboli during his annual diving physical exam. After two years of follow-up the patient remained asymptomatic and resumed his career in professional diving, which included deep sea diving activities with no evidence of respiratory limitations or long-term complications.

Tunneled pleural catheter dysfunction: case report and review of complications.

Tunneled pleural catheters (TPC) are often used for management of malignant pleural effusion. They have proven to be safe, effective, and are associated with low rates of complications. We describe the case of a patient with metastatic renal cell carcinoma who inadvertently cut his TPC causing leakage of pleural fluid, requiring urgent removal. We review the reported complications of TPC in the literature and suggest close vigilance of patients at risk to have altered mental status who undergo placement of TPC.

Antimicrobial Photodynamic Therapy with Functionalized Fullerenes: Quantitative Structure-activity Relationships.

Photosensitive dyes or photo sensitizers (PS) in combination with visible light and oxygen produce reactive oxygen species that kill cells in the process known as photodynamic therapy (PDT). Antimicrobial PDT employs PS that is selective for microbial cells and is a new treatment for infections. Most antimicrobial PS is based on tetrapyrrole or phenothiazinium structures that have been synthesized to carry quaternary cationic charges or basic amino groups. However we recently showed that cationic-substituted fullerene derivative were highly effective in killing a broad spectrum of microbial cells after illumination with white light. In the present report we compared a new group of synthetic fullerene derivatives that possessed either basic or quaternary amino groups as antimicrobial PS against Gram-positive (Staphylococcus aureus), Gram-negative bacteria (Escherichia coli) and fungi (Candida albicans). Quantitative structure-function relationships were derived with LogP and hydrophilic lipophilic balance parameters. Compounds with non-quaternary amino groups tended to form nanoaggregates in water and were only effective against S. aureus. The most important determinant of effectiveness was an increased number of quaternary cationic groups that were widely dispersed around the fullerene cage to minimize aggregation. S. aureus was most susceptible; E. coli was intermediate, while C. albicans was the most resistant species tested. The high effectiveness of antimicrobial PDT with quaternized fullerenes suggest they may have applications in treatment of superficial infections (for instance in wounds and burns) where light penetration into tissue is not problematic.

Use of tranexamic acid is a cost effective method in preventing blood loss during and after total knee replacement.

BACKGROUND & PURPOSE: Allogenic blood transfusion in elective orthopaedic surgery is best avoided owing to its associated risks. Total knee replacement often requires blood transfusion, more so when bilateral surgery is performed. Many strategies are currently being employed to reduce the amount of peri-operative allogenic transfusions. Anti-fibrinolytic compounds such as aminocaproic acid and tranexamic acid have been used systemically in perioperative settings with promising results. This study aimed to evaluate the effectiveness of tranexamic acid in reducing allogenic blood transfusion in total knee replacement surgery. METHODOLOGY: This was a retrospective cohort study conducted on patients undergoing total knee replacement during the time period November 2005 to November 2008. Study population was 99 patients, of which 70 underwent unilateral and 29 bilateral knee replacement. Forty-seven patients with 62 (49.5%) knees (group-I) had received tranexamic acid (by surgeon preference) while the remaining fifty-two patients with 66 (51.5%) knees (group-II) had did not received any tranexamic acid either pre- or post-operatively. RESULTS: The mean drop in the post-operative haemoglobin concentration in Group-II for unilateral and bilateral cases was 1.79 gm/dl and 2.21 gm/dl, with a mean post-operative drainage of 1828 ml (unilateral) and 2695 ml (bilateral). In comparison, the mean drop in the post-op haemoglobin in Group-I was 1.49 gm/dl (unilateral) and 1.94 gm/dl (bilateral), with a mean drainage of 826 ml (unilateral) and 1288 ml (bilateral) (p-value < 0.001). INTERPRETATION: Tranexamic acid is effective in reducing post-operative drainage and requirement of blood transfusion after knee replacement.

Diffuse large B cell lymphoma (DLBCL) in Pakistan: an emerging epidemic?

There has been a recent concern among oncological clinicians and pathologists of our region regarding the disproportionate increase in the number of patients presenting with diffuse large B cell lymphoma (DLBCL). This prompted us to conduct a thorough, hospital-based epidemiological study in a major referral center of Pakistan. A total of 780 specimens were collected over last half decade from cases classified as adult Non Hodgkin's lymphoma (NHL). Out of these 780, 596 (76.4 %) were diagnosed as DLBCLs. The gender ratio was 2.3:1 (M:F) and the median age was 47.2 years, with an age range of 15-85 years. Nodal-NHLs constituted 42.2 % of all adult NHLs, with the cervical lymph nodes as the most frequent nodal site of presentation. The most frequent extranodal site was the gastro-intestinal tract (GIT), followed by the head and neck. In conclusion, we document an astonishingly high number of DLBCL amounting to an emerging epidemic in Pakistan, with a consideration of probable etiopathogenetic factors.