Referral rates and barriers to lung transplantation based on pulmonary function criteria in interstitial lung diseases: a retrospective cohort study.

BACKGROUND: Interstitial lung diseases (ILD) unresponsive to medical therapy often require lung transplantation (LTx), which prolongs quality of life and survival. Ideal timing for referral for LTx remains challenging, with late referral associated with significant morbidity and mortality. Among other criteria, patients with ILD should be considered for LTx if forced vital capacity (FVC) is less than 80% or diffusion capacity for carbon monoxide (DLCO) is less than 40%. However, data on referral rates are lacking. OBJECTIVES: To evaluate referral rates for LTx based on pulmonary function tests (PFTs) and identify barriers associated with non-referral. DESIGN: A single-center retrospective cohort study. METHODS: The study consisted of ILD patients who performed PFT between 2014 and 2020. Patients with FVC < 80% or a DLCO < 40% were included in the study. Patients with absolute contraindications to LTx were excluded. Referral rates were computed, and a comparison was made between referred and non-referred subjects. RESULTS: Out of 114 ILD patients meeting criteria for referral to LTx, 35 were referred (30.7%), and 7 proceeded to undergo LTx. Median time from PFT to referral for assessment was 255 days [interquartile range (IQR) 35-1077]. Median time from referral to LTx was 89 days (IQR 59-143). Referred patients were younger (p = 0.003), had lower FVC (p < 0.001), DLCO (p < 0.001), and a higher rate of pulmonary hypertension (p = 0.04). Relatively better PFT, and older age, were significantly associated with non-referral of patients. CONCLUSION: There is under-referral of ILD patients who are eligible for LTx, which is associated with severe disease and missed opportunities for LTx. Further research is required to validate these findings.

Lung transplants: addressing referral gaps for lung disease patientsPatients with severe lung diseases that are unresponsive to medical treatments often require lung transplants to enhance their quality of life and survival. Determining the optimal timing for considering a transplant is challenging, as delaying it can lead to complications. Our study aimed to assess how frequently individuals with lung problems, particularly interstitial lung diseases, were referred for lung transplants based on lung function tests. We conducted a retrospective analysis of medical records for patients with lung diseases who underwent lung function tests between 2014 and 2020. We selected patients whose test results indicated impaired lung function, excluding those who were ineligible for lung transplants due to other medical reasons. Subsequently, we examined the number of patients referred for a lung transplant and compared them to those who were not referred. Our findings revealed that out of 114 patients eligible for a lung transplant, only 35 were referred, representing a referral rate of approximately 31%. Among these, only 7 patients actually underwent the transplant procedure. The time elapsed between the lung function test and the referral for a transplant assessment was notably long, averaging around 255 days. Additionally, once referred, patients waited an average of 89 days for the transplant assessment. Referred patients tended to be younger and had more severe lung disease, characterized by lower lung function test results and a higher likelihood of pulmonary hypertension. Conversely, patients who were not referred generally enjoyed better overall health and were older. This discrepancy highlights the missed opportunities for patients to improve their health and quality of life through lung transplantation. Further research is essential to verify the accuracy of these findings, but this study represents a crucial step toward ensuring that individuals with lung diseases receive the appropriate care they require.

Persistent Severe Acute Respiratory Syndrome Coronavirus 2 Pneumonia in Patients Treated With Anti-CD20 Monoclonal Antibodies.

We report 8 cases of persistent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia in patients previously treated with anti-CD20 monoclonal antibodies. Polymerase chain reaction of nasopharyngeal swabs for SARS-CoV-2 was negative in most cases; viral cell cultures confirmed that viable SARS-Co-2 virus was present. Four patients were treated with anti-SARS-CoV-2 hyperimmune globulins with rapid resolution of disease.

Timing of Lung Transplant Referral in Patients with Severe COVID-19 Lung Injury Supported by ECMO.

Severe respiratory failure caused by COVID-19 often requires mechanical ventilation, including extracorporeal membrane oxygenation (ECMO). In rare cases, lung transplantation (LTx) may be considered as a last resort. However, uncertainties remain about patient selection and optimal timing for referral and listing. This retrospective study analyzed patients with severe COVID-19 who were supported by veno-venous ECMO and listed for LTx between July 2020 and June 2022. Out of the 20 patients in the study population, four who underwent LTx were excluded. The clinical characteristics of the remaining 16 patients were compared, including nine who recovered and seven who died while awaiting LTx. The median duration from hospitalization to listing was 85.5 days, and the median duration on the waitlist was 25.5 days. Younger age was significantly associated with a higher likelihood of recovery without LTx after a median of 59 days on ECMO, compared to those who died at a median of 99 days. In patients with severe COVID-19-induced lung damage supported by ECMO, referral to LTx should be delayed for 8-10 weeks after ECMO initiation, particularly for younger patients who have a higher probability of spontaneous recovery and may not require LTx.

Virtual reality utilization for left atrial appendage occluder device size prediction.

Aim: To explore the feasibility and accuracy of virtual reality (VR) derived from cardiac computed angiography (CCTA) data to predict left atrial appendage occlusion (LAAO) device size. Method: Retrospective data of patients who underwent LAAO according to clinical indication were reviewed; all patients underwent a pre-procedural CCTA. Measurements of the left atrial appendage (LAA) orifice diameters by CCTA, VR, and transesophageal echocardiography (TEE) (acquired during the procedure) were compared to the implanted device size. The LAA perimeter was calculated using the Ramanujan approximation. Statistical analyses included Lin's Concordance Correlation Coefficient (ρ c ), the mean difference, and the mean square error (MSE). Results: The sample was composed of 20 patients (mean age 75.7 ± 7.5 years, 60% males) who underwent successful LAAO insertion (ACP™ N = 8, Watchman™ N = 12). The CCTA, VR, and TEE maximal diameter ρ c was 0.52, 0.78 and 0.60, respectively with mean differences of +0.92 ± 4.0 mm, -1.12 ± 2.3 mm, and -3.45 ± 2.69 mm, respectively. The CCTA, VR, and TEE perimeter calculations ρ c were 0.49, 0.54, and 0.39 respectively with mean differences of +4.69 ± 11.5 mm, -9.88 ± 8.0 mm, and -16.79 ± 7.8 respectively. Discussion: A VR visualization of the LAA ostium in different perspectives allows for a better understanding of its funnel-shaped structure. VR measurement of the maximal ostium diameter had the strongest correlation with the diameter of the inserted device. VR may thus provide new imaging possibilities for the evaluation of complex pre-procedural structures such as the LAA.

Proof of concept: Comparative accuracy of semiautomated VR modeling for volumetric analysis of the heart ventricles.

Introduction: Simpson's rule is generally used to estimate cardiac volumes. By contrast, modern methods such as Virtual Reality (VR) utilize mesh modeling to present the object's surface spatial structure, thus enabling intricate volumetric calculations. In this study, two types of semiautomated VR models for cardiac volumetric analysis were compared to the standard Philips dedicated cardiac imaging platform (PDP) which is based on Simpson's rule calculations. Methods: This retrospective report examined the cardiac computed tomography angiography (CCTA) of twenty patients with atrial fibrillation obtained prior to a left atrial appendage occlusion procedure. We employed two VR models to evaluate each CCTA and compared them to the PDP: a VR model with Philips-similar segmentations (VR-PS) that included the trabeculae and the papillary muscles within the luminal volume, and a VR model that only included the inner blood pool (VR-IBP). Results: Comparison of the VR-PS and the PDP left ventricle (LV) volumes demonstrated excellent correlation with a ρ c of 0.983 (95% CI 0.96, 0.99), and a small mean difference and range. The calculated volumes of the right ventricle (RV) had a somewhat lower correlation of 0.89 (95% CI 0.781, 0.95), a small mean difference, and a broader range. The VR-IBP chamber size estimations were significantly smaller than the estimates based on the PDP. Discussion: Simpson's rule and polygon summation algorithms produce similar results in normal morphological LVs. However, this correlation failed to emerge when applied to RVs and irregular chambers. Conclusions: The findings suggest that the polygon summation method is preferable for RV and irregular LV volume and function calculations.

Comparison of Speckle Tracking Echocardiography During Different Pacing Modalities for Cardiac Resynchronization Therapy Response Prediction.

Background: The aim of this study was to evaluate left ventricular mechanical activation pattern by speckle tracking echocardiography (STE) as a predictor of response to cardiac resynchronization therapy (CRT) in patients with heart failure. Methods: Echocardiography was performed during no pacing, right ventricular pacing (RVP), biventricular pacing (BVP) and multipolar pacing (MPP) immediately after CRT implantation in 16 patients at a single centre. Seven patients were diagnosed as responders and 9 patients as non-responders after 6 months of standard CRT pacing. All had adequate short axis views, and 1 CRT responder and 2 CRT non-responders had limited longitudinal views. Results: Longitudinal and circumferential global strain (GS) and global strain rate (GSR) or their change analysis, did not yield any CRT response prediction. However, the longitudinal BVP/RVP GS ratio was significantly higher in the responder group (1.32 ± 0.2%, 2.0 ± 0.4% and 1.9 ± 0.4%), compared with the non-responder group (1.06 ± 0.2%, 1.1 ± 0.4% and 1.2 ± 0.4%) in the apical two-chamber, APLAX and four-chamber views, respectively. Similarly, the longitudinal BVP/RVP GSR at active systolic phase (GSRs) was significantly higher in the responder group (1.9 ± 0.9% and 1.7 ± 0.4%) compared with the non-responder group (1.0 ± 0.4% and 1.1 ± 0.2%) in the apical APLAX and four-chamber views, respectively. Measurements of the strain delay index showed predictive power regarding CRT response in non-paced patients. Conclusion: Post implantation, longitudinal BVP/RVP GS and GSRs ratios of 1.4% and above may be useful as a CRT response prediction tool. Furthermore, our findings support the usefulness of strain delay index prior to CRT implantation in non-paced patients.

Soluble HLA peptidome of pleural effusions is a valuable source for tumor antigens.

BACKGROUND: Soluble human leucocyte antigen (sHLA) molecules, released into the plasma, carry their original peptide cargo and provide insight into the protein synthesis and degradation schemes of their source cells and tissues. Other body fluids, such as pleural effusions, may also contain sHLA-peptide complexes, and can potentially serve as a source of tumor antigens since these fluids are drained from the tumor microenvironment. We explored this possibility by developing a methodology for purifying and analyzing large pleural effusion sHLA class I peptidomes of patients with malignancies or benign diseases. METHODS: Cleared pleural fluids, cell pellets present in the pleural effusions, and the primary tumor cells cultured from cancer patients' effusions, were used for immunoaffinity purification of the HLA molecules. The recovered HLA peptides were analyzed by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) and the resulting LC-MS/MS data were analyzed with the MaxQuant software tool. Selected tumor antigen peptides were tested for their immunogenicity potential with donor peripheral blood mononuclear cells (PBMCs) in an in vitro assay. RESULTS: Mass spectrometry analysis of the pleural effusions revealed 39,669 peptides attributable to 11,305 source proteins. The majority of peptides identified from the pleural effusions were defined as HLA ligands that fit the patients' HLA consensus sequence motifs. The membranal and soluble HLA peptidomes of each individual patient correlated to each other. Additionally, soluble HLA peptidomes from the same patient, obtained at different visits to the clinic, were highly similar. Compared with benign effusions, the soluble HLA peptidomes of malignant pleural effusions were larger and included HLA peptides derived from known tumor-associated antigens, including cancer/testis antigens, lung-related proteins, and vascular endothelial growth factor pathway proteins. Selected tumor-associated antigens that were identified by the immunopeptidomics were able to successfully prime CD8+ T cells. CONCLUSIONS: Pleural effusions contain sHLA-peptide complexes, and the pleural effusion HLA peptidome of patients with malignant tumors can serve as a rich source of biomarkers for tumor diagnosis and potential candidates for personalized immunotherapy.

Physiological Effects of Wearing N95 Respirator on Medical Staff During Prolong Work Hours in Covid-19 Departments.

OBJECTIVE: The objective of the current study was to determine gas exchange abnormalities and physiological changes among healthcare workers during a 4-hour emergency department (ED) shift while wearing the N95 respirator. METHODS: Single-center prospective observational study. Comparisons of paired measurements were performed using a non-parametric Wilcoxon matched-pairs signed-rank test. Results: Forty-one subjects were included. Prolonged N95 respirator use was associated with a significant decline in plasma pH (7.35 mmHg vs 7.34 mmHg, P = 0.02), PvO 2 (23.2 mmHg vs 18.6 mmHg, P < 0.001) and a concurrent increase in EtCO 2 (32.5 mmHg vs 38.5 mmHg, P < 0.0001). PvCO 2 and bicarbonate levels did not differ. No significant change was observed for heart rate or oxygen saturation. CONCLUSION: Using an N95 respirator for prolonged periods by healthcare professionals may provoke changes in gas exchange. The clinical significance of these changes remains to be determined.

A Review of Symptoms and Complications of Ultrasound Assisted Thoracentesis in the First Specialist Pleural Clinic in Israel.

BACKGROUND: Our 1600-bed teaching hospital opened the first physician-led specialist pleural service in Israel in November 2016. Thoracentesis is one of the frequently performed procedures in clinic. OBJECTIVES: To review the incidence of thoracentesis-related symptoms, complications, and risk factors in a specialist pleural clinic. METHODS: Prospective analysis was conducted of 658 ultrasound-assisted thoracenteses between November 2016 and November 2019. Data were collected on patient demographics, clinical characteristics, procedural aspects, symptoms, complications, and additional interventions required. RESULTS: Of the procedures, 24% were accompanied by a reported symptom of any intensity or duration. Cough and chest discomfort were noted in 56.4% and 52% of these cases, respectively. Large-volume drainage was associated with symptoms (P = 0.002). Ultrasound-estimated effusion volume before drainage predicted pain (P = 0.001) and pneumothorax (P = 0.021). Of 8 cases of pneumothorax, 6 were due to non-expandable lung. Two patients were hospitalized (0.3%), and one required a chest drain. CONCLUSIONS: Symptoms are a common feature of thoracentesis even when performed by experienced operators in ideal settings. Complications, however, are rare when the procedure is performed with bedside ultrasound and attention is paid to patient-reported symptoms and volume drained. Specialist pleural clinics provide a good model for a standardized approach to safe performance of this common procedure.

Early Blood-based Liquid Biopsy in Patients with Treatment-naïve Metastatic Adenocarcinoma of the Lung: A Case Series.

BACKGROUND: Guidelines recommend testing for multiple biomarkers in non-small cell lung cancer (NSCLC) tumors. Blood-based liquid biopsy analyzing cell-free DNA (cfDNA) could be used in addition to tumor biopsy genotyping, especially if tissue/time are limiting. OBJECTIVES: To investigate the clinical utility of early cfDNA analysis (Guardant360® CDx) in treatment-naïve NSCLC patients. METHODS: A prospective cohort of treatment-naïve patients with metastatic NSCLC who underwent tumor and cfDNA analysis between 12/2018 and 2/2019 were included. RESULTS: Ten patients were included: 6 males, median age 70.5 years (range 48-87), 8 prior smokers. Liquid biopsy was sent when cancer cells were detected in the biopsy specimen. Median time from diagnosis to receiving the report on the last biomarker from the tumor biopsy was 20 days (range 9-34); median time from blood draw to receiving the cfDNA findings was 9 days (range 7-12). The median difference between the cfDNA and the tumor analysis reports was 20 days (range 9-28). Actionable biomarkers were identified in four patients by both the biopsy analysis and the cfDNA analysis (2cases with EGFR mutations, one with ROS1 fusion, and one with EML4-ALK fusion for whom the biopsy analysis also identified an EGFR mutation not detected in the cfDNA analysis). Overall, eight patients received treatment (2 died before treatment initiation). Three patients received biomarker-based treatment (1 osimertinib, 1 alectinib, and 1 crizotinib). CONCLUSIONS: These findings suggest that cfDNA analysis should be ordered by the pulmonologists early in the evaluation of patients with NSCLC, which might complement the tumor biopsy.

Image-guidance triggered adaptive replanning of radiation therapy for locally advanced lung cancer: an evaluation of cases requiring plan adaptation.

OBJECTIVES: Anatomic changes may occur during chemoradiation treatment for lung cancers, requiring adaptive replanning. Here we characterize these cases. METHODS: We retrospectively studied lung cancer cases that underwent resimulation and adaptive replanning during 1/2016-3/2019. We compared first and second CT-simulation regarding tumor location, timing of change, tumor volume, anatomical alteration and change in simulation technique. We also compared dosimetric parameters between the plans, recorded local control, and overall survival outcomes. RESULTS: Out of 281 patients, 58 underwent replanning (20.6%). Histology included small cell (22.4%) and non-small cell (77.6%). Stage III was in 91.4%. Mean radiation dose of 59.4 Gray (Gy) (range 50-66Gy).Tumor location was peribronchial in 53.5%. Timing of replanning was in the first, second and final third of the treatment course in 26%, 43% and 31% respectively. Changes in gross tumor volume were observed in 74%; mean gross tumor volume was 276.7cc vs 192.7 cc (first vs second simulation, p = 0.001). Anatomical changes were identified in 35.4% including pleural fluid accumulation, atelectasis or pneumothorax alteration. Change in simulation technique was performed in 25.9%, including breath-hold or continuous positive airway pressure.Changes in dosimetric parameters when the same technique was used: lung V20Gy 26% (standard deviation, SD 7.6) vs 25.3% (SD 6.6) (p = 0.36), mean lung dose 15.1 Gy (SD 3.7) vs 14.7Gy (SD 3.3) (p = 0.23), heart V40Gy 10.2% (SD13) vs 7.2% (SD 9.8) (p = 0.037). When simulation technique changed: lung V20Gy 30.8% (SD 8.2) vs 27.3% (SD 8) (p = 0.012), mean lung dose 17.3 Gy (SD 4.4) vs 15.3 Gy (SD 3.8) (p = 0.007), heart V40Gy 11.1% (SD 14.7) vs 6.5% (SD 6.7) (p = 0.014).2 year local control was 60.7% (95% confidence interval, 34.5-79.2%), and median overall survival was 19.7 months. CONCLUSION: Adaptive replanning of radiation was performed in a fifth of locally advanced lung cancer patients. In most cases tumor volume decreased, or atelectasis resolved, causing mediastinal shifts, which, if unidentified and left uncorrected, may have led to local failure and increased toxicity. The heart V40Gy was reduced significantly in all cases, but significant reduction in lung doses was evident only if simulation technique was altered. ADVANCES IN KNOWLEDGE: In locally advanced lung cancer image-guidance with cone beam CT can detect significant mediastinal shifts and gross tumor volume changes that raise the need for adaptive replanning. Image guidance-triggered adaptive replanning should be added to the armament of advanced radiation treatment planning in locally advanced lung cancer.

Flexible bronchoscopy and cryoextraction for critical airway obstruction caused by an endobronchial angioleiomyoma.

Angioleiomyomas are rare airway tumours with potential to cause central airway obstruction or haemoptysis. Methods described to manage them include surgical resection, or rigid bronchoscopy and thermal ablation techniques. We describe a case presenting with central airway obstruction, safely and effectively treated with cryoextraction of the tumour using flexible bronchoscopy.

Comparative effectiveness of intensity modulated radiation therapy to 3-dimensional conformal radiation in locally advanced lung cancer: pathological and clinical outcomes.

OBJECTIVE: Intensity-modulated radiotherapy (IMRT) has better normal-tissue sparing compared with 3-dimensional conformal radiation (3DCRT). We sought to assess the impact of radiation technique on pathological and clinical outcomes in locally advanced non-small cell lung cancer (LANSCLC) treated with a trimodality strategy. METHODS: Retrospective review of LANSCLC patients treated from August 2012 to August 2018 at Sheba Medical Center, Israel. The trimodality strategy consisted of concomitant chemoradiation to 60 Gray (Gy) followed by completion surgery. The planning target volume (PTV) was defined by co-registered PET/CT. Here we compare the pathological regression, surgical margin status, local control rates (LC), disease free (DFS) and overall survival (OS) between 3DCRT and IMRT. RESULTS: Our cohort consisted of 74 patients with mean age 62.9 years, male in 51/74 (69%), adenocarcinoma in 46/74 (62.1%), stage 3 in 59/74 (79.7%) and chemotherapy in 72/74 (97.3%). Radiation mean dose: 59.2 Gy (SD ± 3.8). Radiation technique : 3DCRT in 51/74 (68.9%), IMRT in 23/74 (31%). Other variables were similar between groups.Major pathological response (including pathological complete response or less than 10% residual tumor cells) was similar: 32/51 (62.7%) in 3DCRT and 15/23 (65.2%) in IMRT, p=0.83. Pathological complete response (pCR) rates were similar: 17/51 (33.3%) in 3DCRT and 8/23 (34.8%) in IMRT, p=0.9. Surgical margins were negative in 46/51 (90.1%) in 3DCRT vs. 17/19 (89.4%) in IMRT (p=1.0).The 2-year LC rates were 81.6% (95% CI 69-89.4%); DFS 58.3% (95% CI 45.5-69%) and 3-year OS 70% (95% CI57-80%). Comparing radiation techniques, there were no significant differences in LC (p=0.94), DFS (p=0.33) and OS (p=0.72). CONCLUSION: When used to treat LANSCLC in the neoadjuvant setting, both IMRT and 3DCRT produce comparable pathological and clinical outcomes. ADVANCES IN KNOWLEDGE: This study validates the real-world effectiveness of IMRT compared to 3DCRT.

Study of the effect of the herbal composition SR2004 on hemoglobin A1c, fasting blood glucose, and lipids in patients with type 2 diabetes mellitus.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by raised blood glucose levels and peripheral insulin resistance. It is an increasingly prevalent global healthcare concern. Conventional treatment options are limited and in this context, there is renewed interest in evaluating the clinical and biological effects of traditional therapies. We assess the effect of a new herbal composition SR2004 on the hemoglobin A1c (HbA1c), fasting blood glucose, and lipid profiles of patients with T2DM. METHODS: This is a single center, unblinded, prospective interventional study conducted in Israel. The composition SR2004 includes Morus alba, Artemisia dracunculus, Urtica dioica, Cinnamomum zeylanicum, and Taraxacum officinale. One hundred and nineteen patients with diagnosed T2DM were enrolled and received SR2004 in addition to their usual medications. HbA1c, fasting blood glucose, and lipid profiles at 12 weeks were compared with baseline. In addition, the tolerability and side effects of SR2004 were recorded. RESULTS: One hundred and three patients completed 12 weeks of follow-up (87%) and were included in the results. At 12 weeks, HbA1c reduced from 9.0% to 7.1% (22%; p < 0.0001), mean blood glucose decreased from 211 mg/dL to 133 mg/dL (37% reduction; p < 0.0001), mean total cholesterol to 185 mg/dL (13% reduction; p < 0.01) and mean serum triglycerides to160 mg/dL (a reduction of 40% from baseline; p < 0.001). Twelve patients (12%) had no response with SR2004 supplementation. In addition, of thirteen patients who took insulin at baseline, five required only oral hypoglycemics and another five reduced their daily insulin requirements by 30% at 12 weeks. Clinical observations included improvements in vasculopathy, including reversal of established retinopathic changes in two patients.No major adverse effects were observed, with minor abdominal symptoms reported in sixteen patients (16%). CONCLUSION: SR2004 supplementation significantly reduced HbA1c, blood glucose, and lipids with good tolerability and no observed adverse interactions with conventional medications. Some interesting findings relating to the reversal of microvascular phenomena warrant further research to elucidate the mechanisms of action of this novel composition.

Safety and Efficacy of Tissue Plasminogen Activator and DNase for Complicated Pleural Effusions Secondary to Abdominal Pathology.

RATIONALE: Exudative pleural effusions may arise secondary to inflammation of intra-abdominal structures. Pleural space loculations can complicate these effusions, preventing adequate chest tube drainage and leading to consideration of surgical intervention. Previous studies have demonstrated that intrapleural administration of tissue plasminogen activator (tPA) combined with human recombinant DNase can improve fluid drainage and reduce surgery for patients with loculated parapneumonic effusions; however, the efficacy of this treatment has not been evaluated for complicated pleural effusions attributed to intra-abdominal inflammation. OBJECTIVES: We assessed the safety and efficacy of tPA/DNase for 17 pleural effusions associated with nonmalignant intra-abdominal pathology that did not drain adequately after placement of one or more chest tubes. METHODS: Efficacy was measured by comparing post- to pretreatment fluid drainage rates, volumetric assessment of pleural fluid on radiographic images before and after treatment, and clinical improvement, including the need for surgical intervention. Symptomatic relief was assessed using the Borg scale for breathlessness. MEASUREMENTS AND MAIN RESULTS: After a median of two doses of tPA/DNase, 23.5% of patients had chest pain and none had pleural bleeding. The volume of pleural fluid drained increased from a median of 325 ml to 890 ml per 24 hours after therapy (P = 0.018). The area of pleural space opacity on chest radiographs decreased from a median of 42.8-17.8% of the hemithorax (P = 0.001). tPA/DNase reduced the pleural fluid volume on chest computed tomographic imaging from a median of 294.4 ml to 116.1 ml. Borg scores improved from a median of 3 (interquartile range = 1-6) to 0 (interquartile range = 0-2) after therapy (P = 0.001). The median duration of chest tube placement and hospital stay were 4 and 11 days, respectively. Two patients required surgical intervention for lung entrapment. Overall, treatment was considered successful for 88.2% of patients. CONCLUSIONS: This retrospective case series suggests that intrapleural tPA/DNase can be safe and effective for patients with complicated pleural effusions attributed to abdominal pathology that do not drain adequately after chest tube placement. Additional studies are needed to determine whether the combination of tPA and DNase is more effective than tPA for this indication.

Concurrent Intrapleural Instillation of Tissue Plasminogen Activator and DNase for Pleural Infection. A Single-Center Experience.

RATIONALE: Treatment of pleural infection with instillation of intrapleural tissue plasminogen activator (tPA) and human recombinant DNase (DNase) has been proven to decrease the length of hospital stay, decrease surgical referral, and improve drainage. The optimal dosage, administration, timing, and frequency of the regimen remain unclear. It is unknown if the two drugs can be administered immediately one after the other (referred to as concurrent) instead of instilling them separately with a 1- to -2-hour interval in between. OBJECTIVES: To assess the safety and efficacy of concurrent instillation of intrapleural tPA/DNase guided by radiographic and clinical response in patients with pleural infection. METHODS: We conducted a retrospective cohort study. Consecutive patients with pleural infection who received concurrent tPA/DNase were included. The initiation and number of doses of tPA/DNase therapy were based on pleural fluid drainage, clinical response, and radiographic findings. MEASUREMENTS AND MAIN RESULTS: Seventy-three patients received concurrent tPA/DNase therapy. Treatment was successful in 90.4% of them; 80.8% were effectively treated with fewer than six doses of therapy (median, 2; interquartile range [IQR], 1-3.5); and 71.2% received their first dose of tPA/DNase within 24 hours after chest tube insertion. The median hospital stay from the first dose of tPA/DNase to discharge was 7 days (IQR, 5-11 d). The volume of pleural fluid drained increased from a median of 295 ml (IQR, 97.5-520 ml) 24 hours before treatment to a median of 1,102 ml (IQR, 627-2,200 ml) 72 hours following therapy (P < 0.001). Nonfatal pleural bleeding occurred in 5.4%, 15.1% had chest pain, and 2.7% died as a result of pleural infection. CONCLUSIONS: This cohort study shows that early administration of concurrent tPA/DNase in patients with pleural infection is relatively safe and effective. Given the high cost of therapy, it is feasible to guide therapy on the basis of clinical and radiographic response.

Unimodality and Multimodality Cryodebridement for Airway Obstruction. A Single-Center Experience with Safety and Efficacy.

RATIONALE: Cryodebridement (CD) refers to the removal of obstructive material from the lumen of the tracheobronchial tree by freezing with a cryoprobe, which is usually inserted through a flexible bronchoscope. This method of achieving instant recanalization of airways has been established for over 20 years, but published experience comprises limited case series. OBJECTIVES: This study describes a single large-volume referral center experience, including clinical outcomes and safety profile. METHODS: Electronic medical records of 156 patients who underwent bronchoscopic CD between December 2007 and March 2012 as the primary method to relieve airway obstruction were reviewed retrospectively. MEASUREMENTS AND MAIN RESULTS: The most frequent cause of airway obstruction was malignancy (n = 88), with non-small-cell lung cancer and metastatic renal cell carcinoma being the most common etiologies. The site of obstruction was localized to the central airways in 63 patients (40%) and the distal airways in 44 patients (28%), and it was diffuse in 49 patients (32%). Bronchoscopic airway patency was achieved in 95% of patients, with the highest success rates found in those with obstruction localized in the central airways. Improvement in symptoms occurred in 118 (82%) of 144 symptomatic patients. Serious complications were reported in 17 patients (11%) and included respiratory distress, severe bleeding, airway injury, and hemodynamic instability. All patients responded to treatment, and no intra- or postoperative deaths were reported. CONCLUSIONS: CD, when used alone or in combination with other endoscopic treatment modalities, appears to be safe and effective in treating endoluminal airway obstruction.