Combined-modality therapy for pulmonary alveolar proteinosis in a remote setting: a case report.

BACKGROUND: Pulmonary alveolar proteinosis (PAP) is a rare lung disease characterized by accumulation of phospholipoproteinaceous material in the alveoli. The presentation is nonspecific but typically includes dyspnea; the spectrum of disease includes rapidly progressive hypoxic respiratory failure. Whole lung lavage (WLL) is the treatment of choice in symptomatic PAP, but transient worsening of oxygenation sometimes requires salvage modalities of support such as extracorporeal membrane oxygenation (ECMO). Granulocyte macrophage colony-stimulating factor (GM-CSF) plays a role in the pathophysiology of PAP. We highlight a case of severe PAP treated with exogenous GM-CSF and sequential lobar lavage due to the unavailability of salvage methods of oxygenation. CASE PRESENTATION: A 36 year old female was admitted with fevers, chills, and progressive dyspnea. On presentation she was tachypneic, tachycardic, and hypoxemic; labs revealed leukocytosis and lactic acidosis. Chest CT identified diffuse ground glass opacities in a 'crazy-paving' pattern. Following intubation due to impending respiratory failure, bronchoscopy with bronchoalveolar lavage was performed. The lavage return stained positive with Periodic Acid Schiff, confirming the diagnosis of PAP. Continued deterioration necessitated treatment; however, at this geographically remote center without ECMO services WLL was judged to carry significant risk. Nebulized GM-CSF was administered without significant improvement. Subcutaneous GM-CSF was administered and isolated subsegmental lavages of the bilateral upper lobes were performed, with rapid improvement in oxygenation. Additional sequential lobar lavage and continued GM-CSF therapy as an outpatient resulted in complete resolution of oxygen requirement and return to normal pulmonary physiology. CONCLUSIONS: The autoimmune form of PAP is the most common, indicating that therapy with GM-CSF may play an important role for many patients. Treatment with WLL may be impractical in some clinical settings due to the expertise and salvage modalities required. Sequential lobar lavage requires less specialized expertise and may incur less risk of refractory hypoxemia. We posit that this combined-modality therapy is ideally suited to geographically-remote centers such as our own.

Endobronchial ultrasound bronchoscopy Franseen fine needle biopsy tool versus standard fine needle aspiration needle: Impact on diagnosis and tissue adequacy.

BACKGROUND: The Franseen fine needle biopsy tool (Acquire®, Boston Scientific, Boston, MA) may provide better quality specimens than current endobronchial ultrasound-transbronchial needle aspiration (EBUS-TNBA) needles. We performed a comparative retrospective study evaluating the diagnostic yield of the Franseen fine needle biopsy (FNB) versus standard fine needle aspiration (FNA) for benign lymphadenopathy and tissue acquisition for next generation sequencing (NGS) in non-small cell carcinoma (NSCLC). METHODS: All EBUS-TBNA procedures performed between January 1st, 2019 to January 1st, 2020 where both the FNB needle and the FNA needle were used were analyzed. All demographic, procedural, and diagnostic data were recorded. The median tumor surface area, tumor cellularity and adequacy for NGS was evaluated for NSCLC specimens. RESULTS: A total of 69 target lesions in 66 patients were biopsied with both the FNB and FNA needles. The mean (SD) size of target biopsied was 1.8 cm (0.8); The most common stations were 7 (54%) and 4R (26%). The mean (SD) needle passes were 6 (2.2) and 4 (1.8) with FNA and FNB needles, respectively (p < 0.0001). Benign lymphadenopathy was diagnosed with FNA needle in 46% and in 82% with FNB (p < 0.0001). NGS tissue adequacy was 47% with FNA needle versus 76% with FNB (p = 0.02). Median tumor surface area and tumor cellularity were greater with FNB needle than FNA needle (80 mm2 versus 9 mm2, p = 0.002, and 81% versus 45%, p = 0.0004). CONCLUSION: The FNB needle demonstrated higher diagnostic yield in benign lymphadenopathy and higher quality for NGS than standard FNA needle.

A 40-Year-Old Man With Multiple Pulmonary Nodules and Mediastinal Lymphadenopathy With Positive Anti-Neutrophil Cytoplasmic Antibody Reveals an Unexpected Diagnosis.

CASE PRESENTATION: A 40-year-old man with no significant medical history presented to the ED with a 2-day history of right-sided chest pain accompanied by night sweats and chills. These symptoms were accompanied by a dry, nonproductive cough without hemoptysis. The patient worked as an air traffic controller, with a side business of buying, renovating, and selling houses. He takes part in the remodeling work himself but denies any exposure to animal droppings, bird droppings, or mold. He denied chronic sinus disease, rash, or arthralgias. A resident of Platte City, Missouri, he had recently traveled to Salt Lake City, Utah. At the time of presentation, the patient denied any fever or shortness of breath. He had no history of nicotine, alcohol, or illicit substance use and denied any recent weight loss.

Shape-Sensing Robotic-Assisted Bronchoscopy vs Digital Tomosynthesis-Corrected Electromagnetic Navigation Bronchoscopy: A Comparative Cohort Study of Diagnostic Performance.

BACKGROUND: Electromagnetic navigational bronchoscopy has been the dominant bronchoscopic technology for targeting small peripheral lesions and now includes digital tomosynthesis-electromagnetic navigational bronchoscopy (DT-ENB), allowing near-real-time intraprocedural nodule visualization. Shape-sensing robotic-assisted bronchoscopy (ssRAB), with improved catheter stability and articulation recently became available. Although the diagnostic performance of these two methods seems higher than that of legacy systems, data remain limited. We sought to compare the diagnostic yield of these two novel platforms after their introduction at our institution. RESEARCH QUESTION: Does the diagnostic yield of ssRAB differ significantly from that of DT-ENB in patients undergoing biopsy of peripheral pulmonary lesions (PPLs)? STUDY DESIGN AND METHODS: This retrospective comparative cohort study analyzed prospectively collected data on consecutive procedures performed with DT-ENB and ssRAB in their first 6 months of use at our institution. Biopsies were considered diagnostic if histopathologic analysis revealed malignancy or specific benign features that readily explained the presence of a PPL. Nonspecific inflammation, normal lung or airway, and atypia not diagnostic of malignancy were considered nondiagnostic. RESULTS: SSRAB was used to biopsy 143 PPLs in 133 patients and DT-ENB was used to biopsy 197 PPLs in 170 patients. Diagnostic yield was 77% for ssRAB (110 of 143 PPLs) and 80% (158 of 197 PPLs) for DT-ENB (OR, 0.8; 95% CI, 0.5-1.4; P = .4). Median lesion diameters were 17 and 19 mm, respectively. No difference in diagnostic yield was found after adjustment for lesion size, bronchus sign, peripheral vs middle third location, and sex. Pneumothorax complicated 1.5% of ssRAB and 1.8% of DT-ENB procedures (P = .86). INTERPRETATION: SSRAB and DT-ENB showed comparable diagnostic yields and safety profiles in this comparative cohort study.

Navigational Bronchoscopy versus Computed Tomography-guided Transthoracic Needle Biopsy for the Diagnosis of Indeterminate Lung Nodules: protocol and rationale for the VERITAS multicenter randomized trial.

Background: Lung nodule incidence is increasing. Many nodules require biopsy to discriminate between benign and malignant etiologies. The gold-standard for minimally invasive biopsy, computed tomography-guided transthoracic needle biopsy (CT-TTNB), has never been directly compared to navigational bronchoscopy, a modality which has recently seen rapid technological innovation and is associated with improving diagnostic yield and lower complication rate. Current estimates of the diagnostic utility of both modalities are based largely on non-comparative data with significant risk for selection, referral, and publication biases. Methods: The VERITAS trial (na V igation E ndoscopy to R each Indeterminate lung nodules versus T ransthoracic needle A spiration, a randomized controlled S tudy) is a multicenter, 1:1 randomized, parallel-group trial designed to ascertain whether electromagnetic navigational bronchoscopy with integrated digital tomosynthesis is noninferior to CT-TTNB for the diagnosis of peripheral lung nodules 10-30 mm in diameter with pre-test probability of malignancy of at least 10%. The primary endpoint is diagnostic accuracy through 12 months follow-up. Secondary endpoints include diagnostic yield, complication rate, procedure duration, need for additional invasive diagnostic procedures, and radiation exposure. Discussion: The results of this rigorously designed trial will provide high-quality data regarding the management of lung nodules, a common clinical entity which often represents the earliest and most treatable stage of lung cancer. Several design challenges are described. Notably, all nodules are centrally reviewed by an independent interventional pulmonology and radiology adjudication panel relying on pre-specified exclusions to ensure enrolled nodules are amenable to sampling by both modalities while simultaneously protecting against selection bias favoring either modality. Conservative diagnostic yield and accuracy definitions with pre-specified criteria for what non-malignant findings may be considered diagnostic were chosen to avoid inflation of estimates of diagnostic utility. Trial registration: ClinicalTrials.gov NCT04250194.

Cryobiopsy With Radial UltraSound Guidance (CYRUS): A Pilot Randomized Controlled Study.

BACKGROUND: Major airway bleeding is the most feared complication of transbronchial cryobiopsy (TBC). Radial endobronchial ultrasound (REBUS) has been used to assess the peripheral lung, primarily to identify pulmonary nodules, and also peripheral blood vessels. Using REBUS-guided TBC to avoid peripheral vasculature might reduce bleeding risk. This prospective randomized double-blind pilot trial was designed to investigate the feasibility of study procedures and inform the power calculation and clinical significance of a future large randomized trial. METHODS: Consecutive TBCs were randomized to be performed with or without REBUS guidance in the same patient. A nonblinded operator obtained each biopsy while a blinded second operator managed the bleeding after each biopsy and determined when hemostasis had been obtained. Feasibility of study procedures and the ability to recruit patients were of primary interest. Time to hemostasis after each biopsy was also examined. RESULTS: Forty TBCs were performed in 10 patients (4 biopsies per patient) over an enrollment period of 6 months. The time to control bleeding between biopsies was not statistically different between intervention and control arms [-14.3 (-120.1 to 92.0) s, P=0.7878]. Mean bleeding time was 139.4±59.895 seconds (REBUS 132.25± 89.305 s, non-REBUS 146.55±82.043 s). A trend towards the decreased grade of bleeding and less need for additional interventions was observed with REBUS use, but this difference did not reach statistical significance in this pilot investigation. CONCLUSION: Our findings suggest that REBUS-guided TBC is feasible. We did not observe any statistically significant difference in time to hemostasis or bleeding grade in this pilot study.

Effect of pentoxifylline on GFR decline in CKD: a pilot, double-blind, randomized, placebo-controlled trial.

BACKGROUND: Pentoxifylline is a nonspecific phosphodiesterase inhibitor with anti-inflammatory properties. It reduces proteinuria in patients with glomerular disease, although its impact on glomerular filtration rate (GFR) is unknown. We hypothesized that pentoxifylline would slow the estimated GFR decrease in patients with chronic kidney disease at high risk of progression. STUDY DESIGN: Pilot randomized double-blind placebo-controlled trial. SETTING & PARTICIPANTS: 40 outpatients with decreased GFR, hypertension, and proteinuria greater than 1 g/24 h currently treated with angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or the combination and followed up in a nephrology clinic at a tertiary medical care facility. INTERVENTION: Pentoxifylline, 400 mg twice daily, or matching placebo. OUTCOMES: Difference in rates of estimated GFR change during the 1-year study period between the 2 groups. MEASUREMENTS: Estimated GFR (4-variable Modification of Diet in Renal Disease Study equation) and proteinuria by 24-hour urine collection were assessed at baseline and 6 and 12 months after enrollment. RESULTS: Baseline characteristics were similar between the 2 groups. At 1 year, the mean estimated GFR decrease was significantly less in the pentoxifylline group than the placebo group (-1.2 +/- 7.0 versus -7.2 +/- 8.2 mL/min/1.73 m2/y; mean difference, -6.0 mL/min/1.73 m2/y; 95% confidence interval, -11.4 to -0.6; P = 0.03). For pentoxifylline-treated participants, the mean estimated GFR decrease during treatment was slower compared with the year before study enrollment (-9.6 +/- 11.9 mL/min/1.73 m2/y; mean difference, -8.4 mL/min/1.73 m2/y; 95% confidence interval, -14.8 to -2.1; P = 0.01). Proteinuria was not different between the pentoxifylline and placebo groups at baseline, 6 months, or 1 year. LIMITATIONS: Small sample size and incomplete follow-up. CONCLUSIONS: Pentoxifylline may slow the estimated GFR decrease in high-risk patients. This may be independent of its antiproteinuric properties and warrants further investigation.

Hyperkalemia after packed red blood cell transfusion in trauma patients.

BACKGROUND: Published analyses of clinical outcomes for patients requiring large-volume blood transfusion conflict with respect to the impact upon plasma potassium levels. We analyzed a cohort of trauma patients to ascertain the impact of component product transfusion upon plasma potassium values. METHODS: We performed an observational analysis of previously, prospectively collected clinical data on 131 noncrush trauma patients undergoing resuscitation during the initial 12 hours after admission to a combat support hospital. Comparisons were made between those who received packed red blood cell (PRBC) transfusion and those who did not. Primary outcome was hyperkalemia (plasma potassium level >5.5 mmol/L). RESULTS: Ninety-six of one hundred thirty-one patients (73.3%) received PRBCs (mean number of PRBC units 11.2, range, 0-55.0). For transfusion versus nontransfusion patients, baseline plasma potassium value (3.7 +/- 0.57 mmol/L vs. 3.6 +/- 0.36 mmol/L, p = 0.22) rose significantly after transfusion (5.3 +/- 1.2 mmol/L, vs. 4.0 +/- 0.78 mmol/L, p < 0.001). During the study period, 38.5% of transfusion patients developed hyperkalemia, versus 2.9% of those who did not (p = 0.003). In multivariate logistic regression analysis, transfusion of greater than 7 units of PRBCs was independently associated with the development of hyperkalemia (RR 4.72, 95% CI 1.01-21.97, p = 0.048). Transfusion of other cell-based products, baseline base deficits, and plasma bicarbonate levels were not. Spearman's rank correlation coefficient for the relationship of number of transfused PRBC units to the highest recorded potassium value was 0.554 (p < 0.001). The predictive accuracy of the logistic regression model for hyperkalemia was 0.824 (95% CI 0.747-0.901, p < 0.001). CONCLUSIONS: Hyperkalemia is common after PRBC transfusion, and often severe. PRBC transfusion is independently associated with the development of hyperkalemia. The findings suggest the need for interventional studies examining the impact of alternative resuscitative approaches after severe trauma.

Resuscitative hyperkalemia in noncrush trauma: a prospective, observational study.

The trauma patient is exposed to physiologic processes and life-saving interventions that predispose to hyperkalemia. Severe elevations in potassium levels subject this compromised patient to additional cardiac risks in the periresuscitative period. Recent advances in the care of the massively traumatized patient may or may not increase the risk for hyperkalemia. This prospective, observational study was undertaken to define the period prevalence of hyperkalemia (plasma potassium level > or = 5.5 mmol/L) in a noncrush trauma population during the initial resuscitative period and to identify potential risk factors for the development of hyperkalemia. A total of 131 patients were studied during the initial 12 h after admission for noncrush trauma. The period prevalence of hyperkalemia was 29.0%. Hyperkalemic patients had dramatic shifts in plasma potassium levels compared with nonhyperkalemic patients. Five patients, all from the hyperkalemic group, died. By multivariate logistic regression analysis, independent risk factors for hyperkalemia were an emergency department plasma potassium level of 4.0 mmol/L or higher (relative risk 3.40; 95% confidence interval 1.17 to 9.84; P = 0.024 versus baseline potassium level < 4.0 mmol/L) and transfusion of cell- or plasma-based products (relative risk 10.56; 95% confidence interval 3.62 to 30.78; P < 0.001 per log-transformed unit). The prevalence of hyperkalemia during trauma resuscitation was not reported previously. Given the arrhythmic risks of hyperkalemia, particular caution is necessary with trauma patients who present with plasma potassium levels > 4.0 mmol/L and require aggressive transfusion support.