Abubakr A. Bajwa

Safety and efficacy of transition from systemic prostanoids to inhaled treprostinil in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a disease characterized by increased pulmonary pressures and chronic right heart failure. Therapies for moderate and severe PAH include subcutaneous (SQ) and intravenous (IV) prostanoids that improve symptoms and quality of life. However, treatment compliance can be limited by severe side effects and complications related to methods of drug administration. Inhaled prostanoids, which offer the advantage of direct delivery of the drug to the pulmonary circulation without need for invasive approaches, may serve as an alternative for patients unable to tolerate SQ/IV therapy. In this retrospective cohort study we collected clinical, hemodynamic, and functional data from 18 clinically stable patients with World Health Organization group I PAH seen in 6 large national PAH centers before and after transitioning to inhaled treprostinil from IV/SQ prostanoids. Before transition 15 patients had been receiving IV or SQ treprostinil (mean dose 73 ng/kg/min) and 3 patients had been on IV epoprostenol (mean dose 10 ng/kg/min) for an average duration of 113 ± 80 months. Although most patients who transitioned to inhaled treprostinil demonstrated no statistically significant worsening of hemodynamics or 6-minute walk distance, a minority demonstrated worsening of New York Heart Association functional class over a 7-month period. In conclusion, although transition of patients from IV/SQ prostanoids to inhaled treprostinil appears to be well tolerated in clinically stable patients, they should remain closely monitored for signs of clinical decompensation.

Proton Therapy With Concurrent Chemotherapy for Non–Small-Cell Lung Cancer: Technique and Early Results

BACKGROUND Proton therapy can deliver a more conformal dose distribution than photon radiation and may allow safe dose escalation in stage III lung cancer. Early outcomes are presented here for patients who received proton therapy with concurrent chemotherapy for non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS Nineteen patients with regionally advanced NSCLC were treated with concurrent chemotherapy (carboplatin and paclitaxel [n = 18]) and proton therapy from August 2008 to April 2010 either with (n = 7) or without (n = 12) induction chemotherapy. Eighteen patients had stage III NSCLC, and 1 patient had stage IIB disease. The median proton therapy dose was 74 cobalt gray equivalent (CGE) in 2 CGE fractions with 18 patients who received ≥70 CGE. Twelve patients also received selective nodal proton therapy to the adjacent uninvolved nodal regions, with a median dose of 40 CGE (range, 40-46 CGE). The patients were routinely evaluated for treatment-related toxicity and disease progression every 3 months, with a history, physical, and computed tomography or positron emission tomography-computed tomography. RESULTS The median follow-ups for living patients were 15 and 16 months (range, 7-26 months), respectively. Nonhematologic and hematologic acute grade 3+ toxicity (<90 days) developed in 1 and 4 patients, respectively. Two of 16 patients assessable for late toxicity (≥90 days) developed a significant grade 3+ nonhematologic late toxicity, whereas 1 patient developed a grade 3+ hematologic late toxicity. Local progression was the site of first relapse in one patient. CONCLUSION Mediastinal proton therapy with concomitant chemotherapy was associated with acceptable toxicity. Although encouraging, longer follow-up with more patients is needed to confirm the long-term efficacy of this treatment.

Automated prone positioning and axial rotation in critically ill, nontrauma patients with acute respiratory distress syndrome (ARDS).

The objective of this study was to evaluate the use of kinetic therapy beds for automated prone positioning and axial rotation in critically ill nontrauma patients with acute respiratory distress syndrome (ARDS). There were 17 patients with ARDS who underwent automated prone positioning using a kinetic therapy bed. The mean age was 51 + 14 years; 12 were females and 12 were Caucasian. The most common admission diagnosis was sepsis (n = 5). The mean Acute Physiology and Chronic Health Evaluation (APACHE) 2 score was 30 + 9 with mean predicted mortality of 65% + 25%. At the time of prone positioning, all patients met the criteria for ARDS. The mean ratio of PaO2 to FIO2 (P/F ratio) before initiation of prone positioning was 89 + 33 and rose to 224 + 92 after at least 30 minutes of prone positioning (P < .0001). There was no significant change in PaCO2 or mean airway pressure. There were no instances of accidental endotracheal tube and central or peripheral venous or arterial catheter dislodgement. Eleven (65%) patients developed new pressure ulcers, 10 (59%) patients developed new skin tears, and all had conjunctival edema during the course of prone positioning. The median duration of automated prone positioning was 6 (interquartile range [IQR] 3.5-8.5) days. Eleven (65%) patients died during hospitalization and 7 required percutaneous tracheostomy for long-term ventilator support. Automated prone positioning using a kinetic therapy bed is a safe and effective means of improving oxygenation in critically ill patients with ARDS. Larger randomized studies are needed to compare it to conventional ventilation strategies, conventional prone positioning, and to assess the impact on mortality.

A Phase 2 Trial of Concurrent Chemotherapy and Proton Therapy for Stage III Non-Small Cell Lung Cancer: Results and Reflections Following Early Closure of a Single-Institution Study

PURPOSE Proton therapy has been shown to reduce radiation dose to organs at risk (OAR) and could be used to safely escalate the radiation dose. We analyzed outcomes in a group of phase 2 study patients treated with dose-escalated proton therapy with concurrent chemotherapy for stage 3 non-small cell lung cancer (NSCLC). METHODS AND MATERIALS From 2009 through 2013, LU02, a phase 2 trial of proton therapy delivering 74 to 80 Gy at 2 Gy/fraction with concurrent chemotherapy for stage 3 NSCLC, was opened to accrual at our institution. Due to slow accrual and competing trials, the study was closed after just 14 patients (stage IIIA, 9 patients; stage IIIB, 5 patients) were accrued over 4 years. During that same time period, 55 additional stage III patients were treated with high-dose proton therapy, including 7 in multi-institutional proton clinical trials, 4 not enrolled due to physician preference, and 44 who were ineligible based on strict entry criteria. An unknown number of patients were ineligible for enrollment due to insurance coverage issues and thus were treated with photon radiation. Median follow-up of surviving patients was 52 months. RESULTS Two-year overall survival and progression-free survival rates were 57% and 25%, respectively. Median lengths of overall survival and progression-free survival were 33 months and 14 months, respectively. There were no acute grade 3 toxicities related to proton therapy. Late grade 3 gastrointestinal toxicity and pulmonary toxicity each occurred in 1 patient. CONCLUSIONS Dose-escalated proton therapy with concurrent chemotherapy was well tolerated with encouraging results among a small cohort of patients. Unfortunately, single-institution proton studies may be difficult to accrue and consideration for pragmatic and/or multicenter trial design should be considered when developing future proton clinical trials.

Dosimetric rationale and early experience at UFPTI of thoracic proton therapy and chemotherapy in limited-stage small cell lung cancer

Abstract Background. Concurrent chemoradiotherapy (CRT) is the standard of care in patients with limited-stage small cell lung cancer (SCLC). Treatment with conventional x-ray therapy (XRT) is associated with high toxicity rates, particularly acute grade 3+ esophagitis and pneumonitis. We present outcomes for the first known series of limited-stage SCLC patients treated with proton therapy and a dosimetric comparison of lung and esophageal doses with intensity-modulated radiation therapy (IMRT). Material and methods. Six patients were treated: five concurrently and one sequentially. Five patients received 60–66 CGE in 30–34 fractions once daily and one patient received 45 CGE in 30 fractions twice daily. All six patients received prophylactic cranial irradiation. Common Terminology Criteria for Adverse Events, v3.0, was used to grade toxicity. IMRT plans were also generated and compared with proton plans. Results. The median follow-up was 12.0 months. The one-year overall and progression-free survival rates were 83% and 66%, respectively. There were no cases of acute grade 3+ esophagitis or acute grade 2+ pneumonitis, and no other acute grade 3+ non-hematological toxicities were seen. One patient with a history of pulmonary fibrosis and atrial fibrillation developed worsening symptoms four months after treatment requiring oxygen. Three patients died: two of progressive disease and one after a fall; the latter patient was disease-free at 36 months after treatment. Another patient recurred and is alive, while two patients remain disease-free at 12 months of follow-up. Proton therapy proved superior to IMRT across all esophageal and lung dose volume points. Conclusion. In this small series of SCLC patients treated with proton therapy with radical intent, treatment was well tolerated with no cases of acute grade 3+ esophagitis or acute grade 2+ pneumonitis. Dosimetric comparison showed better sparing of lung and esophagus with proton therapy. Proton therapy merits further investigation as a method of reducing the toxicity of CRT.

The relationship of intravenous fluid chloride content to kidney function in patients with severe sepsis or septic shock

BACKGROUND Previous studies suggest a relationship between chloride-rich intravenous fluids and acute kidney injury in critically ill patients. OBJECTIVES The aim of this study was to evaluate the relationship of intravenous fluid chloride content to kidney function in patients with severe sepsis or septic shock. METHODS A retrospective chart review was performed to determine (1) quantity and type of bolus intravenous fluids, (2) serum creatinine (Cr) at presentation and upon discharge, and (3) need for emergent hemodialysis (HD) or renal replacement therapy (RRT). Linear regression was used for continuous outcomes, and logistic regression was used for binary outcomes and results were controlled for initial Cr. The primary outcome was change in Cr from admission to discharge. Secondary outcomes were need for HD/RRT, length of stay (LOS), mortality, and organ dysfunction. RESULTS There were 95 patients included in the final analysis; 48% (46) of patients presented with acute kidney injury, 8% (8) required first-time HD or RRT, 61% (58) were culture positive, 55% (52) were in shock, and overall mortality was 20% (19). There was no significant relationship between quantity of chloride administered in the first 24 hours with change in Cr (β = -0.0001, t = -0.86, R(2) = 0.92, P = .39), need for HD or RRT (odds ratio [OR] = 0.999; 95% confidence interval [CI], 0.999-1.000; P = .77), LOS >14 days (OR = 1.000; 95% CI, 0.999-1.000; P = .68), mortality (OR = 0.999; 95% CI, 0.999-1.000; P = .88), or any type of organ dysfunction. CONCLUSION Chloride administered in the first 24 hours did not influence kidney function in this cohort with severe sepsis or septic shock.

Proton therapy for lung cancer

Proton therapy is an emerging radiotherapy technology with the potential to improve the therapeutic index in the treatment of lung cancer patients. Since charged particles, such as protons, have a penetration length that can be modified by using different energies, protons offer the clinician the ability to modulate radiation dose deposition along the beam path. This facilitates an increase of the dose to the tumor target while minimizing the volume of normal tissue irradiation. Such precise delivery is particularly relevant in the setting of lung cancer where the targeted tissues are in close proximity to moderately radiation‐sensitive organs like the spinal cord, heart, and esophagus, but are also effectively surrounded by the normal lung, which is extremely sensitive to radiation damage. Proton therapy has been investigated for the treatment of surgically curable yet medically inoperable patients as well as patients with regionally advanced disease.

A 62-Year-Old Woman With Dyspnea, Leukocytosis, and Diffuse Ground-Glass Opacities

62-year-old female presented to the ambulatory clinic with progressive shortness of breath over the course of approximately 1 year. She denied cough, fever, chills, chest pain, hemoptysis, or orthopnea. Approximately 1 year before presentation, she was admitted to the hospital for abdominal pain, distention, and early satiety. At that time she was diagnosed with chronic idiopathic myelofi brosis after bone marrow biopsy. She responded well on hydroxyurea and eventually discharged home. She also denied any occupational or environmental exposures prior to presentation.

Predicting the Need for Upfront Combination Therapy in Pulmonary Arterial Hypertension

Background: Combination therapy is commonly used for pulmonary arterial hypertension (PAH) treatment. We aimed to identify factors that may predict the need for future combination therapy. Methods: We conducted a retrospective chart review of consecutive patients with PAH in an aim to describe baseline clinical, echocardiogram, and hemodynamic characteristics of patients who eventually required combination therapy during the course of their disease and compared them to the ones who were maintained on monotherapy. Results: The monotherapy group was followed for an average of 31.8 ± 18.8 months and the combination therapy group was followed for an average of 28.7 ± 13.6 months. Among the 71 patients analyzed, a significantly higher number of patients who eventually required combination therapy belonged to World Health Organization functional class 3 (45% vs 37%) and 4 (23% vs 0) at baseline, compared with those on monotherapy (P < .05). Combination group also had a higher Registry to Evaluate Early And Long-term PAH Disease Management (REVEAL) PAH risk score at presentation. End of 6-minute walk test (6MWT), oxygen saturation (Spo 2) was also lower in the combination therapy group, 86% ± 8% versus 91% ± 7% (P < .05). Patients who eventually required combination therapy were more frequently noticed to have right ventricular enlargement, right atrial enlargement, and had a higher resting estimated right ventricular systolic pressure (RVSP). Right heart catheterization-derived hemodynamics data at baseline showed that the combination therapy group had a higher mean pulmonary artery (PA) pressure, lower pulmonary capillary wedge pressure, lower cardiac output, and higher pulmonary vascular resistance (PVR). On univariate analysis, only PVR ≥300 dyne·s/cm5, mean PA pressure of ≥40 mm Hg, estimated RVSP ≥ 60 mm Hg, PAH risk score ≥ 10, and end of 6MWT saturation of ≤ 90% were of significance. Conclusion: Patients with PAH who require combination therapy in the course of their disease have worse hemodynamics, PAH risk score, functional class, and end of 6MWT oxygen saturation at the time of presentation compared to patients maintained on monotherapy.

A case of disseminated intravascular coagulation secondary to Acinetobacter lwoffii and Acinetobacter baumannii bacteremia

Bacteremia is currently one of the infections with the highest mortality in hospitals [1]. Acinetobacter lwoffii and Acinetobacter baumannii are gram-negative bacteria and both represent opportunistic pathogens. In certain cases, the management can be challenging since these organisms can be highly resistant to antimicrobial agents. Clinical illnesses associated with Acinetobacter include pneumonia, meningitis, peritonitis, endocarditis and infections of the urinary tract and skin [1]. Acinetobacter bacteremia represents a serious and ever increasing problem because of the high associated morbidity and mortality.