Faculty Bibliography

BACKGROUND:The Lung Allocation Score (LAS) significantly improved outcomes and waitlist mortality in lung transplantation. However, mortality remains high for the sickest waitlist candidates despite additional changes to allocation distance. Regulatory considerations of overhauling the current lung allocation system has met significant resistance, and would require years to implement. This study evaluates if a modest change to the current system by prioritization of only high-LAS lung transplant candidates would result in lowered waitlist mortality. METHODS:The Thoracic Simulated Allocation Model was used to evaluate all lung transplant candidates and donor lungs recovered between July 1, 2009 and June 30, 2011. Current lung allocation rules (initial offer within 250 nautical-mile radius for ABO-identical then compatible offers) were run. Allocation was then changed for only patients with an LAS≥50 (high-LAS) to be prioritized within a 500 nautical-mile radius with no stratification between ABO-identical and compatible offers. Ten iterations of each model were run. Primary endpoints were waitlist mortality and post-transplant 1-year survival. RESULTS:6,538 waitlist candidates and transplant recipients were evaluated per iteration, for a total of 130,760 simulated patients. Compared with current allocation, the adjusted model had a 23.3% decrease in waitlist mortality. Post-transplant 1-year survival was minimally affected. CONCLUSIONS:Without overhauling the entire system, simple prioritization changes to the allocation system for high-LAS candidates may lead to decreased waitlist mortality and increased organ utilization. Importantly, these changes do not appear to lead to clinically significant changes in post-transplant 1-year survival.

We conducted a retrospective review of thoracic transplant recipients (22 heart and 16 lung transplant recipients) prospectively enrolled in a single-center observational study of HCV NAT+ organ transplantation in HCV NAT- recipients. All recipients were treated with 8 weeks of glecaprevir-pibrentasvir (GP) for HCV viremia in addition to standard triple immunosuppression post-transplant. Thoracic transplant recipients of HCV NAT- organs were used as a control (24 heart and 22 lung transplant recipients). Our primary outcome was to assess the effect of GP on tacrolimus dose requirements. Secondary objectives included assessing drug interactions with common post-transplant medications, adverse effects, and the need to hold or discontinue GP therapy. The median tacrolimus concentration-to-dose (CDR) in the cohort was 184 (99-260) during GP therapy and 154 (78-304) over the first month after GP (p=0.79). Trends in median tacrolimus CDR were similar on a per-week basis and per-patient basis. In three instances, concomitant posaconazole and GP led to hyperbilirubinemia and interruption of posaconazole. GP therapy was held in one heart transplant recipient, and discontinued in another, due to unresolving hyperbilirubinemia. Utilization of GP to treat HCV viremia post-thoracic transplant is feasible and safe, but requires modifications to post-transplant pharmacotherapy and careful monitoring for adverse effects.

BACKGROUND:The role of tracheostomy during the COVID-19 pandemic remains unknown. The goal of this consensus statement is to examine the current evidence for performing tracheostomy in patients with respiratory failure from COVID-19 and offer guidance to physicians on the preparation, timing and technique while minimizing the risk of infection to health care workers (HCW). METHODS:A panel comprised of intensivists and interventional pulmonologists from three professional societies representing 13 institutions with experience in managing COVID-19 patients across a spectrum of healthcare environments developed key clinical questions addressing specific topics on tracheostomy in COVID-19. A systematic review of the literature and an established modified Delphi consensus methodology were applied to provide a reliable evidenced based consensus statement and expert panel report. RESULTS:Eight key questions, corresponding to 14 decision points, were rated by the panel. The results were aggregated, resulting in eight main recommendations and five additional remarks intended to guide health care providers in the decision-making process pertinent to tracheostomy in patients with COVID-19 related respiratory failure. CONCLUSION/CONCLUSIONS:This panel suggests performing tracheostomy in patients expected to require prolonged mechanical ventilation. A specific timing of tracheostomy cannot be recommended. There is no evidence for routine repeat RT- PCR testing in patients with confirmed Covid-19 evaluated for tracheostomy. To reduce the risk of infection in HCW, we recommend performing the procedure using techniques that minimize aerosolization while wearing enhanced personal protective equipment (PPE). The recommendations presented in this statement may change as more experience is gained during this pandemic.

PURPOSE: Azole antifungals are commonly prescribed for fungal prophylaxis (ppx) following lung transplant, but have many side effects and drug interactions. Isavuconazole, a new broad-spectrum azole antifungal, may obviate these issues.
METHOD(S): We retrospectively reviewed all lung transplant recipients (LTR) from February 2018 through September 2019 who received either ISA or POS for fungal ppx for 3 months post-transplant. Prior to February 2019 all patients received POS for ppx. Starting February 2019, POS was replaced by ISA at standard dosing. All patients received basiliximab induction and standard triple immunosuppression post-transplant. Surveillance bronchoscopies were performed at 1, 3, 6, and 12 months post-transplant.
RESULT(S): In total, we reviewed 24 LTR who received ISA and 29 who received POS. Baseline characteristics were similar between groups. Median duration of follow-up was significantly shorter for the ISA group (137 vs. 340 days, p<0.01). Breakthrough fungal infections occurred in 3 (13%) and 2 (7%) patients in the ISA and POS groups, respectively (p=0.65). All ISA patients developed oropharyngeal candidiasis; in the POS group there was one each of candida empyema and mold colonization. Post-ppx fungal infections occurred in 1 (4%) and 5 (17%) patients in the ISA and POS groups, respectively (p=0.20). All of these were mold colonization except for one case of oropharyngeal candidiasis. There was no difference between fungal-infection free survival based on Kaplan-Meier analysis (p=0.69). POS was held in two cases and discontinued in 1 patient due to a drug interaction causing hepatotoxicity compared to zero patients receiving ISA (p=0.24).
CONCLUSION(S): Breakthrough fungal infections were similar between LTR receiving ISA or POS for fungal ppx. Longer follow-up of ISA patients is needed for definitive comparison of long-term infection risk. POS was discontinued in more patients due to drug interactions. ISA is a reasonable choice for primary fungal ppx in LTR.
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PURPOSE: Adequate pain control is essential following lung transplantation to reduce patient stress and minimize perioperative complications. Enhanced recovery after surgery (ERAS) protocols have demonstrated improvements in patient experience and reduced length of stay. However, the implementation of these protocols has not yet extended to the lung transplant population.
METHOD(S): We retrospectively reviewed all lung transplant recipients (LTR) at our institution from February 2018 to August 2019. An opioid-sparing, multimodal pain regimen was implemented that included preemptive analgesia with gabapentin and acetaminophen (APAP) pre-transplant; liposomal bupivacaine intercostal nerve block (INB) in the operating room; and a combination of APAP, gabapentin, and methocarbamol post-op with opioids given as indicated. Serratus anterior plane block was used for refractory pain.
RESULT(S): In total, we reviewed 48 LTR. The mean LAS was 43.74 and 21% were on mechanical ventilation or ECMO pre-transplant. Frequency of protocol adherence for each agent was as follows: liposomal bupivacaine INB (71%), APAP (100%), gabapentin (98%), methocarbamol (27%), and ketorolac (33%). Seven patients (15%) required a serratus plane block for refractory pain. Pain scores peaked at a median of 5 on postoperative day (POD) 1 and declined to a median of 3 by POD 3. By POD 4 only 54% of patients were still receiving opioids at a median of 15 mg oral morphine equivalents per day (IQR, 0-59). Only 3 patients were discharged on opioids and they were all on opioids pre-transplant. The median duration of mechanical ventilation was 1 day (IQR, 0.64-1.69) and 81% were extubated before 48 hours. The median hospital length of stay was 8 days (IQR, 6-15) and 30-day mortality was 0%.
CONCLUSION(S): Enhanced recovery and opioid-sparing pain protocols are feasible in LTR leading to minimal opioid use and acceptable pain scores. Outcomes with ERAS protocols should be compared to standard-of-care postoperative management.
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PURPOSE: We hypothesize that home monitoring and telehealth utilizing data from a mobile healthcare application in conjunction with laboratory values and chest imaging, can replace an outpatient appointment.
METHOD(S): Our study is comprised of patients who have received a single or bilateral lung transplant or a heart/lung transplant.Before our patients are discharged from their inpatient stay after Transplantation, the application for home monitoring is installed on their smart phone. This application was specifically designed for Lung Transplant Patients. A blood pressure cuff and spirometer are provided and linked to their mobile device using Bluetooth. A weighing scale is also provided which uses a cellular connection to a secure cloud relaying data to the patient's phone and to EPIC. Additional data including (e.g. temperature, pulse oximetry) are manually entered into the application. Physical fitness (steps) is also monitored. The team who created the application enabled the data to flow from the application to our electronic medical record. Alerts are set for each piece of data and any abnormal value is sent to our team's EPIC in-basket for further action.Patients who are compliant with their home monitoring are offered telehealth. Patients are sent for laboratory testing and imaging the week of the appointment close to their home.
RESULT(S): As of October 1, 2019, we have enrolled fifty patients in our home monitoring program. Fourteen patients are now one - year post transplant. Twelve of these patients are compliant with home monitoring. Eight of them have had telehealth visits throughout the year with five receiving the majority of their care utilizing home monitoring and telehealth. These visits occur bimonthly for the first three months after transplant and then monthly for the first year.
CONCLUSION(S): Home monitoring and telehealth visits can replace outpatient visits in the first year following lung transplantation. Patients find the devices easy to use and are satisfied with the care they receive during their telehealth visits. Additionally, telehealth improves patient quality of life by reducing visits to the medical center and avoiding additional costs such as parking and time off work. It also limits pathogen exposure. Long term use may enable early detection of rejection or infection.
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PURPOSE: Thoracic organ transplantation from Hepatitis C (HCV) viremic donors is a promising strategy due to curative therapies for HCV. Currently, there is no consensus on the best time to initiate HCV therapy relative to time of transplantation. We assessed the difference in magnitude of viremia and time to clearance in recipients of heart (HT) and lung (LT) transplant, based on timing of starting antiviral HCV therapy.
METHOD(S): From January 2018 to October 2019, 42 patients received thoracic organs from viremic donors. All recipients were treated with Mavyret (glecaprevir/pibrentasvir) for 8 weeks. HT recipients received therapy at the time of detectable viremia, while LT recipients were preemptively treated within 3 days post-transplant. HCV viral load was monitored by RT-PCR.
RESULT(S): 23 patients received HT (mean age 59 +/- 9 years) and 19 patients received LT (mean age 60 +/- 9 years). HCV serologic testing was performed in HT recipients at a mean of 7 +/- 1 days and in LT recipients at a mean of 4 +/- 3 days post-transplant. At the time of testing, all HT and 14 LT patients had detectable viremia. Five LT patients never developed viremia. The mean viral load f HT was 4.5 logIU/mL and for LT was 1.6 logIU/ml. Viremia clearance was obtained at a mean of 28 +/- 13 days in HT and 21+/-11 days in LT recipients (p=0.13) (Fig). The mean time to HCV antibody (AB) clearance was 130 +/- 145 days in HT and 225 +/- 103 days in LT recipients (p=0.058). There was no correlation between the 2 groups in either the duration of viremia or HCV AB clearance.
CONCLUSION(S): Our study suggests that the magnitude and conversion to detectable viremia depends on the time of initiation of HCV therapy relative to time of transplant with complete conversion to HCV viremia in the HT group. Interestingly, there was no significance in time to viremia or HCV AB clearance between the two groups. This may be an organ specific response, but larger sample size studies need to be conducted to define the optimal time of starting HCV therapy.
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BACKGROUND:COVID-19 is a worldwide pandemic, with many patients requiring prolonged mechanical ventilation. Tracheostomy is not recommended by current guidelines as it is considered a super-spreading event due to aerosolization that unduly risks healthcare workers. METHODS:Patients with severe COVID-19 that were on mechanical ventilation ≥ 5 days were evaluated for percutaneous dilational tracheostomy. We developed a novel percutaneous tracheostomy technique that placed the bronchoscope alongside the endotracheal tube, not inside it. This improved visualization during the procedure and continued standard mechanical ventilation after positioning the inflated endotracheal tube cuff in the distal trachea. This technique offers a significant mitigation for the risk of virus aerosolization during the procedure. RESULTS:From March 10 to April 15, 2020, 270 patients with COVID-19 required invasive mechanical ventilation at New York University Langone Health Manhattan's campus of which 98 patients underwent percutaneous dilational tracheostomy. The mean time from intubation to the procedure was 10.6 days (SD ±5 days). Currently, thirty-two (33%) patients do not require mechanical ventilatory support, 19 (19%) have their tracheostomy tube downsized and 8 (8%) were decannulated. Forty (41%) patients remain on full ventilator support, while 19 (19%) are weaning from mechanical ventilation. Seven (7%) died as result of respiratory and multiorgan failure. Tracheostomy related bleeding was the most common complication (5 patients). None of health care providers have developed symptoms or tested positive for COVID-19. CONCLUSIONS:Our percutaneous tracheostomy technique appears to be safe and effective for COVID-19 patients and safe for healthcare workers.

Implementing uncontrolled donation after circulatory determination of death (uDCDD) in the United States could markedly improve supply of donor lungs for patients in need of transplants. Evidence from U.S. pilot programs suggests families support uDCDD, but only if they are asked permission for using invasive organ preservation procedures prior to initiation. However, non-invasive strategies that confine oxygenation to lungs may be applicable to the overwhelming majority of potential uDCDD donors that have airway devices in place as part of standard resuscitation. We propose an ethical framework for lung uDCDD by: (1) initiating post mortem preservation without requiring prior permission to protect the opportunity for donation until an authorized party can be found; (2) using non-invasive strategies that confine oxygenation to lungs; and (3) maintaining strict separation between the healthcare team and the organ preservation team. Attempting uDCDD in this way has great potential to obtain more transplantable lungs while respecting donor autonomy and family wishes, securing public support, and enabling authorized persons to affirm or cease preservation decisions without requiring evidence of prior organ donation intent. It ensures prioritization of life-saving, the opportunity to allow willing donors to donate, and respect for bodily integrity while adhering to current ethical norms.