Impact of Dual Thoracic Recovery from Circulatory Death Donors on Heart and Lung Transplant Outcomes.

OBJECTIVES: Concomitant heart and lung recovery can result in increased operative complexity, ischemic time, and competition for resources and anatomic territory. Dual thoracic recovery from circulatory death donors (DCD) may have additional risks that are not fully understood. We investigated the effects of dual heart and lung recovery from DCD donors on thoracic transplant outcomes. METHODS: Using the United Network for Organ Sharing database, we categorized all adult thoracic DCD transplants 2019-2023 by whether the donor heart, lung, or both (dual donors) were recovered. Heart and lung transplant outcomes were compared between dual recovery donors and heart-only or lung-only donors, respectively, using multivariable analyses. RESULTS: Of the 2,513 donors included, 42.9% were heart-only,45.0% were lung-only, and 12.0% were dual donors. Recipients of dual versus heart-only donors had similar likelihood of post-transplant dialysis (18.9% vs. 18.3%, p=0.84), likelihood of stroke (2.9% vs. 4.7%, p=0.34), and 2-year risk of mortality (aHR 1.15 [95% CI: 0.90-1.47], p=0.26), but lower likelihood of acute rejection (10.2% vs. 16.1%, p=0.04). Recipients of dual and lung-only donors had similar likelihood of pre-discharge acute rejection (7.6% vs. 8.5%, p=0.70), intubation at 72 hours (38.9% vs. 45.1%, p=0.13), and ECMO at 72 hours (13.1% vs. 18.1%, p=0.11), as well as 2-year risk of mortality (aHR 1.16 [95% CI: 0.74-1.82], p=0.52). CONCLUSIONS: Recovering both the heart and lungs from a DCD donor does not negatively impact transplant outcomes. Outcomes in this population should continue to be investigated as more data and longer-term follow up become available.

Incidence and Risk Factors for Stroke After Combined Heart-Kidney and Heart-Liver Transplantation.

OBJECTIVE: While stroke is a well-recognized complication of isolated heart transplantation, stroke in patients undergoing simultaneous heart-liver (HLT) and heart-kidney transplantation (HKT) has not been explored. This study assessed postoperative stroke incidence, risk factors, and outcomes in HLT and HKT compared with isolated heart transplant. METHODS: The United Network for Organ Sharing database was queried for adult patients undergoing HLT, HKT, and isolated heart transplants between 1994 and 2022. Patients were stratified by presence of in-hospital stroke after transplant. Post-transplant survival at 1-year was assessed using Kaplan-Meier analysis and log-rank tests. Separate multivariable logistic regression models were constructed to identify risk factors for stroke after HKT and HLT. RESULTS: Of 2326 HKT recipients, 85 experienced stroke, and of 442 HLT recipients, 19 experienced stroke. Stroke was more common after HKT and HLT than after an isolated heart transplant (3.7% vs. 4.3% vs. 2.9%, p = 0.01). One-year post-transplant survival was lower in those with stroke among both HKT recipients (64.5% vs. 88.7%, p(log-rank) < 0.001) and HLT recipients (43.8% vs. 87.4%, p(log-rank) < 0.001. Pre-transplant pVAD, prior stroke, postoperative dialysis, diabetes, prior cardiac surgery, and heart cold ischemic time were independent risk factors for stroke after HKT, after adjusting for age, sex, and need for blood transfusion on the waitlist. For HLT, postoperative dialysis was a significant risk factor. CONCLUSIONS: Stroke is more common after HKT and HLT than after isolated heart transplant, and results in poor survival. Independent risk factors for stroke include pre-transplant percutaneous VAD (HKT) and postoperative dialysis (HKT and HLT).

Utilization and outcomes of expanded criteria donors in adults with congenital heart disease.

BACKGROUND: Use of donation after circulatory death (DCD) and hepatitis C virus (HCV) positive donors in heart transplantation have increased the donor pool. Given poor waitlist outcomes in the adult congenital heart disease (ACHD) population, we investigated waitlist outcomes associated with willingness to consider DCD and HCV+ offers and post-transplant outcomes following HCV+ and DCD transplantation for these candidates. METHODS: Using the United Network for Organ Sharing database, we identified adult ACHD candidates and recipients listed or transplanted, respectively, between 01/01/2016 and 09/30/2023 for the HCV analysis and between 12/01/2019 and 09/30/2023 for the DCD analysis. Among candidates, we compared the cumulative incidence of transplant, with waitlist death/deterioration as a competing risk, by willingness to consider HCV+ and DCD offers. Among recipients of HCV+ (vs HCV-) and DCD (vs brain death [DBD]) transplants, we compared perioperative outcomes and post-transplant survival. RESULTS: Of 1,436 ACHD candidates from 01/01/2016 to 09/30/2023, 37.0% were willing to consider HCV+ heart offers. Of 886 ACHD candidates from 12/01/2019 to 09/30/2023, 15.5% were willing to consider DCD offers. On adjusted analysis, willingness to consider HCV+ offers was associated with 84% increased likelihood of transplant, and willingness to consider DCD offers was associated with 56% increased likelihood of transplant. Of 904 transplants between 01/01/2016 and 09/30/2023, 6.4% utilized HCV+ donors, and of 540 transplants between 12/01/2019 and 09/30/2023, 6.9% utilized DCD donors. Recipients of HCV+ (vs HCV-) and DCD (vs DBD) heart transplants had similar likelihood of perioperative outcomes and 1-year survival. CONCLUSIONS: ACHD candidates who were willing to consider HCV+ and DCD offers were more likely to be transplanted and had similar post-transplant outcomes compared to recipients of HCV- and DBD organs.

Outcomes of Heart Transplant Using High Donor Sequence Number Offers.

INTRODUCTION: Higher donor sequence numbers (DSNs) might spark provider concern about poor donor quality. We evaluated characteristics of high-DSN offers used for transplant and compared outcomes of high- and low-DSN transplants. MATERIALS AND METHODS: Adult isolated heart transplants between January 1, 2015, and December 31, 2022, were identified from the organ procurement and transplantation network database and stratified into high (≥42) and low (<42) DSN. Postoperative outcomes, including predischarge complications, hospital length of stay, and survival at 1 and 3 y, were evaluated using multivariable regressions. RESULTS: A total of 21,217 recipients met the inclusion criteria, with 2131 (10.0%) classified as high-DSN. Donor factors associated with greater odds of high-DSN at acceptance included older age, higher creatinine, diabetes, hypertension, and lower left ventricular ejection fraction. Recipients accepting high-DSN offers were older and more likely to be female, of blood type O, and have lower status at transplant. High- and low-DSN transplants had similar likelihood of stroke (3.2% versus 3.5%; P = 0.97), dialysis (12.3% versus 13.5%; P = 0.12), pacemaker implant (2.3% versus 2.1%; P = 0.64), had similar lengths of stay (16 [12-24] versus 16 [12-25] days, P = 0.38), and survival at 1 (91.6% versus 91.6%; aHR 0.85 [0.72-1.02], P = 0.08) and 3 y (84.2% versus 85.1%; aHR 0.91 [0.79-1.05], P = 0.21) post-transplant. CONCLUSIONS: High-DSN (≥42) was not an independent risk factor for post-transplant mortality and should not be the sole deterrent to acceptance. Accepting high-DSN organs may increase access to transplantation for lower-status candidates.

Changes in Donor Utilization and Outcomes for Patients Bridged With Durable Left Ventricular Assist Device.

We studied the impact of the 2018 heart allocation policy change on donor characteristics and posttransplant outcomes of left ventricular assist device (LVAD)-bridged heart transplant (HT) recipients. Left ventricular assist device-bridged adult HT recipients from October 2014 to October 2022 in the United Network for Organ Sharing database were categorized into old allocation policy (OAP) and new allocation policy (NAP) cohorts. Baseline characteristics, posttransplant outcomes, and subgroup analyses of unstable and stable LVAD-bridged recipients were assessed. The study included 7,384 HT recipients; 4,345 (58.8%) were transplanted in the OAP era and 3,039 (41.2%) in the NAP era. Old allocation policy recipients were most frequently status 1A at transplantation (71.1%), whereas NAP recipients were most frequently status 3 (40.0%), and status 4 (31.9%). Median donor sequence number (DSN) was higher in the NAP versus OAP era (9 vs. 3, p < 0.001). On multivariable analysis, NAP recipients had 20% higher 1 year mortality compared to OAP (adjusted hazard ratio [aHR] = 1.20 [95% confidence interval {CI}: 1.04-1.40], p = 0.01). Status 1 or 2 recipients had 28% higher 1 year mortality compared to status 1A (aHR = 1.28 [95% CI: 1.01-1.63], p = 0.04). Status 1 and 2 LVAD-supported recipients had higher mortality following the 2018 allocation change, indicating the need for closer surveillance of LVAD-bridged patients who may decompensate on the waitlist.

Debunking the July Effect in lung transplantation recipients.

Objective: The "July Effect" is a theory that the influx of trainees from July to September negatively impacts patient outcomes. We aimed to study this theoretical phenomenon in lung transplant recipients given the highly technical nature of thoracic procedures. Methods: Adult lung transplant hospitalizations were identified within the National Inpatient Sample (2005-2020). Recipients were categorized as academic Q1 (July to September) or Q2-Q4 (October to June). In-hospital mortality, operator-driven complications (pneumothorax, dehiscence including wound dehiscence, bronchial anastomosis, and others, and vocal cord/diaphragm paralysis, all 3 treated as a composite outcome), length of stay, and inflation-adjusted hospitalization charges were compared between both groups. Multivariable logistic regression was performed to assess the association between academic quarter and in-hospital mortality and operator-driven complications. The models were adjusted for recipient demographics and transplant characteristics. Subgroup analysis was performed between academic and nonacademic hospitals. Results: Of 30,788 lung transplants, 7838 occurred in Q1 and 22,950 occurred in Q2-Q4. Recipient demographic and clinical characteristics were similar between groups. Dehiscence (n = 922, 4% vs n = 236, 3%), post-transplant cardiac arrest (n = 532, 2% vs n = 113, 1%), and pulmonary embolism (n = 712, 3% vs n = 164, 2%) were more common in Q2-Q4 versus Q1 recipients (all P < .05). Other operator-driven complications, in-hospital mortality, and resource use were similar between groups (P > .05). These inferences remained unchanged in adjusted analyses and on subgroup analyses of academic versus nonacademic hospitals. Conclusions: The "July Effect" is not evident in US lung transplantation recipient outcomes during the transplant hospitalization. This suggests that current institutional monitoring systems for trainees across multiple specialties, including surgery, anesthesia, critical care, nursing, and others, are robust.

Special Considerations for Advanced Heart Failure Surgeries: Durable Left Ventricular Devices and Heart Transplantation.

Heart transplantation and durable left ventricular assist devices (LVADs) represent two definitive therapies for end-stage heart failure in the modern era. Despite technological advances, both treatment modalities continue to experience unique risks that impact surgical and perioperative decision-making. Here, we review special populations and factors that impact risk in LVAD and heart transplant surgery and examine critical decisions in the management of these patients. As both heart transplantation and the use of durable LVADs as destination therapy continue to increase, these considerations will be of increasing relevance in managing advanced heart failure and improving outcomes.

Bigger pies, bigger slices: Increased hospitalization costs for lung transplantation recipients in the non-donation service area allocation era.

OBJECTIVE: On November 24, 2017, lung transplant allocation switched from donation service area to a 250-nautical mile radius policy to improve equity in access to lung transplantation. Given the growing consideration of healthcare costs, we evaluated changes in hospitalization costs after this policy change. METHODS: Lung transplant hospitalizations were identified within the National Inpatient Sample from 2005 to 2020. Recipients were categorized as donation service area era (August 2015 to October 2017) or non-donation service area era (December 2017 to February 2020). Median total hospitalization costs (inflation adjusted) were compared by era nationally and regionally. Multivariable generalized linear regression was performed to determine if the removal of the donation service area was associated with total hospitalization costs. The model was adjusted for recipient demographics, Charlson Comorbidity Index, hospitalization region, transplant type (single, double), and use of extracorporeal membrane oxygenation, ex vivo lung perfusion, and mechanical ventilation. RESULTS: We analyzed 12,985 lung transplant recipients (median age of 61 years, 66% were male): 7070 in the donation service area era and 5915 in the non-donation service area era. Demographics were not different between recipients in both eras. Non-donation service area era recipients had greater extracorporeal membrane oxygenation use, mechanical ventilation (<24 hours), and longer length of stay than donation service area era recipients. Median total hospitalization costs for non-donation service area versus donation service area era recipients increased by $24,198 ($157,964 vs $182,162, percentage change = 15.32%, P < .001). Median costs increased in East North Central ($42,281) and Mountain ($35,521) regions (both P < .01). After adjustment, median costs for non-donation service area versus donation service area era recipients still increased ($19,168, 95% CI, 145-38,191, P = .048). CONCLUSIONS: Hospitalization costs for lung transplant hospitalizations have increased from 2015 to 2020. The transition from donation service area-based allocation to the non-donation service area system may have contributed to this increase after 2017 by increasing access to transplant for sicker recipients.

The Impact of Local Programmatic Decisions on Outcomes in Transplant-Listed Adults With Congenital Heart Disease.

BACKGROUND: We investigated variables impacting waitlist times and negative waitlist outcomes in adults with congenital heart disease (ACHD) who were waiting for orthotopic heart transplant (OHT) after the 2018 allocation change. METHODS: Adult candidates for OHT who were listed between 10/18/2018 and 12/31/2022 in the United Network for Organ Sharing database were categorized as ACHD vs non-ACHD. Waitlist time and time to upgrade for those upgraded into status 1-3 were compared by using rank-sum tests. Death/delisting for deterioration was assessed by using Fine-Gray subdistribution hazard ratios (SHRs). RESULTS: Of 15,424 OHT candidates, 589 (3.8%) were ACHD. ACHD vs non-ACHD candidates had less urgent status at initial listing (4.2% vs 4.7% listed at status 1; 17.2% vs 23.7% listed at status 2; P < 0.001), but not final listing (5.9% vs 7.6% final status 1; 35.6% vs 36.8% final status 2; P < 0.001). ACHD vs non-ACHD candidates upgraded into status 1 (65.0 vs 30.0 days; P = 0.09) and status 2 (113.0 vs 64.0 days; P = 0.003) spent longer times on the waitlist. ACHD vs non-ACHD candidates spent longer times waiting for an upgrade into status 1 (51.4 vs 17.6 days; P = 0.027) and status 2 (76.7 vs 34.7 days; P = 0.003). Once upgraded, there was no difference between groups in waitlist time to status 1 (9.7 vs 5.5 days = 0.66). ACHD vs non-ACHD candidates with a final status of 1 (20.0% vs 8.6%; SHR 2.47 [95%CI = 1.19-5.16]; P = 0.02) and 2 (8.9% vs 2.3%; SHR 3.59 [95%CI = 2.18-5.91]; P < 0.001) experienced higher rates of death and deterioration. CONCLUSIONS: ACHD candidates have longer waitlist times, have lower priority status at initial listing, wait longer for upgrades, and have higher mortality rates at the same final status as non-ACHD candidates, suggesting that they are being upgraded too late.

Outcomes following concomitant multiorgan heart transplantation from circulatory death donors: The United States experience.

BACKGROUND: Donation after circulatory death (DCD) has reemerged as a method of expanding the donor heart pool. Given the high waitlist mortality of multiorgan heart candidates, we evaluated waitlist outcomes associated with willingness to consider DCD offers and post-transplant outcomes following DCD transplant for these candidates. METHODS: We identified adult multiorgan heart candidates and recipients between January 1, 2020 and March 31, 2023 nationally. Among candidates that met inclusion criteria, we compared the cumulative incidence of transplant, with waitlist death/deterioration as a competing risk, by willingness to consider DCD offers. Among recipients of DCD versus brain death (DBD) transplants, we compared perioperative outcomes and post-transplant survival. RESULTS: Of 1,802 heart-kidney, 266 heart-liver, and 440 heart-lung candidates, 15.8%, 12.4%, and 31.1%, respectively, were willing to consider DCD offers. On adjusted analysis, willingness to consider DCD offers was associated with higher likelihood of transplant for all multiorgan heart candidates and decreased likelihood of waitlist deterioration for heart-lung candidates. Of 1,100 heart-kidney, 173 heart-liver, and 159 heart-lung recipients, 5.4%, 2.3%, and 2.5%, respectively, received DCD organs. Recipients of DCD and DBD heart-kidney transplants had a similar likelihood of perioperative outcomes and 1-year survival. All other DCD multiorgan heart recipients have survived to the last follow-up. CONCLUSIONS: Multiorgan heart candidates who were willing to consider DCD offers had favorable waitlist outcomes, and heart-kidney recipients of DCD transplants had similar post-transplant outcomes to recipients of DBD transplants. We recommend the use of DCD organs to increase the donor pool for these high-risk candidates.

Incidence, risk factors, and outcomes of postoperative stroke in combined heart-lung transplantation: A retrospective cohort study of the UNOS registry.

Stroke is a well-characterized complication of isolated heart and lung transplantation, but has not been described in combined heart-lung transplantation (HLTx). We retrospectively reviewed national U.S. data to describe the incidence, risk factors, and impact of postoperative stroke in HLTx recipients. Of 871 heart-lung recipients between 1994-2022, 35 (4.0%) experienced stroke, and the incidence increased over time, trending toward significance (p-trend = .07). After adjustment, extracorporeal membrane oxygenation (ECMO) (Adjusted odds ratio [aOR] = 2.63, 95%CI = [1.13-6.11]) and pre-transplant implantable defibrillator (aOR = 2.86, 95%CI = [1.20-6.81]) were independent risk factors for stroke. Postoperative stroke is common and is increasing in an era where organ allocation is driven by mechanical circulatory support (MCS) bridging.

Kidney Donation After Circulatory Death Using Thoracoabdominal Normothermic Regional Perfusion: The Largest Report of the United States Experience.

BACKGROUND: Thoracoabdominal normothermic regional perfusion (TA-NRP) has been increasingly used for donation after circulatory death (DCD) procurements in the United States. We present the largest report of outcomes of kidney transplants performed using DCD donor grafts perfused with TA-NRP. METHODS: Adult DCD kidney transplants between 2020 and 2022 in the United Network for Organ Sharing database were included. Donors with ≥50 min between asystole and aortic cross-clamp time in which the heart was also transplanted were considered TA-NRP donors. All other donors were considered direct recovery donors. Multivariable regressions were used to assess delayed graft function, as well as posttransplant survival and all-cause graft failure at 30, 90, and 180 d. A propensity-matched analysis of cohorts matched on donor Kidney Donor Profile Index was performed. RESULTS: Of the 16 140 total DCD kidney transplants performed during the study period, 306 (1.9%) used TA-NRP. TA-NRP donors were younger ( P < 0.001) and had lower Kidney Donor Profile Index ( P < 0.001) compared with direct recovery donors. Recipients receiving grafts recovered using TA-NRP were younger ( P < 0.001) and more likely to be blood group O ( P < 0.001). Transplants using TA-NRP had lower likelihood of delayed graft function (adjusted odds ratio 0.22 [95% confidence interval, 0.15-0.31], P < 0.001) but similar 180-d survival ( P = 0.8) and all-cause graft failure ( P = 0.3) as transplants using direct recovery grafts. These inferences were unchanged on propensity-matched analysis. CONCLUSIONS: Our results demonstrate that kidney transplants using TA-NRP DCD allografts have positive short-term mortality and graft survival outcomes, with significantly decreased rates of delayed graft function compared with direct recovery DCD grafts.

Association Between Retinal Pathology and Hearing in Older Adults.

We investigated the association between retinal microvascular changes and hearing loss based on the hypothesis that both may result from shared microvascular pathology. Data from 536 older adults from the National Health and Nutritional Examination Survey 2005 to 2006 including sociodemographic and health characteristics, pure-tone hearing thresholds, and retinal pathologies were collected and analyzed. Associations between retinal and hearing pathologies were modeled with multivariable-adjusted linear regressions. 75% of participants had hearing loss and 15% of participants had retinopathy. The association between retinopathy, microaneurysms, and blot hemorrhages with better speech-frequency pure tone average was -2.81 (95% confidence interval [CI]: -5.72 to 0.10), -4.75 (95% CI: -8.73 to -0.78), and -5.34 (95% CI: -8.68 to -2.00), respectively. The presence of retinopathy, microaneurysms, and blot hemorrhages was inversely associated with hearing loss. Further studies are needed to better understand the potential relationship between microvascular pathologies of the eye and ear.

Acoustic Noise Levels in High-field Magnetic Resonance Imaging Scanners.

7-Tesla (T) magnetic resonance imaging may allow for higher resolution images but may produce greater acoustic noise than 1.5- and 3-T scanners. We sought to characterize the intensity of acoustic noise from 7- versus 3-T scanners. A-weighted sound pressure levels from 5 types of pulse sequences used for brain and inner ear imaging in 3- and 7-T scanners were measured. Time-averaged sound level and maximum sound levels generated for each sequence were compared. Time-averaged sound levels exceeded 95 dB and reached maximums above 105 dB on the majority of 3- and 7-T scans. The mean time-averaged sound level and maximum sound level across pulse sequences were greater in 7- than 3-T (105.6 vs 91.4, P = .01; 114.0 vs. 96.5 dB, P < .01). 7- and 3-T magnetic resonance imaging scanners produce high levels of acoustic noise that exceed acceptable safety limits, emphasizing the need for active and passive noise protection.

Lower Oxygen Tension and Intracranial Hemorrhage in Veno-venous Extracorporeal Membrane Oxygenation.

INTRODUCTION AND METHODS: We examined the relationship between 24-h pre- and post-cannulation arterial oxygen tension (PaO2) and arterial carbon dioxide tension (PaCO2) and subsequent acute brain injury (ABI) in patients receiving veno-venous extracorporeal membrane oxygenation (VV-ECMO) with granular arterial blood gas (ABG) data and institutional standardized neuromonitoring. RESULTS: Eighty-nine patients underwent VV-ECMO (median age = 50, 63% male). Twenty (22%) patients experienced ABI; intracranial hemorrhage (ICH) was the most common diagnosis (n = 14, 16%). Lower post-cannulation PaO2 levels were significantly associated with ICH (66 vs. 81 mmHg, p = 0.007) and a post-cannulation PaO2 level < 70 mmHg was more frequent in these patients (71% vs. 33%, p = 0.007). PaCO2 parameters were not associated with ABI. By multivariable logistic regression, hypoxemia post-cannulation increased the odds of ICH (OR = 5.06, 95% CI:1.41-18.17; p = 0.01). CONCLUSION: In summary, lower oxygen tension in the 24-h post-cannulation was associated with ICH development. The precise roles of peri-cannulation ABG changes deserve further investigation, as they may influence the management of VV-ECMO patients.

Pacemaker Implantation following Heart Transplantation: Analysis of a Nation-Wide Database.

BACKGROUND: The 2018 United-Network-for-Organ-Sharing (UNOS) allocation-system changes resulted in greater recognition of mechanical circulatory support (MCS), leading to more heart transplantations (HTx) in patients with MCS. We aimed to investigate the effect of the new UNOS allocation system on the need for a permanent pacemaker and associated complications following HTx. METHODS: The UNOS Registry was questioned, to identify patients that received HTx in the US between 2000 and 2021. The primary objectives were to identify risk factors for the need for a pacemaker implantation following HTx. RESULTS: 49,529 HTx patients were identified, 1421 (2.9%) requiring a pacemaker post-HTx. Patients who required a pacemaker were older (53.9 ± 11.5 vs. 52.6 ± 12.8 years, p < 0.001), more frequently white (73% vs. 67%; p < 0.001) and less frequently black (18% vs. 20%; p < 0.001). In the pacemaker group, UNOS status 1A (46% vs. 41%; p < 0.001) and 1B (31% vs. 27%; p < 0.001) were more prevalent, and donor age was higher (34.4 ± 12.4 vs. 31.8 ± 11.5 years; p < 0.001). One-year survival was no different between the groups (HR: 1.08; 95% CI: 0.85, 1.37; p = 0.515). An era effect was observed (per year: OR: 0.97; 95% CI: 0.96, 0.98; p = 0.003), while ECMO pre-transplant was associated with lower risk of a pacemaker (OR: 0.41; 95% CI: 0.19, 0.86; p < 0.001). CONCLUSIONS: While associated with various patient and transplant characteristics, pacemaker implantation does not seem to impact one-year survival after HTx. The need for pacemaker implantation was lower in the more recent era and in patients who required ECMO pre-transplant, a finding explained by recent advances in perioperative care.

Genome Sequences of Gordonia Bacteriophages Obliviate, UmaThurman, and Guacamole.

We describe three newly isolated phages-Obliviate, UmaThurman, and Guacamole-that infect Gordonia terrae 3612. The three genomes are related to one another but are not closely related to other previously sequenced phages or prophages. The three phages are predicted to use integration-dependent immunity systems as described in several mycobacteriophages.