Late-Onset Exudative Pleural Effusions Without Concomitant Airway Obstruction or Lung Parenchymal Abnormalities: A Novel Presentation of Chronic Lung Allograft Dysfunction.

Restrictive allograft syndrome (RAS) is an aggressive variant of CLAD characterized by progressive restrictive ventilatory decline and persistent pleuro-parenchymal changes that can be seen on chest CT. We identified four lung transplant recipients with a progressive restrictive ventilatory defect due to lymphocyte-predominant exudative pleural effusions, but no pleuro-parenchymal abnormalities typical of RAS. Using molecular analysis, we also found increased levels of previously described immune markers of RAS, including NFkB, 20S proteasome, lipocalin, TNFα, and TGFß, within the circulating small extracellular vesicles of the remaining living lung transplant recipient. Despite the absence of lung parenchymal changes, these patients had a poor prognosis with rapid deterioration in allograft function and no response to pleural-based interventions such as thoracentesis, decortication, and pleurodesis. We hypothesize that these cases represent a distinct CLAD phenotype characterized by progressive restriction due to pleural inflammation, lymphocyte-predominant pleural effusion, resultant compressive atelectasis, and eventual respiratory failure in the absence of lung parenchymal involvement.

Evaluating the efficacy and safety of letermovir compared to valganciclovir for the prevention of human cytomegalovirus disease in adult lung transplant recipients.

BACKGROUND: Lung transplant recipients are at high risk for severe cytomegalovirus (CMV) disease. Off-label use of letermovir (LET) may avert myelotoxicity associated with valganciclovir (VGCV), but data in lung transplantation are limited. This study aims to evaluate the outcomes of LET prophylaxis among lung transplant recipients. METHODS: This retrospective, matched cohort study included lung transplant recipients who received LET for primary CMV prophylaxis following VGCV intolerance. Patients were matched 1:1 to historical VGCV controls based on age, serostatus group, and time from transplant. The primary outcome was CMV breakthrough within 1 year post-LET initiation; secondary outcomes included hematologic changes. RESULTS: A total of 124 lung transplant recipients were included per group (32% CMV mismatch, D+R-), with LET initiated a median of 9.6 months post-transplantation. One CMV breakthrough event (0.8%) was observed in the LET group versus four (3.2%) in the VGCV group (p = .370). The median (interquartile range) white blood cell (WBC) count was 3.1 (2.1-5.6) at LET initiation which increased to 5.1 (3.9-7.2) at the end of follow-up (p <.001). For VGCV controls, WBC was 4.8 (3.4-7.2) at baseline and 5.4 (3.6-7.2) at the end of follow-up; this difference was not statistically significant (p = .395). Additionally, 98.4% of LET patients experienced ≥1 leukopenia episode in the year prior to LET compared to 71.8% the year after initiation (p <.001). Similar results were observed for neutropenia (48.4% and 17.7%, p <.001). CONCLUSION: LET prophylaxis was associated with a low rate of CMV reactivation and leukopenia recovery. LET may represent a reasonable prophylaxis option for lung transplant recipients unable to tolerate VGCV.

Prior SARS-CoV-2 infection may not alter the clinical course of COVID-19 in lung transplant recipients: A single-center experience.

BACKGROUND: In the general population, prior infection with SARS-CoV-2 reduces the risk of severe COVID-19; however, studies in lung transplant recipients (LTRs) are lacking. We sought to describe the clinical course of COVID-19 recurrence and compare outcomes between the first and second episodes of COVID-19 in LTRs. METHODS: We conducted a retrospective, single-center cohort study of LTRs with COVID-19 between January 1, 2022, and September 30, 2022, during the Omicron wave. We compared the clinical course of a second episode of COVID-19 to that of the patients' own first episode and to that of LTRs who developed a first episode during the study period. RESULTS: During the study period, we identified 24 LTRs with COVID-19 recurrence and another 75 LTRs with a first episode of COVID-19. LTRs who survived the initial episode of COVID-19 had a similar disease course with recurrence, with a trend toward reduced hospitalization (10 (41.6%) vs. 4 (16.7%), p = .114). Furthermore, compared to LTRs with a primary infection during the Omicron wave, those with a reinfection had a non-statistically significant trend toward reduced hospitalizations (aOR .391, 95% CI [.115-1.321], p = .131), shorter lengths-of-stay (median, 4 vs. 9 days, p = .181), and reduced intensive care unit admissions, intubations, and COVID-19-related mortality. CONCLUSIONS: LTRs who survive the first episode of COVID-19 are likely to have a similar clinical course with recurrent episodes. Although recurrent COVID-19 may be milder, larger, well-powered studies are needed to confirm this observation. Ongoing precautions are warranted.

Remdesivir and molnupiravir had comparable efficacy in lung transplant recipients with mild-to-moderate COVID-19: a single center experience.

Introduction: Remdesivir (REM) and molnupiravir (MOL) are commonly used to treat lung transplant recipients (LTRs) with COVID-19; however, the clinical efficacy of these medications is yet to be compared. In this retrospective cohort study, we compared the clinical outcomes between LTRs with mild-to-moderate COVID-19 treated with REM and those treated with MOL. Methods and Results: Between March 2020 and August 2022, 195 LTRs developed COVID-19 at our center. After excluding 82 who presented with severe disease requiring hospitalization, the remaining 113 were included in the analysis: 54 did not receive antiviral treatment, 30 were treated with REM, and 29 were treated with MOL. Adjusted multivariable logistic regression analysis showed similar rates of hospitalization (adjusted odds ratio (aOR) 1.169, [95% confidence interval (95% CI) 0.105-12.997, p = 0.899], ICU admission (aOR 0.822, 95% CI 0.042-16.220, p = 0.898), mechanical ventilation (aOR 0.903, 95% CI 0.015-55.124, p = 0.961), and COVID-19-related mortality (aOR 0.822, 95% CI 0.042-16.220, p = 0.898) between LTRs treated with REM and those treated with MOL for mild-to-moderate COVID-19, irrespective of SARS-CoV-2 strain. Conclusion: MOL may be a suitable alternative to REM to treat LTRs with mild-to-moderate COVID-19, and the choice of antiviral therapy can be driven by practical considerations such as route of administration and drug availability.

Effect of different instrumentation techniques on students' performance and outcomes of nonsurgical root canal treatment.

OBJECTIVES: This study compared, retrospectively, the incidence of clinical errors and effects on treatment outcomes, when students were exposed to two different instrumentation techniques: a hybrid rotary technique (HYB), consisting of both hand instrumentation with hand stainless steel and Ni-Ti files plus the use of a rotary system (Vortex Blue, Dentsply Sirona), versus a full reciprocation instrumentation technique (WaveOne Gold [WOG], Dentsply Sirona). METHODS: A total of 368 endodontic cases (n = 184) in anterior and premolar teeth, completed by dental students at the University of Michigan School of Dentistry from 2013 to 2022, were used for the study. The groups were evaluated by two calibrated clinicians, observing the incidence of clinical errors: file separations, over-instrumentation, ledges and transportations. Treatment outcomes were also observed. Data were analyzed statistically by Fisher's exact test and Mann-Whitney U test (p < 0.05). RESULTS: No significant difference in file separations, ledges, and transportation was observed between the two groups. However, the WOG Group experienced significantly more over-instrumentation than HYB group, although this did not significantly affect tooth survival or periapical index (PAI). Cases with PAI scores of 5 were found to have significantly less tooth survival compared to the other PAI scores. CONCLUSIONS: It can be concluded that both techniques in our study are well suited to advancing the endodontic dental education of students and novice operators, anticipating relatively successful outcomes of tooth survival, as long as the cases selected are less severe in progression preoperatively.

Evolving impact of the COVID-19 pandemic on lung transplant recipients: A single-center experience.

BACKGROUND: Lung transplant recipients (LTRs) are at increased risk of morbidity and mortality from coronavirus disease 2019 (COVID-19); however, the disease course has changed as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants have mutated. We compared COVID-19-related clinical outcomes in LTRs at different stages of the pandemic. We also identified risk factors for developing severe COVID-19 independent of the dominant SARS-CoV-2 variant. METHODS: This single-center, retrospective cohort study of LTRs with COVID-19 used Cox regression analyses and bootstrapping to identify factors affecting COVID-19 severity. RESULTS: Between March 2020 and August 2022, 195 LTRs were diagnosed with COVID-19, almost half (89 [45.6%]) during the Omicron period. A total of 113 (58.5%) LTRs were hospitalized and 47 (24.1%) died. Age >65 years increased the risk of hospitalization and death. Although infection with the Omicron variant was associated with a lower risk of hospitalization, the median length of hospital stay (10 days, [interquartile range, 5-19]) was similar between the variants. Intensive care unit (ICU) admission and death were more common with the Delta variant but comparable between the original, Alpha, and Omicron variants. Remdesivir and molnupiravir reduced the risk of hospitalization, and monoclonal antibody therapy reduced the risk of ICU admission, intubation, and death. Vaccination and pre-exposure prophylaxis (PrEP) with tixagevimab-cilgavimab did not significantly reduce COVID-19-related ICU admission, intubation, or mortality among LTRs. CONCLUSIONS: LTRs with COVID-19 continue to have high hospitalization rates and prolonged hospital stays, despite the reduced virulence of the Omicron variant. More effective PrEP and therapeutic interventions for COVID-19 among vulnerable patient groups are needed.

Pre-exposure Prophylaxis with Tixagevimab-cilgavimab did not Reduce Severity of COVID-19 in Lung Transplant Recipients with Breakthrough Infection.

Lung transplant recipients (LTRs) have an increased risk of COVID-19-related morbidity and mortality. Tixagevimab-cilgavimab (tix-cil) is a long-acting monoclonal antibody combination granted Emergency Use Authorization approval by the US Food and Drug Administration for COVID-19 pre-exposure prophylaxis (PrEP) in immunocompromised patients. We sought to determine whether tix-cil 300-300 mg reduced the incidence and disease severity of severe acute respiratory syndrome coronavirus 2 infection in LTRs during the Omicron wave. Methods: We performed a retrospective, single-center cohort study of LTRs who had received a COVID-19 diagnosis between December 2021 and August 2022. We compared baseline characteristics and clinical outcomes after COVID-19 between LTRs who received tix-cil PrEP and those who did not. We then conducted propensity-score matching based on baseline characteristics and therapeutic interventions and compared clinical outcomes between the 2 groups. Results: Of 203 LTRs who received tix-cil PrEP and 343 who did not, 24 (11.8%) and 57 (16.6%), respectively, developed symptomatic COVID-19 (hazard ratio [HR], 0.669; 95% confidence interval [CI], 0.415-1.079; P = 0.099). The hospitalization rate of LTRs with COVID-19 during the Omicron wave trended lower in the tix-cil group than in the non-tix-cil group (20.8% versus 43.1%; HR, 0.430; 95% CI, 0.165-1.118; P = 0.083). In propensity-matched analyses, 17 LTRs who received tix-cil and 17 LTRs who did not had similar rates of hospitalization (HR, 0.468; 95% CI, 0.156-1.402; P = 0.175), intensive care unit admission (HR, 3.096; 95% CI, 0.322-29.771; P = 0.328), mechanical ventilation (HR, 1.958; 95% CI, 0.177-21.596; P = 0.583), and survival (HR, 1.015; 95% CI, 0.143-7.209; P = 0.988). COVID-19-related mortality was high in both propensity-score-matched groups (11.8%). Conclusions: Breakthrough COVID-19 was common among LTRs despite tix-cil PrEP, possibly due to reduced efficacy of monoclonal antibodies against the Omicron variant. Tix-cil PrEP may reduce the incidence of COVID-19 in LTRs, but it did not reduce disease severity during the Omicron wave.