Lung donor bronchoalveolar lavage positivity: Incidence, risk factors, and lung transplant recipients' outcome.

BACKGROUND: Inconsistent data exists regarding the risk factors for bronchoalveolar lavage (BAL) positivity in lung donors, the incidence of donor-derived infections (DDI), and the effect of BAL positivity on lung transplant (LuTx) recipients' outcome. METHODS: A retrospective analysis was conducted on consecutive LuTx at a single center from January 2016 to December 2022. Donors' data, including characteristics, graft function and BAL samples were collected pre-procurement. Recipients underwent BAL before LuTx and about the 3rd, 7th and 14th day after LuTx. A DDI was defined as BAL positivity (bacterial growth ≥104 colony forming units) for identical bacterial species between donor and recipient. Recipients' pre-operative characteristics, intra-operative management, and post-operative outcomes were assessed. Two recipient cohorts were identified based on lung colonization status before undergoing LuTx. RESULTS: Out of 188 LuTx procedures performed, 169 were analyzed. Thirty-six percent of donors' BAL tested positive. Donors' characteristics and graft function at procurement were not associated with BAL positivity. Fourteen DDI were detected accounting for 23% of recipients receiving a graft with a positive BAL. Only among uncolonized recipients, receiving a graft with positive BAL is associated with higher likelihood of requiring invasive ventilation at 72 hours after LuTx on higher positive end-expiratory pressure levels having lower PaO2/FiO2, prolonged duration of mechanical ventilation and longer ICU stay. No difference in hospital length of stay was observed. CONCLUSIONS: Receiving a graft with a positive BAL, which is poorly predicted by donors' characteristics, carries the risk of developing a DDI and is associated to a worse early graft function among uncolonized recipients.

Telemonitoring: An opportunity in cystic fibrosis lung transplant recipients.

Introduction: Telemedicine has been successfully employed in a wide range of conditions, such as such as chronic lung disease and COVID-19. This study evaluate the role of telemonitoring for the early diagnosis of acute lung allograft dysfunction in cystic fibrosis adults who underwent lung transplant (LuTx). Quality of life and functional level achieved during a 12 months follow up were assessed. Methods: Patients were randomized into two groups; control group received traditional hospital-based follow-up, whereas patients in the intervention group received, on top of standard care, a telemonitoring device, with a pulse oximeter and a spirometer integrated. Telemonitoring data were digitally transmitted to our centre. Results: Sixteen patients were enrolled in each group. No statistically significant difference was found between the two groups in terms of incidence of allograft dysfunction, time from onset of symptoms to diagnosis and time of occurrence from LuTx. Moreover, both groups achieved similar quality of life and functional level. With reference to the telemonitoring group: 1) hospital reported data were consistent with those being remotely registered; 2) adherence to telemonitoring decreased during the follow up; 3) the majority of patients reported a high degree of satisfaction. Conclusion: The COVID19 pandemic highlighted the necessity to investigate alternative practices to treat chronically ill individuals. Telemonitoring is a valuable tool to improve quality care to LuTx recipients.

Hemodynamic failure and graft dysfunction after lung transplant: A possible clinical continuum with immediate and long-term consequences.

INTRODUCTION: The postoperative hemodynamic management after lung transplant (LUTX) is guided by limited evidence. We aimed to describe and evaluate risk factors and outcomes of postoperative vasoactive support of LUTX recipients. METHODS: In a single-center retrospective analysis of consecutive adult LUTX, two cohorts were identified: (1) patients needing prolonged vasoactive support (>12 h from ICU admission) (VASO+); (2) or not (VASO-). Postoperative hemodynamic characteristics were thoroughly analyzed. Risk factors and outcomes of VASO+ versus VASO- cohorts were assessed by multivariate logistic regression and propensity score matching. RESULTS: One hundred and thirty-eight patients were included (86 (62%) VASO+ versus 52 (38%) VASO-). Vasopressors (epinephrine, norepinephrine, dopamine) were used in the first postoperative days (vasoactive inotropic score at 12 h: 6 [4-12]), while inodilators (dobutamine, levosimendan) later. Length of vasoactive support was 3 [2-4] days. Independent predictors of vasoactive use were: LUTX indication different from cystic fibrosis (p = .003), higher Oto score (p = .020), longer cold ischemia time (p = .031), but not preoperative cardiac catheterization. VASO+ patients showed concomitant hemodynamic and graft impairment, with longer mechanical ventilation (p = .010), higher primary graft dysfunction (PGD) grade at 72 h (PGD grade > 0 65% vs. 31%, p = .004, OR 4.2 [1.54-11.2]), longer ICU (p < .001) and hospital stay (p = .013). Levosimendan as a second-line inodilator appeared safe. CONCLUSIONS: Vasoactive support is frequently necessary after LUTX, especially in recipients of grafts of lesser quality. Postoperative hemodynamic dysfunction requiring vasopressor support and graft dysfunction may represent a clinical continuum with immediate and long-term consequences. Further studies may elucidate if this represents a possible treatable condition.

Hyperammonemia Syndrome After Lung Transplantation: A Double-Hit Fatal Syndrome. A Case Report.

Hyperammonemia after lung transplantation is a rare but potentially fatal condition. A 59-year-old male patient affected by pulmonary fibrosis underwent an uncomplicated bilateral lung transplant. Fourteen days after the procedure, the patient developed severe encephalopathy caused by elevated serum ammonia levels. Ureaplasma parvum and Mycoplasma hominis were found on bronchial aspirate and urinary samples as well as on pharyngeal and rectal swabs. Despite the initiation of multimodal therapy, brain damage due to hyperosmolarity was so extensive to evolve into brain death. The autopsy revealed glutamine synthetase hypo-expression in the hepatic tissue. The pathophysiology of hyperammonemia syndrome in lung transplant recipients remains unclear. Previous studies have described the presence of disorders of glutamine synthetase, while others considered the infection with urea-splitting microorganisms as a cause of hyperammonemia syndrome. Our report describes the case of a patient who developed hyperammonemia after a lung transplant in which both the aforementioned etiologies were documented. A high level of clinical suspicion for hyperammonemia syndrome should be maintained in lung transplant recipients. Timely recognition and treatment are critical to prevent the potentially dreadful evolution of this severe complication.

Bone Disease in Long-Term Lung Transplant Survivors.

BACKGROUND: During the first two years after lung transplantation (LTx), the incidence of fragility fractures (FX) is estimated to be 15-50% and it is lower in patients with cystic fibrosis (CF) as compared with other end-stage lung diseases (nCF). The aim of our study is to compare the skeletal outcomes, after the first 2 years post-LTx, in long-term survivors with CF and nCF. MATERIALS AND METHODS: We evaluated the FX rate, the changes in bone mineral density (BMD) and trabecular bone score (TBS) in 68 patients (38 CF and 30 nCF) who underwent LTx in our center and with a follow-up after LTx longer than 5 years (7.3 ± 2.0 years). RESULTS: After the second year post-LTx: (i) the FX rate was lower than during the first two years post-LTx (4.4 vs. 20.6%, p = 0.004), with no difference between CF and nCF patients (5.3 vs. 3.3%, p = 0.589); (ii) BMD at lumbar spine, femoral neck and total hip remained stable (-1.6 ± 1.0 vs. -1.4 ± 1.1, p = 0.431, -1.8 ± 0.9 vs. -1.9 ± 0.9, p = 0.683, -1.5 ± 0.9 vs. -1.4 ± 0.9, p = 0.678, respectively) as well as TBS (1.200 ± 0.124 vs. 1.199 ± 0.205, p = 0.166). CONCLUSIONS: After the second year post-LTx, the skeletal complications become less frequent and have similar incidence in patients with CF and nCF.

Lung Transplantation From Controlled and Uncontrolled Donation After Circulatory Death (DCD) Donors With Long Ischemic Times Managed by Simple Normothermic Ventilation and Ex-Vivo Lung Perfusion Assessment.

Donation after cardiac death (DCD) donors are still subject of studies. In this prospective cohort trial, we compared outcomes after lung transplantation (LT) of subjects receiving lungs from DCD donors with those of subjects receiving lungs from donation after brain death (DBD) donors (ClinicalTrial.gov: NCT02061462). Lungs from DCD donors were preserved in-vivo through normothermic ventilation, as per our protocol. We enrolled candidates for bilateral LT ≥14 years. Candidates for multi-organ or re-LT, donors aged ≥65 years, DCD category I or IV donors were excluded. We recorded clinical data on donors and recipients. Primary endpoint was 30-day mortality. Secondary endpoints were: duration of mechanical ventilation (MV), intensive care unit (ICU) length of stay, severe primary graft dysfunction (PGD3) and chronic lung allograft dysfunction (CLAD). 121 patients (110 DBD Group, 11 DCD Group) were enrolled. 30-day mortality and CLAD prevalence were nil in the DCD Group. DCD Group patients required longer MV (DCD Group: 2 days, DBD Group: 1 day, p = 0.011). ICU length of stay and PGD3 rate were higher in DCD Group but did not significantly differ. LT with DCD grafts procured with our protocols appears safe, despite prolonged ischemia times.

Acquired atresia of the external auditory canal and canaloplasty with Thiersch graft reconstruction: Outcomes and complications.

Acquired atresia of the external auditory canal (EAC) is a rare disease characterized by otorrhea and progressive hearing loss. Clinically, it is differentiated into two stages: the wet stage and the dry stage. The dry stage does not respond to pharmacological treatment and has to be treated surgically. One surgical option is canaloplasty of the EAC with Thiersch graft reconstruction. This study aimed to report the follow-up outcomes (otomicroscopic signs and pure tone audiometry [PTA]) in patients with acquired atresia treated with this technique. Eighteen adult patients surgically treated for acquired atresia of the EAC between 2010 and 2020 were enrolled. All underwent canaloplasty with Thiersch graft reconstruction by one senior surgeon. Otomicroscopy and PTA results were evaluated before and after surgery. Postsurgical follow-up was performed at 1-3-6-12 months and then annually. Presurgical otomicroscopic examination revealed stenosis that occluded more than 75% of the EAC in all patients, and preoperative PTA showed conductive hearing loss in 89% of patients. However, postsurgical otomicroscopic examination showed that 94% of patients had a normal EAC diameter after one year, and only one patient had anterior blunting and recurrent atresia. In addition, postsurgical PTA evidenced a normal range in 89% of patients after one year. In conclusion, acquired atresia of the EAC is a troublesome disease usually associated with hearing loss. Therefore, treatment is chosen to resolve its symptoms. The results demonstrate evidence that canaloplasty with Thirsch graft may be a suitable surgical method considering the lower incidence of recurrence and the excellent hearing outcomes.

Isolated First Branchial Cleft Anomalies of the External Auditory Canal.

BACKGROUND Branchial cleft anomalies are congenital aberrations of the first to fourth pharyngeal pouches. First branchial cleft anomalies are classified into 2 subtypes according to anatomical and histological features. Their diagnosis can be difficult and depends on radiological and histological findings. In contrast, the required treatment is surgical removal, owing to the high risk of infection or malignancy. This case report introduces a first branchial cleft anomaly in an older woman with exclusive involvement of the external auditory canal (EAC). CASE REPORT This case report introduces a first branchial cleft anomaly in an 82-year-old woman with exclusive involvement of the EAC. She reported a history of mixed moderate hypoacusis and recurrent otitis media in the last year, without facial nerve involvement. Computed tomography and magnetic resonance imaging were performed to plan surgical treatment, which consisted of canaloplasty and Thiersch grafting. The histopathological examination on operative findings revealed a cystic lesion that was lined by cylindrical epithelium adjacent to the squamous cells, compatible with a diagnosis of first branchial arch malformative residues. CONCLUSIONS This is the unique case of first branchial cleft anomalies reported in an adult patient that exclusively involved the EAC. The onset of the disease was atypical, and surgery with the total removal of the lesion was the only possible treatment. Histopathology results revealed cylindric epithelium not represented in the EAC, compatible with first branchial arch malformative residues. This rare condition is a potential diagnostic option that should be considered in the differential diagnosis of cysts of the EAC.

Lung transplantation for interstitial lung disease in idiopathic inflammatory myositis: A cohort study.

In patients with interstitial lung disease (ILD) complicating classical or amyopathic idiopathic inflammatory myopathy (IIM), lung transplantation outcomes might be affected by the disease and treatments. Here, our objective was to assess survival and prognostic factors in lung transplant recipients with IIM-ILD. We retrospectively reviewed data for 64 patients who underwent lung transplantation between 2009 and 2021 at 19 European centers. Patient survival was the primary outcome. At transplantation, the median age was 53 [46-59] years, 35 (55%) patients were male, 31 (48%) had classical IIM, 25 (39%) had rapidly progressive ILD, and 21 (33%) were in a high-priority transplant allocation program. Survival rates after 1, 3, and 5 years were 78%, 73%, and 70%, respectively. During follow-up (median, 33 [7-63] months), 23% of patients developed chronic lung allograft dysfunction. Compared to amyopathic IIM, classical IIM was characterized by longer disease duration, higher-intensity immunosuppression before transplantation, and significantly worse posttransplantation survival. Five (8%) patients had a clinical IIM relapse, with mild manifestations. No patient experienced ILD recurrence in the allograft. Posttransplantation survival in IIM-ILD was similar to that in international all-cause-transplantation registries. The main factor associated with worse survival was a history of muscle involvement (classical IIM). In lung transplant recipients with idiopathic inflammatory myopathy, survival was similar to that in all-cause transplantation and was worse in patients with muscle involvement compared to those with the amyopathic disease.

Thiersch graft follow-up with narrow band imaging for acquired atresia of the external auditory canal: Canaloplasty with Thiersch graft versus vascularization evaluated with narrow band imaging.

Acquired atresia of the external ear canal is a narrowing of the external ear canal (EAC) that appears obstructed by fibrous tissue or bone tissue. Acquired atresia has two different phases: wet and dry stage. Computed tomography (CT) scan may show a scan where soft tissue fills EAC. Treatment may be medical and/or surgical. The surgical treatment of choice is represented by canaloplasty with a skin-free flap. To our knowledge, no article has reported data on the analysis of vascularization of acquired atresia of the external ear canal and vascularization of skin flap during follow-up with narrow-band imaging. This study evaluated patients suffering from acquired atresia of the external auditory duct, treated surgically in our Department of Organi di Senso of Sapienza University, from 2017 to 2020. All patients underwent: anamnestic collection, physical examination, CT. Preoperative and postoperative otoendoscopic evaluation (1,3,6 and12 months) was performed with both cold white light endoscopic vision (CWL) and narrowband imaging (NBI). 17 patients were enrolled in the study. Preoperative otoendoscopic examination of WL showed stenosis with a diameter <75% and a tympanic membrane not viewable in all patients. At 12 months of follow-up, 94% of patients had no recurrence of external ear canal stenosis. 88% of patients had normal NBI light vascularization. Our study evaluated how NBI can be a superior method, compared to CWL, to assess the state of the flap and can be relevant in the decision-making process of a re-intervention.

Labyrinthine Fistula in Cholesteatoma Patients: Outcomes of Partial Labyrinthectomy With "Underwater Technique" to Preserve Hearing.

Labyrinthine fistula (LF) is one of the most important complications of cholesteatoma and is defined as an abnormal communication between the inner and the middle ear. This study aims to describe our experience with the partial labyrinthectomy evaluating the post-operative hearing results. Twenty-one patients who presented labyrinthine fistula in the semicircular canals were included in the present study. Hearing impairment was present in 48% of patients (10/21). A pre-operative assessment using the Gardner-Robertson hearing classification showed the following: 52%, Class I; and 48%, Class II. A post-surgical Gardner-Robertson hearing classification evidenced the following: 43%, Class I; and 57%, Class II. The presence of LF is usually considered a negative prognostic factor for hearing preservation. The key point of partial labyrinthectomy surgery is the preservation of structures, keeping them wet with Ringer's solution throughout the procedures, and not performing suction that is close to the opened LF. The bony labyrinth is drilled underwater without suction, removing the entire cholesteatoma matrix and quickly plugging the site before and after the LF. This faster plugging of the labyrinth makes it possible to preserve the peri-lymph and the endo-lymph fluid and the hearing function. This study showed that a partial labyrinthectomy is useful for maintaining serviceable hearing in patients with LF.

Evaluation of Vestibular Function in Patients Affected by Obstructive Sleep Apnea Performing Functional Head Impulse Test (fHIT).

Purpose: Obstructive sleep apnoea (OSA) is a common disease with significantly related complications. Since a connection between the vestibular nucleus and sleep regulator pathways has been demonstrated, vestibular evaluation in OSA patients was partially studied and none used functional head impulse test (fHIT) for this purpose. This paper aimed at evaluating the vestibular function in patients affected by OSA using fHIT, selecting patients who did not present any other related to cardiovascular, neurological, or metabolic diseases. Patients and Methods: Patients enrolled had a diagnosis of OSA by polysomnography type III and were cataloged according to American Association of Sleep Medicine criteria. Each patient underwent fHIT. Statistical significance was set at 0.05. Results: A total of 85 patients were enrolled in the study of which 50 had a diagnosis of OSA and were included in the case group, while 35 belonged to the control group. In 88.6% of subjects of the case group was evidenced a vestibular impairment with a substantial difference between the two study groups (p<0.05). Conclusion: The results show that the incidence of vestibular lesions in patients with obstructive sleep apnoea is underestimated and that fHIT can identify these lesions early.

Obstructive sleep apnoea patients vs laryngopharyngeal reflux disease: Non-invasive evaluation with NBI and pepsin detection in tears.

Obstructive sleep apnoea (OSA) and laryngopharyngeal reflux disease (LPR) are two common diseases that lower patients' quality of life. OSA is defined by cyclic events of airflow obstruction that occur during sleep, while LPR is characterized by upper airway inflammatory signs and symptoms due to the return of gastroduodenal gaseous and liquid elements. pH-metry is the gold standard in LPR diagnosis, but considering its invasiveness among other negative traits, questionnaires that catalog symptoms and signs of the disease such as Reflux Symptoms Index (RSI) and Reflux Finding Score (RFS) are preferred. Moreover, LPR can be evaluated by testing the presence of pepsin in tears, and Narrow Band Imaging (NBI) has been introduced for the early diagnosis of larynx oncological disease. This paper aims to test whether LPR is more frequent in OSA patients than in control ones, performing a non-invasive protocol composed of RSI, RFS test (with light vs. NBI techniques), followed by pepsin detection in tears. 68 LPR patients were enrolled in the study (45 with OSA and 23 without OSA). A strong linear relationship between Apnea-Hypopnea Index (AHI) and Oxygen Desaturation Index (ODI) was found, and patients who presented pepsin in tears had higher values of AHI and ODI in comparison to patients without it. Pathological RFS and NBI showed higher values of AHI and ODI in comparison to the control group. Furthermore, pathological RSI showed higher values of AHI and ODI in comparison to the control group. In conclusion, this diagnostic combined non-invasive protocol may be a good method to perform an early diagnosis of LPR.

Audiological and vestibular evaluations in vitiligo patients.

The aim of this paper was to investigate audiological abnormalities and potential vestibular injury in a sample of vitiligo subjects. Thirty-five patients with non-segmental vitiligo (NSV) were enrolled in the study. They underwent pure tonal audiometry (PTA), vestibular Fitzgerald-Hallpike caloric test, C-VEM, and O-VEMP testing.  The χ2 test and multiple regression analysis were performed. At PTA, 69% of patients presented with bilateral hearing loss, 8% monaural hearing loss, and 23% normal values. Bilateral caloric stimulations were performed and demonstrated that 14% of patients had a monolateral and 9% had a bilateral pathological response. VEMPs analysis showed that  20% of patients had no O-VEMPs response and 3% had no C-VEMPs response. Comparison between the normal values of healthy subjects and NSV patients showed an alteration of VEMPs in 44%. Multiple regression showed no statistical differences. We propose a specific diagnostic protocol employing PTA, bithermal caloric tests, C-VEMP, and O-VEMP testing to evaluate audio-vestibular damage. Our data were concordant with the anatomic-physiological melanocytic distribution and their possible degeneration linked with NSV.

PD-1 expression in transbronchial biopsies of lung transplant recipients is a possible early predictor of rejection.

Introduction: Chronic lung allograft dysfunction (CLAD) is the main cause of the reduced survival of lung transplanted (LTx) patients. The possible role of immune checkpoint molecules in establishing tolerance has been scarcely investigated in the setting of lung transplantation. Methods: We conducted a retrospective, observational pilot study on a consecutive series of transbronchial cryobiopsies (TCB) obtained from 24 patients during LTx follow-up focusing on PD-1, one of the most investigated immune checkpoint molecules. Results: Results showed that PD-1-expressing T lymphocytes were present in all TCB with a histological diagnosis of acute rejection (AR; 9/9), but not in most (11/15) of the TCB not resulting in a diagnosis of AR (p=0.0006). Notably, the presence of PD-1-expressing T lymphocytes in TCB resulted in a 10-times higher risk of developing chronic lung allograft dysfunction (CLAD), the main cause of the reduced survival of lung transplanted patients, thus being associated with a clearly worst clinical outcome. Discussion: Results of this pilot study indicate a central role of PD-1 in the development of AR and its evolution towards CLAD and suggest that the evaluation of PD-1-expressing lymphocytes in TCB could offer a prognostic advantage in monitoring the onset of AR in patients who underwent lung transplantation.

Petrous Bone Cholesteatoma: Facial and Hearing Preservation.

Objectives: Petrous bone cholesteatoma (PBC) is a rare condition of the petrous portion of the temporal bone. Treatment of choice consists of radical surgical removal, paying attention to protect the facial nerve and inner ear as far as possible. The aim of the present study was to evaluate the efficacy of modified translabyrinthine techniques in preserving hearing function and the use of the adjuvant endoscopic techniques in a group of PBC patients. Methods: This study comprised 16 cases of PBCs surgically treated in our Department. Pre- and post-operative hearing status was assessed with pure tone audiometry and speech discrimination and graded according to the Gardner- Robertson classification system. Facial function was based on the House Brackman (HB) classification. PBCs were grouped using Sanna's classification. The choice of surgical technique was based on the above findings together with preoperative evidence. Post-operative follow-up ranged from 1 to 10 years and also included Computed Tomography and Magnetic Resonance Imaging assessment. Results: PBCs were classified as follows: 37.5% infralabyrinthine; 43.75% supralabyrinthine; and 18.75% massive. Preservation of the bone conduction threshold was feasible in 62.5% of patients. For supralabyrinthine PBCs a subtotal petrosetomy was performed in all cases and hearing preservation was possible in 57% of them: an adjuvant endoscopic approach was performed in 43%. Infralabyrinthine PBCs were treated using a modified translabyrinthine approach with preservation of bone conduction in 83% of patients; an adjuvant endoscopic approach was performed in 50% cases. One patient with a massive cholesteatoma was treated by modified translabyrinthine approach, preserving a serviceable level of hearing. In all massive cases, an adjuvant endoscopic approach was performed. In 2 patients with preoperative palsy, facial nerve function showed an improvement. The follow-up period revealed evidence of limited recurrence at CT imaging in 2 patients. Conclusions: The introduction of modified surgical approaches, able to preserve the anatomical-functional structures, have shown an improvement of post-operative hearing outcomes.

Immune Checkpoints Expression in Chronic Lung Allograft Rejection.

Chronic lung allograft dysfunction (CLAD) is the main cause of poor survival and low quality of life of lung transplanted patients. Several studies have addressed the role of dendritic cells, macrophages, T cells, donor specific as well as anti-HLA antibodies, and interleukins in CLAD, but the expression and function of immune checkpoint molecules has not yet been analyzed, especially in the two CLAD subtypes: BOS (bronchiolitis obliterans syndrome) and RAS (restrictive allograft syndrome). To shed light on this topic, we conducted an observational study on eight consecutive grafts explanted from patients who received lung re-transplantation for CLAD. The expression of a panel of immune molecules (PD1/CD279, PDL1/CD274, CTLA4/CD152, CD4, CD8, hFoxp3, TIGIT, TOX, B-Cell-Specific Activator Protein) was analyzed by immunohistochemistry in these grafts and in six control lungs. Results showed that RAS compared to BOS grafts were characterized by 1) the inversion of the CD4/CD8 ratio; 2) a higher percentage of T lymphocytes expressing the PD-1, PD-L1, and CTLA4 checkpoint molecules; and 3) a significant reduction of exhausted PD-1-expressing T lymphocytes (PD-1pos/TOXpos) and of exhausted Treg (PD-1pos/FOXP3pos) T lymphocytes. Results herein, although being based on a limited number of cases, suggest a role for checkpoint molecules in the development of graft rejection and offer a possible immunological explanation for the worst prognosis of RAS. Our data, which will need to be validated in ampler cohorts of patients, raise the possibility that the evaluation of immune checkpoints during follow-up offers a prognostic advantage in monitoring the onset of rejection, and suggest that the use of compounds that modulate the function of checkpoint molecules could be evaluated in the management of chronic rejection in LTx patients.

Impact of bone-active drugs and underlying disease on bone health after lung transplantation: A longitudinal study.

INTRODUCTION: the effect of bone-active drugs on the risk of fragility fractures (Fx), bone mineral density (BMD) and trabecular bone score (TBS) changes in patients receiving lung transplantation (LTx) is largely unknown. This study assessed the bone-active drugs effect in patients undergoing LTx both with (CF) and without (nCF) cystic-fibrosis. METHODS: We evaluated incident Fx, both clinical and morphometric vertebral Fx by spinal X-ray, BMD and trabecular bone score (TBS) in 117 patients (CF=50, nCF n = 67) before and 24-months after LTx. A bone-active therapy was proposed to all LTx candidates. RESULTS: 83.8% of patients started a bone-active drug. Lumbar-spine (LS) T-score improved significantly only in treated patients (-1.4 ± 1.0 vs -2.0±1.0, p = 0.0001), whereas femur BMD and TBS remained stable in treated and not treated subjects. The rate of incident Fx was 15.3%, with no difference between treated and not treated patients. After LTx, LS T-score improved significantly only in nCF group (-1.3 ± 1.0 vs -1.8 ± 1.1, p = 0.0001), while femur remained stable in both nCF and CF groups. Patients with CF showed a significant Z-TBS increase (-3.6 ± 1.7 vs -3.0 ± 1.7, p = 0.019) and a lower Fx incidence as compared with nCF patients (4.1% vs 24.2%, p  =0.003). Incident Fx were associated with nCF diagnosis (OR 7.300, CI95% 1.385-38.461, p = 0.019) regardless of prevalent Fx, previous glucocorticoid therapy and bone-active therapy introduced at least 6 months before LTx. CONCLUSIONS: A prompt medical intervention helps in preventing BMD loss after LTx. As compared with nCF patients, CF patients show a TBS increase and a lower Fx risk after LTx.

Pulmonary volume-feedback and ventilatory pattern after bilateral lung transplantation using neurally adjusted ventilatory assist ventilation.

BACKGROUND: Bilateral lung transplantation results in pulmonary vagal denervation, which potentially alters respiratory drive, volume-feedback, and ventilatory pattern. We hypothesised that Neurally Adjusted Ventilatory Assist (NAVA) ventilation, which is driven by diaphragm electrical activity (EAdi), would reveal whether vagally mediated pulmonary-volume feedback is preserved in the early phases after bilateral lung transplantation. METHODS: We prospectively studied bilateral lung transplant recipients within 48 h of surgery. Subjects were ventilated with NAVA and randomised to receive 3 ventilatory modes (baseline NAVA, 50%, and 150% of baseline NAVA values) and 2 PEEP levels (6 and 12 cm H2O). We recorded airway pressure, flow, and EAdi. RESULTS: We studied 30 subjects (37% female; age: 37 (27-56) yr), of whom 19 (63%) had stable EAdi. The baseline NAVA level was 0.6 (0.2-1.0) cm H2O µV-1. Tripling NAVA level increased the ventilatory peak pressure over PEEP by 6.3 (1.8), 7.6 (2.4), and 8.7 (3.2) cm H2O, at 50%, 100%, and 150% of baseline NAVA level, respectively (P<0.001). EAdi peak decreased by 10.1 (9.0), 9.5 (9.4) and 8.8 µV (8.7) (P<0.001), accompanied by small increases in tidal volume, 8.3 (3.0), 8.7 (3.6), and 8.9 (3.3) ml kg-1 donor's predicted body weight at 50%, 100%, and 150% of baseline NAVA levels, respectively (P<0.001). Doubling PEEP did not affect tidal volume. CONCLUSIONS: NAVA ventilation was feasible in the majority of patients during the early postoperative period after bilateral lung transplantation. Despite surgical vagotomy distal to the bronchial anastomoses, bilateral lung transplant recipients maintained an unmodified respiratory pattern in response to variations in ventilatory assistance and PEEP. CLINICAL TRIAL REGISTRATION: NCT03367221.