Use of sirolimus in the treatment of lymphangioleiomyomatosis: favorable responses in patients with different extrapulmonary manifestations

OBJECTIVE:

Lymphangioleiomyomatosis (LAM) is a rare disease that is currently considered a low-grade neoplasm with metastatic potential and variable progression. Mammalian target of rapamycin (mTOR) inhibitors, such as sirolimus and everolimus, have recently become a treatment option for LAM patients, especially those with extrapulmonary manifestations. The objective of the present study was to describe a case series of four patients with LAM in Brazil who showed significant improvement, particularly in their extrapulmonary manifestations, after treatment with sirolimus (at 1-4 mg/day).

METHODS:

We describe four cases of LAM patients with different extrapulmonary manifestations who were treated with sirolimus.

RESULTS:

After treatment with sirolimus for 12 months, one patient presented resolution of severe chylothorax; one had a significant reduction in renal angiomyolipoma volume; and one showed significant regression of retroperitoneal lymphangioleiomyomas and abdominal lymph node enlargement. After treatment with sirolimus for 6 months, the remaining patient had a significant reduction in the volume of a massive retroperitoneal lymphangioleiomyoma.

CONCLUSIONS:

Our findings confirm that mTOR inhibitors are beneficial for patients with LAM, especially those with extrapulmonary manifestations, such as renal angiomyolipoma, lymphangioleiomyomas, and chylous effusions. However, certain aspects, such as the optimal dose, duration of treatment, and long-term adverse effects, have yet to be sufficiently clarified for mTOR inhibitors to be incorporated into LAM management protocols.     

Ultrasound analysis of mental artery flow in elderly patients: a case–control study

Objectives:

Mental artery flow decreases with age and may have an aetiological role in alveolar ridge atrophy. The aim of this study was to identify factors associated with alterations of mental artery flow, assessed by ultrasonography.

Methods:

This case–control study was conducted on elderly patients (aged above 60 years) at the beginning of dental treatment. Intraoral B-mode Doppler ultrasonography was used to assess mental artery flow. The cases were defined as patients with a weak/absent ultrasound signal, whereas the controls presented a strong ultrasound signal. Demographics and radiographic findings (low bone mineral density on dual-energy X-ray absorptiometry and mandibular cortical index on panoramic radiographs) were analysed as risk factors for weak/absent ultrasound signal and were calculated as adjusted odds ratios (AORs) with 95% confidence intervals (CIs) using conditional logistic regression. In addition, the Student''s t-test was used to compare the mean alveolar bone height of the analysed groups. A p-value <0.05 was considered statistically significant.

Results:

A total of 30 ultrasound examinations (12 cases and 18 controls) were analysed. A weak/absent mental artery pulse strength was significantly associated with edentulism (AOR = 3.67; 95% CI = 0.86–15.63; p = 0.046). In addition, there was a significant difference in alveolar bone height between edentulous cases and controls (p = 0.036).

Conclusions:

Within the limitations of this study, the present results indicate that edentulism is associated with diminished mental artery flow, which, in turn, affects alveolar bone height.     

Disappearance of T Cell-Mediated Rejection Despite Continued Antibody-Mediated Rejection in Late Kidney Transplant Recipients

The prevalent renal transplant population presents an opportunity to observe the adaptive changes in the alloimmune response over time, but such studies have been limited by uncertainties in the conventional biopsy diagnosis of T cell-mediated rejection (TCMR) and antibody-mediated rejection (ABMR). To circumvent these limitations, we used microarrays and conventional methods to investigate rejection in 703 unselected biopsies taken 3 days to 35 years post-transplant from North American and European centers. Using conventional methods, we diagnosed rejection in 205 biopsy specimens (28%): 67 pure TCMR, 110 pure ABMR, and 28 mixed (89 designated borderline). Using microarrays, we diagnosed rejection in 228 biopsy specimens (32%): 76 pure TCMR, 124 pure ABMR, and 28 mixed (no borderline). Molecular assessment confirmed most conventional diagnoses (agreement was 90% for TCMR and 83% for ABMR) but revealed some errors, particularly in mixed rejection, and improved prediction of failure. ABMR was strongly associated with increased graft loss, but TCMR was not. ABMR became common in biopsy specimens obtained >1 year post-transplant and continued to appear in all subsequent intervals. TCMR was common early but progressively disappeared over time. In 108 biopsy specimens obtained 10.2–35 years post-transplant, TCMR defined by molecular and conventional features was never observed. We conclude that the main cause of kidney transplant failure is ABMR, which can present even decades after transplantation. In contrast, TCMR disappears by 10 years post-transplant, implying that a state of partial adaptive tolerance emerges over time in the kidney transplant population.     

Reduced Incidence of Cytomegalovirus Infection in Kidney Transplant Recipients Receiving Everolimus and Reduced Tacrolimus Doses

This study compared the incidence of CMV infection/disease in de novo kidney transplant recipients receiving everolimus or mycophenolate and no CMV pharmacological prophylaxis. We randomized 288 patients to receive a single 3 mg/kg dose of antithymocyte globulin, tacrolimus, everolimus, and prednisone (r‐ATG/EVR, n = 85); basiliximab, tacrolimus, everolimus, and prednisone (BAS/EVR, n = 102); or basiliximab, tacrolimus, mycophenolate, and prednisone (BAS/MPS, n = 101). The primary end‐point was the incidence of first CMV infection/disease in the intention‐to‐treat population at 12 months. Patients treated with r‐ATG/EVR showed a 90% proportional reduction (4.7% vs. 37.6%, HR 0.10, 95% CI 0.037–0.29; p < 0.001), while those treated with BAS/EVR showed a 75% proportional reduction (10.8% vs. 37.6%, HR 0.25, 95% CI 0.13–0.48; p < 0.001) in the incidence of CMV infection/disease compared to BAS/MPS. There were no differences in the incidence of acute rejection (9.4 vs. 18.6 vs. 15.8%, p = 0.403), wound‐healing complications, delayed graft function, and proteinuria. Mean estimated glomerular filtration rate was lower in BAS/EVR (65.7 ± 21.8 vs. 60.6 ± 20.9 vs. 69.5 ± 21.5 ml/min, p = 0.021). In de novo kidney transplant recipients receiving no pharmacological CMV prophylaxis, reduced‐dose tacrolimus and everolimus was associated with a significant reduction in the incidence of CMV infection/disease compared to standard tacrolimus dose and mycophenolate ( ClinicalTrials.gov NCT01354301).     

How to manage inflammatory bowel disease during the COVID-19 pandemic: A guide for the practicing clinician

Managing inflammatory bowel disease (IBD) during the coronavirus disease 2019 (COVID-19) pandemic has been a challenge faced by clinicians and their patients, especially concerning whether to proceed with biologics and immunosuppressive agents in the background of a global outbreak of a highly contagious new coronavirus (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2). The knowledge about the impact of this virus on patients with IBD, although it is still scarce, is rapidly evolving. In particular, concerns surrounding medications’ impact for IBD on the risk of acquiring SARS-CoV-2 infection or developing COVID-19, and potentially exacerbate viral replication and the COVID-19 course, are a current thinking of both practicing clinicians and providers caring for patients with IBD. Managing patients with IBD infected with SARS-CoV-2 depends on both the clinical activity of the IBD and the occasional development and severity of COVID-19. In this review, we summarize the current data regarding gastrointestinal involvement by SARS-CoV-2 and pharmacologic and surgical management for IBD concerning this infection, and the COVID-19 impact on both the patient's psychological functioning and endoscopy services, and we concisely summarize the telemedicine roles during the COVID-19 pandemic.     

Effects of Mat Pilates on hip and knee isokinetic torque parameters in elderly women

This study aimed to analyze the effects of Mat Pilates on isokinetic torque of the lower limbs in elderly women. Fourteen elderly women (Age 62 ± 3 yr) participated in 12 weeks of Mat Pilates training (60-min sessions, 3 times per week). Repetitions increased every 4 weeks and the difficulty of exercises progressed from beginner to intermediate and advanced. Peak torque was assessed before (week ‐4 and week 0, considered as a control period) and after 6 and 12 weeks of a periodized Mat Pilates intervention. The results showed significant improvements (p < 0.05) in concentric and eccentric peak torque of knee flexors muscles, hip flexor and extensor muscles after 12 weeks. Mechanical work showed significant improvement (p < 0.05) for knee extensor muscles during eccentric contractions after week 12, for hip extensor muscles during concentric contractions week 12, and for flexor muscles during concentric and eccentric contractions after week 12. We conclude that the periodization of Mat Pilates induced significant improvements in multiple isokinetic torque parameters.     

Salt tolerance of rhizobial populations from contrasting environmental conditions: understanding the implications of climate change

Ecotoxicology - It is predicted that global climate change may alter environmental parameters such as rainfall distribution which in turn may alter the salinity of soils with unpredictable effects...