ABSTRACT
Objective: The covid-19 pandemic has accelerated the use of direct-to-consumer offerings of at-home, mail-in kits for sperm DNA fragmentation. However, mail-in semen collection kits involve incubation in transport media and overnight shipping. DNA fragmentation can be confounded by multiple extrinsic factors such as storage temperatures, transportation media, handling conditions, time after ejaculation, and oxidative stress. The objective of this study was to validate the sperm chromatin dispersion test using at-home, mail-in sperm collection kits. To do so, we evaluated and assessed the effect of transportation media and shipping on sperm DNA integrity using a Halosperm G2 kit in normozoospermic human sperm samples. Material(s) and Method(s): We included a control group of ten healthy normozoospermic humans whose semen samples were analyzed for sperm DNA fragmentation using a Halosperm G2 kit. Fifty healthy normozoospermic human semen samples were included in the study group.The mean age of men in the entire cohort was 34.9 +/- 8 years. These samples were divided into two equal groups. The first group was directly analyzed for sperm DNA fragmentation using a Halosperm G2 kit in the lab. The second group samples were incubated for 24 hours in transportation media (TM), then these incubated semen samples were packaged. Shipping simulation was achieved by putting the semen samples in a cargo van for 5 hours, where temperatures, pressure, and handling fluctuated. The samples were then returned to the lab, where they were subsequently analyzed for sperm DNA fragmentation using a Halosperm G2 kit. To estimate the inter-observer variability in the scoring of sperm cells with fragmented DNA, 20 aliquots from 10 different frozen semen specimens of the control group were processed at our internal lab. The other 10 aliquots were shipped to an independent, third-party CLIA-certified laboratory and processed using the same Halosperm G2 kit technique. Result(s): The Sperm DNA fragmentation index was not statistically significantly different between the non-incubated freshly analyzed sperm samples (20 %, SD +/-9%) and the 24-hour incubated samples with shipping conditions (24% SD +/- 13) (p-value: 0.0549). During the external validation study, when the internal and external lab technicians scored the same samples, the sperm DNA fragmentation percentage (SDFs) were not statistically significantly different (p-value: 0.1213) correlated (r = 0.85, p = 0.0016). Conclusion(s): This study revealed that the sperm DNA fragmentation index of normozoospermic human sperm sample is not statically significant impacted by a 24-hour transport media incubation and subsequent exposure to shipments conditions. Impact Statement: Our study showed that the accuracy and validity of DNA fragmentation detection using the Halosperm G2 kit of TM-incubated and shipped human sperm samples was comparable to those of fresh samples analyzed at the lab in normozoospermic human sperm samples. Therefore, at-home mail-in kits may provide a viable testing option for DNA fragmentation index, helping to mitigate the barriers to access of affordable fertility care. Support: None. Copyright © 2022
ABSTRACT
Background: Interstitial Lung Disease (ILD) is the most common lung involvement in rheumatoid arthritis (RA) and leads to increased morbidity and mortality. Some retrospective observational studies suggest that abatacept (ABT) could be effective and safety, although there are no clinical trials and prospectively collected data are scarce. Objectives: To evaluate prospective the effectiveness and safety of ABT in patients with ILD associated RA (ILD-RA). Methods: Design and Protocol: We performed a multicenter, prospective, observational study of patients with interstitial lung disease secondary to rheumatoid arthritis (ILD-RA) receiving ABT between 2015 and 2021. The patients were assessed using high-resolution computed tomography and lung function tests at the beginning of treatment (V0), at 12 months (V12), and at the end of follow-up in 2021 (fV). The study was approved by the Ethics Committee (Code 1719-N-15). Main variable: effectiveness of ABT according to evolution of ILD at the end of follow-up: (1) improvement (ie improvement of FVC ≥10% or DLCO ≥15% and no radiological progression), (2) no progression (stabilization or improvement in FVC ≤ 10% or DLCO <15% and no radiological progression), (3) progression (worsening of FVC >10% or DLCO >15% and radiological progression) or (4) death. Other variables: clinical and analytical characteristics, treatments and safety (infections, hospitalization and mortality). Statistical analysis: Cox regression analysis to identify factors associated with worsening of ILD-RA treated with ABT. Results: Thirty-eight ILD-RA patients started ABT treatment during prospective follow-up. A total of 22/38 (57.9%) were men and the mean (SD) age was 66.1 (9.1) years. The mean (SD) evolution of ILD was 43.9 (30.0) months and the median (IQR) time with ABT was 17.0 (12.1-34.8) months. The baseline clini-cal-epidemiological characteristics and pulmonary progression of the patients are shown in Table 1. At the end of follow-up (fV) 28/38 (73.6%) had improvement/stabilization and 7/38 (18.4%) progressed and 3/38 (7.8%) of them died (COVID-19 pneumonia, respiratory infection and ILD progression, respectively). There were no signifcant differences in FVC (75.3 [8.7] vs 77.7 [14.6];p=0.775) or in FEV1 (83.9 [10.7] vs 84.7 [13.2];p=0.416) nor in the DLCO (61.0 [17.4] vs 60.7 [15.2];p=0.789) at the end of follow-up. There was a greater numberwith improvement/stabilization among the patients who were in combination with Methotrexate compared to those who were in monotherapy (83.3% vs 39.1%;p=0.046). The baseline variables that were independently associated with progression-mortality of ILD-RA in fV were: baseline FVC (OR [95% CI], 0.895 [0.805-0.996];p=0.042) and duration of ILD-RA (OR [95% CI], 1.204 [1.148-2.112;p=0.046]). Two patients discontinued ABT during follow-up due to insufficient joint and pulmonary response. Conclusion: More than half of the patients with ILD-RA treated with ABT manage to stabilize or improve their lung disease after a median follow-up of 17 months. Patients who worsen or die have lower baseline FVC values and ILD-RA with a longer evolution time.
ABSTRACT
Background: Intersticial lung disease (ILD) is a common condition in patients with systemic autoinmune diseases (SAI) that is characterized by increased morbility and mortality. Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, has posed huge challenges worldwide and previous studies suggest that ILD patients experience a more severe clinical course. Objectives: To analyze COVID-19 infection effects in patients with ILD associated systemic autoinmune disease (ILD-SAI) and to describe their vaccination status. Methods: Design We performed a multicenter, retrospective, observational study from 6 teaching hospitals in Andalusia, Spain. Study protocol We included ILD-SAI patients: rheumatoid arthritis (RA), systemic sclerosis (SS) and infam-matory myopathies (IM), assisted in reumatology consultations in 2021. Variables COVID-19 infection was the main variable that we collected and it was confrmed by a positive result on a PCR test. Secondary variables: (1) COVID-19 severity defned as hospitalization or death;(2) vaccination status;(3) temporary relationship between infection and vaccination. Other variables included: clinical, epidemiological characteristics, treatments received, type of ILD (UIP/NSIP), pulmonary function testing and high-resolution computed tomography. Statistic analysis Tw o multivariable logistic regression analysis to indentify the 'COVID-19' and 'severe COVID-19' associated factors. Results: We included 176 ILD-SAI, of whom: 105 (59.7%) had RA, 49 (27.8%) had SS and 22 (12.54%) had IM. The main baseline characteristics for the over-sall simple and te 3 subgroups are shown in Table 1. We recorded 22/179 (12.5%) SARS-CoV-2 infections, 7/22 (31.8%) of them were severe and 3/7 (42.85%) died. As to the vaccination, 163/176 (92.6%) patients received the complete dosis. Among those correctly vaccinated 18/163 (11%) had the SARS-CoV-2 infection, 4/18 (22.2%) after the vaccinated date and 14/18 (77.7%) when they still dint't have the complete vaccination. From the 13 not vaccinated patients, 4/13 (30.7%) had COVID-19. As to frequency, COVID-19 severity and vaccination, there were no difference between subgroups of CTD-ILD patients. The risk factors associated with the COVID-19 infection were the last FVC (OR [CI 95%], 0.971 [0.944-0.998];p=0.048), the vaccination (OR [CI 95%], 0.185 [0.049-0.691];p=0.012) and the Rituximab treatment(OR [CI 95%], 3.172 [1.028-6.785];p=0.045). Moreover, the only variable associated independently with the severe COVID-19 was the protective effect of vaccination (OR [CI 95%], 0.020 [0.003-0.119];p<0.001). Conclusion: A total of 12.5% ILD-SAI patients were COVID-19 infected, most of them without the complete vaccine. Rituximab and a deterioration of FVC were risk factors for the COVID-19 wehreas the vaccination was a protective factor for the mild and severe infection.