Characterization of anogenital distance and its relationship to fertility in lactating Holstein cows

peer-reviewedAnogenital distance (AGD) serves as a marker for prenatal androgenization, reproductive development, and fertility in humans and rodents. The primary objectives of this observational study in lactating dairy cows were to (1) characterize the distribution and variability of AGD, (2) determine the relationship among AGD and potential postnatal AGD determinants of age and height, and (3) evaluate the associations between AGD and pregnancy to first artificial insemination (P/AI) and cumulative pregnancy by 250 d in milk (DIM) within parity groups (first, second, and third+ parities). The secondary objective was to evaluate the association between AGD and testosterone concentrations. The AGD (mm), age (yr), and height at hip (cm) at the time of AGD determination, and aforesaid reproductive outcomes were determined in 921 Holstein cows (first, second, and third+ parity; n = 360, 256, and 305, respectively). Plasma concentrations of testosterone were determined in a subset of 93 cows. Overall, AGD had a normal distribution and high variability [mean (±standard deviation); 131.0 ± 12.2 mm], was weakly associated with cow age and height (coefficient of determination = 0.09 and 0.04, respectively), and had an inverse relationship with P/AI in first- and second-parity cows, but not in third+ parity cows. For every 1 mm increase in AGD, the odds of P/AI decreased by 3.4 and 2.4% for first- and second-parity cows, respectively. The optimal AGD threshold to predict probability of P/AI was 127.1 mm for both first- (sensitivity: 66.4; specificity: 56.6%) and second-parity cows (sensitivity: 46.0; specificity: 70.4%). Accordingly, first- and second-parity cows were categorized into either short or long AGD (≤ or >127.1 mm), and associations with reproductive outcomes were evaluated. First-parity cows with long AGD had lower P/AI (30.9 vs. 53.6%) and decreased likelihood (hazard ratio: 0.68) of pregnancy by 250 DIM than those with short AGD. Similarly, second-parity cows with long AGD had reduced P/AI (28.3 vs. 44.4%) and a tendency for decreased likelihood (hazard ratio: 0.76) of pregnancy by 250 DIM than in cows with short AGD. The association between AGD and testosterone was weak and nonsignificant. In summary, AGD in Holstein cows was normally distributed, highly variable, and weakly associated with age and height. Besides, AGD had an inverse relationship with P/AI and cumulative pregnancy by 250 DIM in first- and second-parity cows; however, such a relationship was not evident in older (third+ parity) cows.This project was financially supported in part by Growing Forward 2, a federal-provincial-territorial initiative (Research Opportunities and Innovation–Internal Initiatives Project # DA7642064). M. Gobikrushanth is a recipient of the Teagasc-University of Alberta Walsh Fellowship sponsored by Alberta Innovates Biosolutions

Characterization of anogenital distance and its relationship to fertility in lactating Holstein cows

Anogenital distance (AGD) serves as a marker for prenatal androgenization, reproductive development, and fertility in humans and rodents. The primary objectives of this observational study in lactating dairy cows were to (1) characterize the distribution and variability of AGD, (2) determine the relationship among AGD and potential postnatal AGD determinants of age and height, and (3) evaluate the associations between AGD and pregnancy to first artificial insemination (P/AI) and cumulative pregnancy by 250 d in milk (DIM) within parity groups (first, second, and third+ parities). The secondary objective was to evaluate the association between AGD and testosterone concentrations. The AGD (mm), age (yr), and height at hip (cm) at the time of AGD determination, and aforesaid reproductive outcomes were determined in 921 Holstein cows (first, second, and third+ parity; n = 360, 256, and 305, respectively). Plasma concentrations of testosterone were determined in a subset of 93 cows. Overall, AGD had a normal distribution and high variability [mean (±standard deviation); 131.0 ± 12.2 mm], was weakly associated with cow age and height (coefficient of determination = 0.09 and 0.04, respectively), and had an inverse relationship with P/AI in first- and second-parity cows, but not in third+ parity cows. For every 1 mm increase in AGD, the odds of P/AI decreased by 3.4 and 2.4% for first- and second-parity cows, respectively. The optimal AGD threshold to predict probability of P/AI was 127.1 mm for both first- (sensitivity: 66.4; specificity: 56.6%) and second-parity cows (sensitivity: 46.0; specificity: 70.4%). Accordingly, first- and second-parity cows were categorized into either short or long AGD (≤ or >127.1 mm), and associations with reproductive outcomes were evaluated. First-parity cows with long AGD had lower P/AI (30.9 vs. 53.6%) and decreased likelihood (hazard ratio: 0.68) of pregnancy by 250 DIM than those with short AGD. Similarly, second-parity cows with long AGD had reduced P/AI (28.3 vs. 44.4%) and a tendency for decreased likelihood (hazard ratio: 0.76) of pregnancy by 250 DIM than in cows with short AGD. The association between AGD and testosterone was weak and nonsignificant. In summary, AGD in Holstein cows was normally distributed, highly variable, and weakly associated with age and height. Besides, AGD had an inverse relationship with P/AI and cumulative pregnancy by 250 DIM in first- and second-parity cows; however, such a relationship was not evident in older (third+ parity) cows.This project was financially supported in part by Growing Forward 2, a federal-provincial-territorial initiative (Research Opportunities and Innovation–Internal Initiatives Project # DA7642064). M. Gobikrushanth is a recipient of the Teagasc-University of Alberta Walsh Fellowship sponsored by Alberta Innovates Biosolutions

Effect of lung recruitment and titrated Positive End-Expiratory Pressure (PEEP) vs low PEEP on mortality in patients with acute respiratory distress syndrome - A randomized clinical trial

IMPORTANCE: The effects of recruitment maneuvers and positive end-expiratory pressure (PEEP) titration on clinical outcomes in patients with acute respiratory distress syndrome (ARDS) remain uncertain. OBJECTIVE: To determine if lung recruitment associated with PEEP titration according to the best respiratory-system compliance decreases 28-day mortality of patients with moderate to severe ARDS compared with a conventional low-PEEP strategy. DESIGN, SETTING, AND PARTICIPANTS: Multicenter, randomized trial conducted at 120 intensive care units (ICUs) from 9 countries from November 17, 2011, through April 25, 2017, enrolling adults with moderate to severe ARDS. INTERVENTIONS: An experimental strategy with a lung recruitment maneuver and PEEP titration according to the best respiratory-system compliance (n = 501; experimental group) or a control strategy of low PEEP (n = 509). All patients received volume-assist control mode until weaning. MAIN OUTCOMES AND MEASURES: The primary outcome was all-cause mortality until 28 days. Secondary outcomes were length of ICU and hospital stay; ventilator-free days through day 28; pneumothorax requiring drainage within 7 days; barotrauma within 7 days; and ICU, in-hospital, and 6-month mortality. RESULTS: A total of 1010 patients (37.5% female; mean [SD] age, 50.9 [17.4] years) were enrolled and followed up. At 28 days, 277 of 501 patients (55.3%) in the experimental group and 251 of 509 patients (49.3%) in the control group had died (hazard ratio [HR], 1.20; 95% CI, 1.01 to 1.42; P = .041). Compared with the control group, the experimental group strategy increased 6-month mortality (65.3% vs 59.9%; HR, 1.18; 95% CI, 1.01 to 1.38; P = .04), decreased the number of mean ventilator-free days (5.3 vs 6.4; difference, −1.1; 95% CI, −2.1 to −0.1; P = .03), increased the risk of pneumothorax requiring drainage (3.2% vs 1.2%; difference, 2.0%; 95% CI, 0.0% to 4.0%; P = .03), and the risk of barotrauma (5.6% vs 1.6%; difference, 4.0%; 95% CI, 1.5% to 6.5%; P = .001). There were no significant differences in the length of ICU stay, length of hospital stay, ICU mortality, and in-hospital mortality. CONCLUSIONS AND RELEVANCE: In patients with moderate to severe ARDS, a strategy with lung recruitment and titrated PEEP compared with low PEEP increased 28-day all-cause mortality. These findings do not support the routine use of lung recruitment maneuver and PEEP titration in these patients. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01374022