Prospective associations of plasma growth differentiation factor 15 with physical performance and cognitive functions in older adults

Background Growth differentiation factor 15 (GDF15) has been associated with several age-related disorders, but its associations with functional abilities in community-dwelling older adults are not well studied. Methods The study was a secondary analysis on 1096 community-dwelling older adults (aged 69 to 94 years) recruited from the Multidomain Alzheimer’s Preventive Trial. Plasma GDF15 was measured one year after participants’ enrolment. Annual data of physical performance (grip strength and short physical performance battery [SPPB]) and global cognitive functions (mini-mental state examination [MMSE] and a composite cognitive score) were measured for four years. Adjusted mixed-effects linear models were performed for cross-sectional and longitudinal association analyses. Results A higher GDF15 was cross-sectionally associated with a weaker grip strength (β = -1.1E-03, 95%CI [-2.0E-03, -1.5E-04]), a lower SPPB score (β = -3.1E-04, 95%CI [-5.4E-04, -9.0E-05]) and worse cognitive functions (β = -2.4E-04, 95%CI [-3.3E-04, -1.6E-04] for composite cognitive score; β = -4.0E-04, 95%CI [-6.4E-04, -1.6E-04] for MMSE). Participants with higher GDF15 demonstrated greater longitudinal declines in SPPB (β = -1.0E-04, 95%CI [-1.7E-04, -2.0E-05]) and composite cognitive score (β = -2.0E-05, 95%CI [-4.0E-05, -3.6E-06]). The optimal initial GDF15 cutoff values for identifying participants with minimal clinically significant decline after one year were 2189 pg/mL for SPPB (AUC: 0.580) and 2330 pg/mL for composite cognitive score (AUC: 0.587). Conclusions Plasma GDF15 is cross-sectionally and longitudinally associated with lower-limb physical performance and global cognitive function in older adults. Circulating GDF15 alone has limited capacity of discriminating older adults who will develop clinically significant functional declines.

Changes in macular thickness post uncomplicated MSICS & phacoemulsification surgery

To evaluate changes in macular thickness via-a-vis visual acuity post uncomplicated manual small incision cataract surgery (MSICS) & phacoemulsification surgery Prospective clinical study on 160 patients of uncomplicated immature senile cataract, aged 40-70yrs, patients were randomised into two groups, MSICS & phacoemulsification, by simple 1:1 randomization, who underwent uncomplicated cataract surgery with posterior chamber intraocular lens (PCIOL). Post-operatively, the patients were evaluated for best corrected visual acuity (BCVA) and changes in macular thickness by optical coherence tomography (OCT) at post-op Day 1, 7, 21, 48, and 12 weeks. Paired t-test was used for comparison across follow up. : At 12 weeks post-operative, mean logMAR BCVA was 0.01±0.02 for MSICS group and 0±0.02 for Phacoemulsification group. Macular thickness was not statistically significant (p=0.342) between MSICS group (219.19±17.88µm) and Phacoemlusification group (215.61±16.21µm), at the end of 12 weeks post-operative. Clinically significant macular oedema was not diagnosed in any of the patients at the follow-ups.: Both procedures achieved good post-operative Best Corrected visual acuity without significant differences in BCVA between both the groups at the end of 12 weeks.

Comparing Micro-Ultrasound to mpMRI in Detecting Clinically Significant Prostate Cancer

Objectives To compare the performance of micro-ultrasound (mUS) with multi-parametric magnetic resonance imaging (mpMRI) in detecting clinically significant prostate cancer. Materials and Methods Retrospective data from consecutive patients with any indication for prostate biopsy in 2 academic institutions were included. The operator, blinded to mpMRI, would first scan the prostate and annotate any mUS lesions. All mUS lesions were biopsied. Any mpMRI lesions that did not correspond to mUS lesion upon unblinding were additionally biopsied. Grade group (GG) ≥ 2 was considered clinically significant cancer. The Jeffreys interval method was used to compare performance of mUS with mpMRI with the non-inferiority limit set at −5%. Results Imaging and biopsy were performed in 82 patients with 153 lesions. mUS had similar sensitivity to mpMRI (per-lesion analysis: 78.4% versus 72.5%), but lower specificity, positive predictive value, negative predictive value, and area under the curve. Micro-ultrasound found GG ≥ 2 in 13% of cases missed by mpMRI, while mpMRI found GG ≥ 2 in 11% of cases missed by mUS. The difference 0.020 (95% CI −0.070 to 0.110) was not statistically significant (P = 0.33). Conclusion The sensitivity of mUS in detecting GG ≥ 2 disease was similar to that of mpMRI, but the specificity was lower. Further evaluation with a larger sample size and experienced operators is warranted.

Comparison of Two Different Uses of Underbody Forced-air Warming Blankets for the Prevention of Hypothermia in Patients Undergoing Arthroscopic Shoulder Surgery: a Prospective Randomized Study

Background: Forced-air warming (FAW) is an effective method of preventing inadvertent perioperative hypothermia (IPH). However, its warming effects can be influenced by the style and position of the FAW blanket. This study aimed to compare the effects of underbody FAW blankets being placed under or over patients in preventing IPH.Methods: Patients (n=100) undergoing elective arthroscopic shoulder surgery in the lateral decubitus position were randomized into either under body (UB) group or the over body (OB) group (50 per group). The core body temperature (CBT) of the patients was recorded from baseline to the end of anesthesia. The incidences of postoperative hypothermia and shivering were also collected.Results: A steady decline in the CBT was observed in both groups up to 60 minutes after the start of FAW. After 60 minutes of warming, the OB group showed a gradual increase in the CBT. However, the CBT still decreased in UB group until 75 minutes, with a low of 35.7℃ ± 0.4℃. Then the CBT increased mildly and reached 35.8℃ ± 0.4℃ at 90 minutes. After 45 minutes of warming, the CBT was significantly different (P < 0.05). The incidence of postoperative hypothermia in the UB group was significantly higher than that in the OB group (P = 0.023).Conclusions: The CBT was significantly better when the underbody FAW blanket was placed over patients compared with under the patients. However, there was not a clinically significant difference in CBT. The incidence of postoperative hypothermia was much lower in the OB group. Therefore, placing underbody FAW blankets over patients is recommended for the prevention of IPH in patients undergoing arthroscopic shoulder surgery.Trial registration: This single-center, prospective, RCT has completed the registration of the Chinese Clinical Trial Center at 13/1/2021 with the registration number ChiCTR2100042071. It was conducted from 14/1/2021 to 30/10/2021 as a single, blinded trial in Sichuan Provincial Orthopedic Hospital.

Respiratory system compliance at the same PEEP level is similar in COVID and non-COVID ARDS

Background The comparison of respiratory system compliance (Crs) between COVID and non-COVID ARDS patients has been the object of debate, but few studies have evaluated it when considering applied positive end expiratory pressure (PEEP), which is one of the known determinants of Crs itself. The aim of this study was to compare Crs taking into account the applied PEEP. Methods Two cohorts of patients were created: those with COVID-ARDS and those with non-COVID ARDS. In the whole sample the association between Crs and type of ARDS at different PEEP levels was adjusted for anthropometric and clinical variables. As secondary analyses, patients were matched for predicted functional residual capacity and the same association was assessed. Moreover, the association between Crs and type of ARDS was reassessed at predefined PEEP level of 0, 5, 10, and 15 cmH2O with a propensity score-weighted linear model. Results 367 patients were included in the study, 276 patients with COVID-ARDS and 91 with non-COVID ARDS. The association between Crs and type of ARDS was not significant in both the complete cohorts (p = 0.17) and in the matched cohorts (p = 0.92). This was true also for the propensity score weighted association at PEEP 5, 10 and 15 cmH2O, while it was statistically significant at PEEP 0 (with a median difference of 3 ml/cmH2O, which in our opinion is not clinically significant). Conclusions The compliance of the respiratory system is similar between COVID ARDS and non-COVID ARDS when calculated at the same PEEP level and while taking into account patients’ anthropometric characteristics.

Greater Trochanteric Pain Syndrome (GTPS): A clinical prospective study of treatment options

Background: There are few prospective studies evaluating the efficacy of various non-operative strategies for treatment of greater trochanter pain syndrome (GTPS). There is a diversity of available interventions and lack of clear consensus for the best modality thus far. Design: Observational prospective cohort study performed during the period of October 2017 and March 2019. Methods: The main objective was to determine if there is a difference in outcome of the Lower Extremity Functional Scale (LEFS) for subjects treated with conservative management (PT), corticosteroid injection (CSI), or percutaneous ultrasonic tenotomy (PUT). Participants were assigned based on physician treatment in a non-randomized manner to PT, a single CSI, or the PUT treatment arm. Subjects participated in outcome assessments at baseline and at 1-, 3-, 6-, and 12-months post intervention. Results: 112 individuals with unilateral GTPS were recruited for this study with 69 PT patients, 31 CSI patients, and 12 PUT patients. The adjusted mean LEFS scores averaged across all time periods remained statistically different between PT, CSI, and PUT (p = 0.0093), indicating significant difference between each treatment arm. PT group saw the greatest improvements from baseline score starting at 1 month and up to 1 year (p = .0004). CSI group did not see significant LEFS improvement until 6 months (p = 0.04) and did not maintain clinically significant improvement by 1 year. PUT group saw significant LEFS improvement at 3 months (p = 0.0001) and maintained clinically significant improvements (≥ 9 LEFS points) throughout the course of the study. Conclusion: PT patients over the study period showed the greatest improvements in LEFS scores compared to CSI and PUT patients. We believe that PT is the best indicated course of treatment for GTPS. PUT may be considered as an additional option if patients have failed other treatment modalities. CSI shows benefit at 6 months, but overall inferior to PT and PUT.

Generation and characterisation of P. falciparum parasites with a G358S mutation in the PfATP4 Na+ pump and clinically relevant levels of resistance to some PfATP4 inhibitors

Small-molecule inhibitors of PfATP4, a Plasmodium falciparum protein that is believed to pump Na+ out of the parasite while importing H+, are on track to become much-needed new antimalarial drugs. The spiroindolone cipargamin is poised to become the first PfATP4 inhibitor to reach the field, having performed strongly in Phase 1 and 2 clinical trials. Previous attempts to generate cipargamin-resistant parasites in the laboratory have yielded parasites with reduced susceptibility to the drug; however, the highest 50% inhibitory concentration reported to date is 24 nM. Here, we show that P. falciparum parasites can acquire a clinically-significant level of resistance to cipargamin that enables them to withstand micromolar concentrations of the drug. Independent experiments to generate high-level cipargamin resistance using different protocols and strains led to the same change each time - a G358S mutation in PfATP4. Parasites with this mutation showed high-level resistance not only to cipargamin, but also to the dihydroisoquinolone (+)-SJ733. However, for certain other (less clinically advanced) PfATP4-associated compounds the G358S mutation in PfATP4 conferred only moderate resistance or no resistance. The G358S mutation in PfATP4 did not affect parasite susceptibility to antimalarials that do not target PfATP4. The G358S mutation in PfATP4, and the equivalent mutation in the Toxoplasma gondii ATP4 homologue (G419S), decreased the sensitivity of the Na+-ATPase activity of ATP4 to inhibition by cipargamin and (+)-SJ733, and decreased the sensitivity of parasites expressing these ATP4 mutations to disruption of parasite Na+ regulation by cipargamin- and (+)-SJ733. The G358S mutation in PfATP4 reduced the affinity of the protein for Na+ and was associated with an increase in the parasite's resting cytosolic Na+ concentration; however, no significant defect in parasite growth rate was observed. Our findings suggest that codon 358 in pfatp4 should be monitored closely in the field as a molecular marker for cipargamin resistance, and that PfATP4 inhibitors in clinical development should be tested for their activity against PfATP4G358S parasites.