Influence of donor capnometry on renal graft evolution in uncontrolled donation after circulatory death.

AIM: To analyse the association between donor capnometry data and the short-term evolution of kidney grafts in cases of uncontrolled donation after circulatory death (uDCD). METHOD: We used an ambispective observational study design, conducted in the Community of Madrid between January and December 2019, inclusive. Patients who suffered out-of-hospital cardiac arrest (CA) with no response to advanced cardiopulmonary resuscitation (CPR) were selected as potential donors. Donor capnometry levels were measured at the start, midpoint and transfer to hospital then compared with indicators of renal graft evolution. RESULTS: The initial selection included 34 possible donors, of which 12 (35.2%) were viable donors from whom 22 (32.3%) kidneys were recovered. There was a correlation between the highest capnometry values and less need for post-transplant dialysis (≥24 mmHg, p < 0.017), fewer dialysis sessions and fewer days to recover correct renal function (Rho -0.47, p < 0.044). There was a significant inverse correlation between the capnometry values at transfer and 1-month post-transplant creatinine levels (Rho -0.62, p < 0.033). There were no significant differences between the capnometry values at transfer and primary nonfunction (PNF) or warm ischaemia time. One-year patient survival was 100% for patient receiving organ donation, while graft survival was 95%. CONCLUSIONS: Capnometry levels at transfer are a useful predictor of the short-term function and viability of kidney transplants from uncontrolled donations after circulatory death.

A Multifaceted Educational Intervention in the Doctor-Patient Relationship for Medical Students to Incorporate Patient Agendas in Simulated Encounters.

From the beginning of their clinical training, medical students demonstrate difficulties when incorporating patient perspectives. This study aimed to assess if students, after an instructional programme, increased their sensitivity towards patients' needs and carried out bidirectional conversations. An observational study involving 109 medical students prior to their clerkships was designed. They attended a five-step training programme designed to encourage the use of communication skills (CSs) to obtain patients' perspectives. The course developed experiential and reflective educational strategies. The students improved their use of CSs throughout three sessions, and the overall score for these patient consultations went up in the opinions of both the external observer (EO) (5; 6.6; 7.5) and the simulated patients SPs (5.3; 6.6; 7.8). Most of the students (83.9%) considered that the CSs addressed were useful for clinical practice, particularly the interviews and the feedback received by the SP and the lecturer. The programme seems to help the students use CSs that facilitate a more bidirectional conversation in a simulated learning environment. It is feasible to integrate these skills into a broader training programme. More research is needed to assess whether the results are applicable to students in real settings and whether they influence additional outcomes.

A Paradoxical Clinical Coincidence: Benign Paroxysmal Positional Vertigo and Bilateral Vestibulopathy.

Benign paroxysmal positional vertigo (BPPV) and bilateral vestibulopathy (BVL) are two completely different forms of vestibular disorder that occasionally occur in the same patient. We conducted a retrospective review searching for that coincidence in our database of the patients seen over a 15-year period and found this disorder in 23 patients, that is 0.4%. More frequently they occurred sequentially (10/23) and BPPV was diagnosed first. Simultaneous presentation occurred in 9/23 patients. It was subsequently studied, but in a prospective manner, in patients with BPPV on all of whom a video head impulse test was performed to search for bilateral vestibular loss; we found it was slightly more frequent (6/405). Both disorders were treated accordingly, and it was found that the results follow the general trend in patients with only one of those disorders.

High-Content Phenotypic Screen of a Focused TCAMS Drug Library Identifies Novel Disruptors of the Malaria Parasite Calcium Dynamics.

The search for new antimalarial drugs with unexplored mechanisms of action is currently one of the main objectives to combat the resistance already in the clinic. New drugs should target specific mechanisms that once initiated lead inevitably to the parasite's death and clearance and cause minimal toxicity to the host. One such new mode of action recently characterized is to target the parasite's calcium dynamics. Disruption of the calcium homeostasis is associated with compromised digestive vacuole membrane integrity and release of its contents, leading to programmed cell death-like features characterized by loss of mitochondrial membrane potential and DNA degradation. Intriguingly, chloroquine (CQ)-treated parasites were previously reported to exhibit such cellular features. Using a high-throughput phenotypic screen, we identified 158 physiological disruptors (hits) of parasite calcium distribution from a small subset of approximately 3000 compounds selected from the GSK TCAMS (Tres Cantos Anti-Malarial Set) compound library. These compounds were then extensively profiled for biological activity against various CQ- and artemisinin-resistant Plasmodium falciparum strains and stages. The hits were also examined for cytotoxicity, speed of antimalarial activity, and their possible inhibitory effects on heme crystallization. Overall, we identified three compounds, TCMDC-136230, -125431, and -125457, which were potent in inducing calcium redistribution but minimally inhibited heme crystallization. Molecular superimposition of the molecules by computational methods identified a common pharmacophore, with the best fit assigned to TCMDC-125457. There were low cytotoxicity or CQ cross-resistance issues for these three compounds. IC50 values of these three compounds were in the low micromolar range. In addition, TCMDC-125457 demonstrated high efficacy when pulsed in a single-dose combination with artesunate against tightly synchronized artemisinin-resistant ring-stage parasites. These results should add new drug options to the current armament of antimalarial drugs as well as provide promising starting points for development of drugs with non-classical modes of action.