The natural killer cell activating receptor,NKG2D,is critical to antibody-dependent chronic rejection in heart transplantation

Chronic rejection is among the most pressing clinical challenges in solid organ transplantation. Interestingly, in a mouse model of heterotopic heart transplantation, antibody-dependent, natural killer (NK) cell-mediated chronic cardiac allograft vasculopathy occurs in some donor–recipient strain combinations, but not others. In this study, we sought to identify the mechanism underlying this unexplained phenomenon. Cardiac allografts from major histocompatibility complex (MHC) mismatched donors were transplanted into immune-deficient C57Bl/6.rag^−/− recipients, followed by administration of a monoclonal antibody against the donor MHC class I antigen. We found marked allograft vasculopathy in hearts from C3H donors, but near-complete protection of BALB/c allografts from injury. We found no difference in recipient NK cell phenotype or intrinsic responsiveness to activating signals between recipients of C3H versus BALB/c allografts. However, cardiac endothelial cells from C3H allografts showed an approximately twofold higher expression of Rae-1, an activating ligand of the NK cell receptor natural killer group 2D (NKG2D). Importantly, the administration of a neutralizing antibody against NKG2D abrogated the development of allograft vasculopathy in recipients of C3H allografts, even in the presence of donor-specific antibodies. Therefore, the activating NK cell receptor NKG2D is necessary in this model of chronic cardiac allograft vasculopathy, and strain-dependent expression of NK activating ligands correlates with the development of this disease.     

How to define pathologic pelvic floor descent in MR defecography during defecation?

Abdominal Radiology - To assess the extents of pelvic floor descent both during the maximal straining phase and the defecation phase in healthy volunteers and in patients with pelvic floor...     

Comparing Diazepam Plus Fentanyl With Midazolam Plus Fentanyl in the Moderate Procedural Sedation of Anterior Shoulder Dislocations: A Randomized Clinical Trial

BackgroundThe reduction of shoulder dislocation requires adequate procedural sedation and analgesia. The mixture of midazolam and fentanyl is reported in the literature, but long-acting benzodiazepines in conjunction with fentanyl are lacking.Study ObjectiveOur aim was to compar e IV diazepam with IV midazolam in moderate procedural sedation (based on the classification of the American Society of Anesthesiologists) for the reduction of shoulder dislocation.MethodsThis was a randomized controlled clinical trial conducted from April 2019 to December 2019 in the emergency department of a university-affiliated hospital in Tehran, Iran. Participants were adult patients (aged 18–65 years) with anterior shoulder dislocation. Group A (n = 42) received diazepam 0.1 mg/kg plus fentanyl 1 μg/kg IV and group B received midazolam 0.1 mg/kg plus fentanyl 1 μg g/kg IV. Main outcomes measured were onset of muscle relaxation, time taken to reduction, total procedure time, number of the reduction attempts, patient recovery time, the occurrence of the adverse effects, amount of the pain reported by the patients using visual analog scale, and patients and physicians overall satisfaction with the procedure using a Likert scale question.ResultsEighty-one patients were included. The mean ± standard deviation time of the onset of the muscle relaxation and time taken to reduction was shorter in the diazepam plus fentanyl group (p = 0.016 and p = 0.001, respectively). Adverse effects and pain relief were not statistically different between the two groups. Patient recovery time and total procedure time was shorter in the midazolam plus fentanyl group (p = 0.008 and p = 0.02, respectively). The overall satisfaction of patients and physicians was higher in the diazepam plus fentanyl group.ConclusionsAs compared with midazolam plus fentanyl, diazepam plus fentanyl was superior in terms of the onset of the muscle relaxation, patient and physician satisfaction, and time taken to reduction.     

The objective CORE score allows early rule out in acute chest pain patients

Abstract

Objectives. Chest pain is a common complaint in the emergency department (ED), and it is a challenge to identify low-risk chest pain patients eligible for early discharge. We aimed to develop a simple objective decision rule to exclude 30-day major adverse cardiac events (MACE) in ED chest pain patients.

Design. We analyzed prospectively included patients presenting with chest pain. Low risk patients were identified with the clinical objective rule-out evaluation (CORE). CORE was based on high sensitivity cardiac troponin T (hs-cTnT) tests at ED presentation (0?h) and 2?h later together with a simplified risk score consisting of four objective variables: age ≥65 years and a history of arterial disease, hypertension or diabetes. For the patient to be classified as low risk in the CORE rule, hs-cTnT had to be ≤14?ng/L both at 0 and 2?h, and the sum of the risk score had to be 0. The primary outcome was MACE within 30 days.

Results. Among the 751 patients in the final analysis, 90 (11.9%) had a MACE. CORE identified 248 (33%) of patients as low risk with a sensitivity of 98.9% (CI 93.1–99.9) and a negative predictive value of 99.6% (95% CI 97.4–100) for 30-day MACE. Adding the ED physician’s interpretation of the ECG to CORE did not improve diagnostic performance.

Conclusion. A simple objective decision rule (CORE) identified one-third of all patients as having a very low 30-day risk of MACE. These patients may potentially be discharged without additional investigations for acute coronary syndrome.     

Self-poisonings with drugs by adolescents in the Lund catchment area

Our objective was to investigate which drugs young people who attempt suicide use in the Lund catchment area eight municipalities in Skåne, southern Sweden. All patients aged up to 18 years admitted to Lund University Hospital after deliberate or probably deliberate self-poisoning from 1 January 1991 until 31 December 1995 were included. Forty-nine (58%) had used a single drug; 20 (24%) had used 3 or more drugs. Fifty-two (61%) used analgesics paracetamol was used by 38 (45%) and propoxyphene by 17 (20%). Thirty-one (36%) had ingested psychotropics 13 used benzodiazepines, 10 antidepressants, and 8 antipsychotics. Eleven (15%) had used drugs in combination with alcohol. We conclude that it is important to follow changes in self-poisoning patterns, to monitor the effects of preventive work and discover new trends in drug use.