Deactivation of alveolar macrophages in septic neutropenic ARDS

STUDY OBJECTIVES: Neutrophils often have been involved in the pathophysiology of ARDS. However, authentic ARDS has been described in patients with severe neutropenia, suggesting the presence of other potential mechanisms that are responsible of this syndrome. Alveolar macrophages (AMs) could be involved in the development of ARDS, and so we decided to study AM activation in neutropenic patients. PATIENTS: We designed a prospective study and enrolled two subgroups of consecutive patients (group A, 18 patients; group B, 22 patients) with septic ARDS. In the first period, 7 of 18 patients were neutropenic, and in the second period 10 of 22 patients were neutropenic. All neutropenic patients were treated with granulocyte colony-stimulating factor (G-CSF). Measurements and results: In group A, BAL fluid samples were analyzed for differential and total cell counts, and alveolar activation marker expression (ie, human leukocyte antigen [HLA]-DR locus) was determined. Basal and lipopolysaccharide (LPS)-stimulated production of tumor necrosis factor, interleukin (IL)-1 beta, IL-6, and IL-10 was evaluated in group B. In neutropenic patients, the BAL fluid total cell count and the neutrophil absolute count was significantly lower compared to those in nonneutropenic patients (p = 0.029 and p = 0.046, respectively). HLA-DR expression on AMs was significantly decreased (p = 0.016), and the percentage of AMs expressing HLA-DR was also significantly lower (p = 0.041). In neutropenic patients, the mean percentage of AMs expressing HLA-DR was significantly lower in deceased patients compared to survivors (30 +/- 7 vs 43 +/- 1, respectively; p = 0.047). Basal AMs released cytokines was comparable between the two groups; however, LPS stimulation yielded a deactivation of AMs in neutropenic patients. CONCLUSION: These results suggest a deactivation and/or hypoactivation of AMs in septic ARDS patients. This deactivation/hypoactivation could be linked to the use of G-CSF as this molecule has been shown to generate a down-regulation of HLA-DR expression.     

Failure of ES 52, a highly potent enkephalinase inhibitor, to affect nociceptive transmission by rat dorsal horn convergent neurones

The effects of ES 52, a highly potent derivative of the enkephalinase (enkephalin-dipeptidylcarboxypeptidase) inhibitor thiorphan, were studied on nociceptive activities of dorsal horn convergent neurones in the anaesthetized rat. Neither the C-fibre component of the responses elicited by supramaximal electrical stimulation of the hindpaw excitatory receptive fields nor diffuse noxious inhibitory controls triggered by immersion of the tail in 46-48 degrees C waterbaths, were affected by ES 52. Thus we conclude that, in our experimental conditions, modulations of the transmission of nociceptive messages at the spinal level are not greatly modified by specifically blocking the degradation of enkephalins. If a major role for enkephalinase (vs aminopeptidase) in the catabolism of enkephalins at the spinal level can be confirmed, then comparison of the present data with our previous results obtained using the opioid antagonist naloxone, might suggest a predominant role for proenkephalin B products (i.e. dynorphins and/or alpha-neo-endorphin) in modulating nociceptive transmission in the spinal cord.     

In vivo protection against scorpion toxins by liposomal immunization

The possibility of raising a humoral immune response able to induce protection from the lethal effects of scorpion toxins was evaluated in the mouse model. A toxic fraction from the venom of the scorpion Tityus serrulatus was entrapped in sphingomyelin-cholesterol liposomes which yielded a conveniently detoxified immunogen. After three injections of this immunogen, all but three of a group of 18 mice developed an IgG response which was shown to be both specific and of good affinity for the toxic antigen. In vitro neutralization assays indicated that pre-incubation of a lethal dose of the toxic fraction with immune sera strongly diminished its toxicity. In vivo protection assays showed that mice with the highest levels of circulating anti-toxin antibodies could resist the challenge by double the normal LD₅₀ of the toxic fraction, which killed all control non-immune mice. The protection was, however, found to be limited both in its duration and its effectiveness against higher amounts of toxin.     

Outcome of pregnancies in patients with anti‐SSA/Ro antibodies: A study of 165 pregnancies,with special focus on electrocardiographic variations in the children and comparison with a control group

Objective

Aside from congenital heart block (CHB), sinus bradycardia and prolongation of the corrected QT (QTc) interval have been reported in infants born to mothers with anti‐SSA antibodies. To assess the pathologic nature of these manifestations, this study focused on electrocardiographic (EKG) variations in these children, comparing them with findings in a control group.

Methods

We studied 165 consecutive pregnancies in 106 anti‐SSA–positive women with connective tissue diseases (CTDs). EKGs obtained on 58 children of this group were compared with those obtained on 85 infants born to mothers with CTD who were negative for both anti‐SSA and anti‐SSB.

Results

No statistically significant difference was seen between the 2 study groups with regard to gestational age, prematurity, birth weight, age of the children at the time of EKG, age of the mothers, or treatments received by the mothers during their pregnancies. Seven of 137 children developed cutaneous neonatal lupus syndrome; 1 child developed CHB (CHB risk of 1 in 99 [1%] if only the first prospectively observed pregnancy in women without a history of CHB is included in the analysis). For EKGs recorded during the first 2 months of life, the mean ± SD PR interval was 96 ± 16 msec in the anti‐SSA–positive group and 96 ± 13 msec in the anti‐SSA–negative group (P = 0.84), with mean QTc values of 397 ± 27 and 395 ± 25 msec (P = 0.57) and mean heart rates of 141 ± 23 and 137 ± 21 beats per minute (P = 0.20), respectively. No difference in the PR interval, QTc interval, or heart rate was observed for EKGs obtained between 2 and 4 months of life. When EKGs obtained at 0–2 months were compared with those obtained at 2–4 months, a physiologic prolongation of the QTc interval was observed in both study groups. No sudden infant death or symptomatic arrhythmia occurred during the first year of life.

Conclusion

The EKG findings in children of anti‐SSA–positive and anti‐SSA–negative mothers were not significantly different. Our results suggest that the prolongation of the QTc interval and sinus bradycardia that have recently been reported in children of mothers with anti‐SSA antibodies occur independently of the anti‐SSA antibodies. The pathologic nature of these EKG variations was not confirmed by our controlled study.

     

Posterior pelvic exenteration for ovarian cancer: surgical and oncological outcomes

ObjectivePosterior pelvic exenteration (PPE) can be required to achieve complete resection in ovarian cancer (OC) patients with large pelvic disease. This study aimed to analyze morbidity, complete resection rate, and survival of PPE.MethodsNinety patients who underwent PPE in our Comprehensive Cancer Center between January 2010 and February 2021 were retrospectively identified. To analyze practice evolution, 2 periods were determined: P1 from 2010 to 2017 and P2 from 2018 to 2021.ResultsA 82.2% complete resection rate after PPE was obtained, with rectal anastomosis in 96.7% of patients. Complication rate was at 30% (grade 3 in 9 patients), without significant difference according to periods or quality of resection. In a binary logistic regression adjusted on age and stoma, only age of 51–74 years old was associated with a lower rate of complication (odds ratio=0.223; p=0.026). Median overall and disease-free survivals (OS and DFS) from initial diagnosis were 75.21 and 29.84 months, respectively. A negative impact on OS and DFS was observed in case of incomplete resection, and on DFS in case of final cytoreductive surgery (FCS: after ≥6 chemotherapy cycles). Age ≥75-years had a negative impact on DFS for new OC surgery. For patients with complete resection, OS and DFS were decreased in case of interval cytoreductive surgery and FCS in comparison with primary cytoreductive surgery.ConclusionPPE is an effective surgical measure to achieve complete resection for a majority of patients. High rate of colorectal anastomosis was achieved without any mortality, with acceptable morbidity and high protective stoma rate.     

Self-rehabilitation combined with botulinum toxin to improve arm function in people with chronic stroke. A randomized controlled trial

BackgroundBotulinum toxin injection (BTI) reduces muscle hyperactivity, but its effect on active upper-limb function is limited. Intensive rehabilitation could optimize the effects; however, outpatient post-stroke rehabilitation is usually not intensive. One solution could be self-rehabilitation.ObjectivesThe aim of this randomized controlled trial was to determine the effect of a self-rehabilitation program combined with BTI on upper-limb function in individuals with chronic hemiparesis.MethodsIn total, 33 outpatients were randomly allocated to receive BTI + self-rehabilitation (R group: n = 17) or BTI alone (C group: n = 16). Outcomes evaluated just before the BTI and 4 weeks later included the Wolf Motor Function Test (WMFT time: primary outcome), Action Research Arm Test, fatigue and quality of life.ResultsChange in WMFT did not differ between groups at 4 weeks (WMFT time: ?14% for R group, ?4% for C group. WFMT score: +12% for R group, 0% in C group). WFMT time and score improved significantly in the R group only (?14%, P = 0.01, and +12%, P = 0.02). In addition, the proportion of patients with improved WMFT time and score was higher in the R than C group (R group: 71% improved score, 77% improved time; C group: 43% improved score, 50% improved time). Also, passive range of shoulder flexion (P = 0.03) and wrist extension (P = 0.01) improved only in the R group. No other variables changed significantly. Compliance was excellent; average daily training time was greater than that prescribed.ConclusionsThe addition of a self-rehabilitation program to BTI did not significantly improve functional outcomes more than BTI alone; however, movement quality and speed improved only in the self-rehabilitation group. Participants in the self-rehabilitation group trained more than they were asked to, which suggests that they found the program worthwhile. These clinically relevant findings justify larger-scale studies of the effects of self-rehabilitation to enhance the effects of BTI. Clinical trial: NCT02699762.