Is membrane sweeping beneficial at the initiation of labor induction?

Objective: To determine whether cervical membrane sweeping during labor induction is beneficial.

Methods: Outcomes of labor after induction in pregnant women at term were compared in a randomized trial. Women were assigned to having their membranes “swept” or “not swept” at the initiation of labor induction.

Results: We recruited a total of 870 women of which 70 were excluded. There were 400 nullipara (Group A) [198 “swept”, 202 “not swept”] and 400 multiparas (Group B) (201 “swept” and 199 “not swept”]. Among group A who received intravaginal prostaglandin (PG) E₂, those who had simultaneous sweeping had significantly shorter mean induction-labor interval (12.9?±?1.3 versus 16.2?±?1.1 hours, p?=?0.046), lower mean dose of oxytocin (6.6?±?0.6 versus 10.11?±?1.4?mU/minute, p?=?0.01), and increased normal delivery rates (vaginal delivery 82.8% versus 58.6%, p?=?0.01). Sweeping also had a favorable effect on nulliparas who had ARM and received oxytocin alone (mean induction-labor interval 5.9?±?2.9 versus 10.9?±?2.6 hours p?=?0.04, mean maximum dose of oxytocin 9.8?±?1.1 versus 15.2?±?1.1?mU/min, p?=?0.01). These results were restricted to women with unfavorable cervix in Group A those who had membrane sweeping.

Conclusion: Membrane sweeping, has beneficial effects on labor and delivery, which is limited to nulliparas with unfavorable cervix requiring PGE₂ or Oxytocin alone.     

T‐cell responses and therapies against SARS‐CoV‐2 infection

Coronavirus disease 2019 (COVID‐19) is caused by SARS‐CoV‐2, a novel coronavirus strain. Some studies suggest that COVID‐19 could be an immune‐related disease, and failure of effective immune responses in initial stages of viral infection could contribute to systemic inflammation and tissue damage, leading to worse disease outcomes. T cells can act as a double‐edge sword with both pro‐ and anti‐roles in the progression of COVID‐19. Thus, better understanding of their roles in immune responses to SARS‐CoV‐2 infection is crucial. T cells primarily react to the spike protein on the coronavirus to initiate antiviral immunity; however, T‐cell responses can be suboptimal, impaired or excessive in severe COVID‐19 patients. This review focuses on the multifaceted roles of T cells in COVID‐19 pathogenesis and rationalizes their significance in eliciting appropriate antiviral immune responses in COVID‐19 patients and unexposed individuals. In addition, we summarize the potential therapeutic approaches related to T cells to treat COVID‐19 patients. These include adoptive T‐cell therapies, vaccines activating T‐cell responses, recombinant cytokines, Th1 activators and Th17 blockers, and potential utilization of immune checkpoint inhibitors alone or in combination with anti‐inflammatory drugs to improve antiviral T‐cell responses against SARS‐CoV‐2.     

Prognostic significance of an elevated creatine kinase in the absence of an elevated troponin I during an acute coronary syndrome

In patients with troponin-negative acute coronary syndromes, creatine kinase (CK)-MB elevation predicts a significantly higher risk of death and major acute cardiac events compared with CK-MB negative patients. This risk is accentuated in troponin-negative, CK-MB positive patients who do not demonstrate ST elevation by electrocardiogram.     

Exposure to war trauma and PTSD among parents and children in the Gaza strip

Objective Exposure to war trauma has been independently associated with posttraumatic stress (PTSD) and other emotional disorders in children and adults. The aim of this study was to establish the relationship between ongoing war traumatic experiences, PTSD and anxiety symptoms in children, accounting for their parents’ equivalent mental health responses. Methods The study was conducted in the Gaza Strip, in areas under ongoing shelling and other acts of military violence. The sample included 100 families, with 200 parents and 197 children aged 9–18 years. Parents and children completed measures of experience of traumatic events (Gaza Traumatic Checklist), PTSD (Children’s Revised Impact of Events Scale, PTSD Checklist for parents), and anxiety (Revised Children’s Manifest Anxiety Scale, and Taylor Manifest Anxiety Scale for parents). Results Both children and parents reported a high number of experienced traumatic events, and high rates of PTSD and anxiety scores above previously established cut-offs. Among children, trauma exposure was significantly associated with total and subscales PTSD scores, and with anxiety scores. In contrast, trauma exposure was significantly associated with PTSD intrusion symptoms in parents. Both war trauma and parents’ emotional responses were significantly associated with children’s PTSD and anxiety symptoms. Conclusions Exposure to war trauma impacts on both parents’ and children’s mental health, whose emotional responses are inter-related. Both universal and targeted interventions should preferably involve families. These could be provided by non-governmental organizations in the first instance.     

Immunological response and overall survival in a subset of advanced renal cell carcinoma patients from a randomized phase 2/3 study of naptumomab estafenatox plus IFN-α versus IFN-α

Naptumomab estafenatox/ABR-217620/ANYARA (Nap) has been evaluated in clinical phase 1 and 2/3 studies. RCC patients in the phase 2/3 trial were randomized 1:1 in an open label study to receive Nap+IFN-α or IFN-α. In this study, we analyzed the UK patients for their immunological response in relation to prolonged overall survival (OS). We found that Nap-specific T cells were reduced after 3 treatment days in patients'' peripheral blood. Levels of both Nap-specific CD4⁺ and CD8⁺ T cells were significantly higher 8 days after the first treatment. Patients with such pattern of reduction and expansion of Nap-binding T cells also showed increased levels of IL-2 and IFN-γ in plasma 3 hours after the first Nap treatment. In addition, Nap caused an increase of IL-6, IL-10 and TNF-α. The patients in the UK subset showed a tendency of OS benefit after Nap treatment. Most Nap treated patients with long OS had low baseline IL-6 and normal levels of anti-SEA/E-120 antibodies. Furthermore, patients with pronounced Nap induced IL-2 and T cell expansion had long OS. In conclusion, patients with low baseline IL-6 and normal anti-SEA/E-120 may respond well to Nap by T cell activation and expansion paving the way for anti-tumour effects.     

Helios,and not FoxP3, is the marker of activated Tregs expressing GARP/LAP

Regulatory T cells (Tregs) are key players of immune regulation/dysregulation both in physiological and pathophysiological settings. Despite significant advances in understanding Treg function, there is still a pressing need to define reliable and specific markers that can distinguish different Treg subpopulations. Herein we show for the first time that markers of activated Tregs [latency associated peptide (LAP) and glycoprotein A repetitions predominant (GARP, or LRRC32)] are expressed on CD4⁺FoxP3⁻ T cells expressing Helios (FoxP3⁻Helios⁺) in the steady state. Following TCR activation, GARP/LAP are up-regulated on CD4⁺Helios⁺ T cells regardless of FoxP3 expression (FoxP3^+/−Helios⁺). We show that CD4⁺GARP^+/−LAP⁺ Tregs make IL-10 immunosuppressive cytokine but not IFN-γ effector cytokine. Further characterization of FoxP3/Helios subpopulations showed that FoxP3⁺Helios⁺ Tregs proliferate in vitro significantly less than FoxP3⁺Helios⁻ Tregs upon TCR stimulation. Unlike FoxP3⁺Helios⁻ Tregs, FoxP3⁺Helios⁺ Tregs secrete IL-10 but not IFN-γ or IL-2, confirming they are bona fide Tregs with immunosuppressive characteristics. Taken together, Helios, and not FoxP3, is the marker of activated Tregs expressing GARP/LAP, and FoxP3⁺Helios⁺ Tregs have more suppressive characteristics, compared with FoxP3⁺Helios⁻ Tregs. Our work implies that therapeutic modalities for treating autoimmune and inflammatory diseases, allergies and graft rejection should be designed to induce and/or expand FoxP3⁺Helios⁺ Tregs, while therapies against cancers or infectious diseases should avoid such expansion/induction.