Feasibility Of Therapy Research Articles

CAR-NK Cells Enhanced by GITRL Expression: An Effective and Feasible Therapy for GD2+ Solid Tumors

CAR-NK Cells Enhanced by GITRL Expression: An Effective and Feasible Therapy for GD2+ Solid Tumors

Adenine base editing of CFTR using receptor targeted nanoparticles restores function to G542X cystic fibrosis airway epithelial cells

The cystic fibrosis (CF) causing variant G542X harbours a premature translation stop signal in the cystic fibrosis transmembrane conductance regulator (CFTR) mRNA. This results in nonsense-mediated decay and loss of functional CFTR protein which leads to defective anion transport and the development of CF disease pathology. Currently available CF modulator therapies cannot be used to treat this variant. We used an adenine base editor (ABE8e Cas9) and guide RNA (sgRNA)/enhanced green fluorescent protein (EGFP) plasmids encapsulated in receptor targeted nanoparticles (RTN), delivered to Bmi-1 transduced basal human CF nasal epithelial cells harbouring the homozygous CFTR G542X variant, to convert the stop codon to G542R, a variant which is amenable to modulator therapy. ABE resulted in 17% of alleles edited to G542R and further selection of GFP fluorescent cells by FACS liberated a population with 52% G542R edited alleles with no editing of neighbouring adenines (A) and few off target edits using a gRNA homology-based approach. In cells differentiated at air–liquid-interface (ALI), 17% and 52% editing of CFTR G542X increased mRNA abundance. 52% editing alone or 17% and 52% editing of CFTR G542X plus treatment with CFTR modulators (VX-445/VX-661/VX-770; ETI/Trikafta/Kaftrio) increased epithelial CFTR protein expression, CFTR protein band C abundance, CFTR172 inhibitable anion transport, and changes in airway surface liquid height and pH in response to vasoactive intestinal peptide (VIP) stimulation. Epithelial scratch repair speed and directionality was also improved. These data provide proof-of-concept that ABE of G542X to G542R in human CF airway epithelial cells could provide a feasible therapy for this variant.Graphical abstract

Programmed enhancement of endogenous iron-mediated lysosomal membrane permeabilization for tumor ferroptosis/pyroptosis dual-induction

Ferroptosis and pyroptosis, as emerging regulated forms of cell death capable of overcoming apoptotic resistance, demonstrate promising potential in tumor therapy. Given that iron manipulation and reactive oxygen species elevation serve as common stimuli for both processes, inducing lysosomal membrane permeabilization (LMP) with ensuing release of lysosomal contents (including iron ions and cathepsins) is anticipated to realize dual induction of ferroptosis/pyroptosis. Herein, we report a folic acid and croconaine molecule-functionalized upconversion nanoparticle (UCNP-Cro/FA) that is able to mobilize intracellular stores of endogenous iron and spatiotemporally control the lysosome-intrinsic Fenton chemistry, thereby triggering LMP-associated cell death. The process of endogenous iron mobilization occurs through two key steps: Cro-mediated coordination of abundant Fe3+ ions within lysosomes, followed by UV-emitting upconversion core-mediated photoreduction, resulting in Fe2+ ions release. Both in vitro and in vivo experiments show that UCNP-Cro/FA + NIR treatment effectively boost LMP by endogenous iron-mediated •OH production, ultimately triggering irreversible tumor cell death via ferroptosis and Caspase-1/GSDMD-dependent pyroptosis pathways. Moreover, this process potentiates tumor immunogenicity, holding promise for tumor immunotherapy. Overall, this work proposes a feasible tumor therapy strategy that integrates ferroptosis and pyroptosis through the efficient application and activation of endogenous iron.

GRP78 Nanobody-Directed Immunotoxin Activates Innate Immunity Through STING Pathway to Synergize Tumor Immunotherapy.

The lack of targetable antigens poses a significant challenge in developing effective cancer-targeted therapies. Cell surface translocation of endoplasmic reticulum (ER) chaperones, such as glucose-regulated protein 78 (GRP78), during malignancy, drug resistance, and ER stress induced by therapies, offers a promising pan-cancer target. To target GRP78, nanobody C5, identified from a phage library and exhibiting high affinity for human and mouse GRP78, is utilized to develop the Pseudomonas exotoxin (PE) immunotoxin C5-PE38. C5-PE38 induced ER stress, apoptosis and immunogenic cell death in targeted cells and showed antitumor efficacy against colorectal cancer and melanoma models without obvious toxicity. Mechanistically, transcriptome profiling showed that C5-PE38 reshaped the tumor immune microenvironment with enhanced innate and adaptive immune response and response to interferon beta. Moreover, C5-PE38-induced cell death could trans-activate STING pathway in dendritic cells and macrophages, promoting CD8+ T cell infiltration. It also sensitizes both primary and metastatic melanomas to anti-PD1 therapy, partly through STING activation. Overall, this study unveils a feasible GRP78 nanobody-directed therapy strategy for single or combinatorial cancer intervention. This work finds that C5-PE38-induced cell death stimulates STING-dependent cytosolic DNA release to promote antitumor immunity, a mechanism not previously reported for PE38, providing valuable insights for its clinical use.

Invitro Evaluation of the Anti-Inflammatory Activity of Phloroglucinol and Alpha-lipoic acid

It was decided to test the anti-inflammatory activity of phloroglucinol and alpha-lipoic acid combined in order to evaluate the possibility of a synergistic effect in the battle against inflammation. Both the antioxidant alpha-lipoic acid and the naturally occurring phenolic compound phloroglucinol were investigated by researchers in order to ascertain whether or not they were capable of modulating inflammatory pathways and pathways in vitro. The effects of the combination on numerous inflammatory mediators, including cytokines (TNF-α, IL-1β, and IL-6), prostaglandin E2 (PGE2), and nitric oxide (NO) generation, were assessed by employing human peripheral blood mononuclear cells (PBMCs) that were cultivated. The results demonstrated that these pro-inflammatory markers were greatly reduced following the combination treatment, which may indicate that the combination treatment had a synergistic effect on reducing inflammation. Furthermore, the combination had a considerable impact on inhibiting the activation of nuclear factor-kappa B (NF-κB), which is an essential regulator of inflammation. These findings imply that the combination of phloroglucinol and alpha-lipoic acid could be a feasible therapy method for inflammatory disorders; nevertheless, additional in vivo research are required to establish the efficacy and safety of the combination.

Current Evidence of Probiotics in Pediatrics with Short Bowel Syndrome, Is It Safe and Beneficial? A Literature Review

Background: Short Bowel Syndrome (SBS) presents significant challenges in pediatric care, particularly due to its high incidence in neonates and the associated health burdens, including elevated mortality rates primarily from hepatic failure and sepsis. SBS in infants and young children primarily arises from congenital defects or acquired conditions that necessitate significant bowel resection. The predominant cause of SBS during the neonatal period is necrotizing enterocolitis (NEC), accounting for 35% to 50% of cases. In older children, SBS is frequently associated with midgut volvulus or traumatic injuries. Discussion: Managing pediatric SBS requires a multidisciplinary approach that involves evaluating dietary, pharmacology, and surgical factors. Key strategies focus on improving absorptive capacity, promoting intestinal adaptation, and regulating bowel motility. In infants and young children, SBS often leads to a range of complications, including nutrient deficiencies, fluid imbalances, and growth delays. The condition necessitates careful medical management to address these challenges and promote optimal health outcomes. Recent studies have investigated probiotics as an adjuvant treatment for SBS, demonstrating enhanced growth, nutritional status, and inhibition of harmful microbes in afflicted children Conclusion: The use of probiotics in children with SBS has shown both safety and beneficial effects, making it a feasible alternative therapy in routine medical practice. However, the lack of significant clinical data highlights the need for more study to better understand the efficacy of probiotics in the treatment of SBS.

PD-1 inhibitor (sintilimab) and fruquintinib plus SOX as conversion therapy for initially unresectable gastric/gastroesophageal junction adenocarcinoma (GC/GEJC): Updated results from a single-arm, phase 2 clinical trial.

406 Background: The evidence of conversion therapy for unresectable GC/GEJC is limited. Previously, preliminary results of the ongoing open-label, phase 2 study (NCT05177068) have showed promising R0 surgical conversion rate (62.1%), R0 resection rate (100%) and acceptable tolerability in unresectable GC/GEJC with sintilimab and fruquintinib plus SOX (ASCO 2024). Here we present updated results with longer follow-up duration, including more enrolled patients. Methods: Eligible patients were administered fruquintinib (4mg/d, po, qd, d1-14), sintilimab (200mg, iv, d1), oxaliplatin (130 mg/m 2 , iv, d1) and S-1 (40-60mg based on BSA, po, bid, d1-14) every 3 weeks for 3 or 6 cycles. One more cycle of sintilimab plus SOX was given before resection. Patients were assessed for tumor response and surgical feasibility by radiologic imaging & MDT every 3 cycles. Primary endpoint was R0 resection rate. Secondary endpoints included pathological response, ORR, PFS, OS, and safety. Results: As of July 30, 2024, 42 pts (37 males/5 females) with a median age of 64 years (range: 43–76), 71% ECOG PS1, 55% GEJC were enrolled. Nine (21.4%) of the 42 pts had distant metastasis and five (11.9%) pts had more than one unresectable factors. The most common unresectable factors were extensive or bulky lymph nodes 54.8% (23), liver metastasis 11.9% (5), peritoneal metastasis 4.8% (2), para-aortic lymph node metastasis 2.4% (1), and local progression 38.1% (16). Of 35 evaluable pts, ORR was 68.6% and DCR was 97.1%. Among the 29 pts who had completed surgical conversion, the R0 resection rate was 100% (29/29) and R0 surgical conversion rate was 82.9% (29/35). 10.3% (3/29) pts achieved pathological complete response (pCR), and 20.7% (6/29) pts reached tumor regression grade (TRG) 0-1. Additionally, the pathological response rate (pRR) according to JCGC (≥ Grade 1b) was 93.1% (27/29). Seven pts (16.7%) had grade 3 treatment-emergent adverse events, including 4 cases of anemia, 2 cases of neutrophil count decreased, and 1 case of each (lymphocyte count decreased, gastrointestinal hemorrhage, diarrhea, and immune-related pneumonitis). No severe surgery-related complication was observed. Conclusions: Fruquintinib combined with sintilimab and SOX yielded very high R0 conversion rate and R0 resection rate with a manageable safety profile in unresectable GC/GEJC, representing a potential and feasible conversion therapy regimen for this population. Survival data will continue to be followed up. Clinical trial information: NCT05177068 .

Endoscopic hemostasis with a self-expandable metal stent as bridge therapy for hemobilia.

Management of hemobilia is often challenging. Recently, endoscopic hemostasis with a self-expandable metal stent (SEMS) has shown promising efficacy for controlling bleeding at the endoscopic sphincterotomy site. This study aimed to assess efficacy and feasibility of endoscopic hemostasis as bridge therapy for hemobilia. Patients with hemobilia between 2008 and 2023 were retrospectively reviewed. We compared efficacy of hemostasis between the initial endoscopic hemostasis group (ENDO group) and the initial angiographic embolization group (EMBO group). The primary outcome was initial hemostasis success rate and the secondary outcomes were delayed bleeding rate, subsequent embolization rate, 28-day mortality, transfusion amount, time to first hemostasis, total hemobilia time, and incidence of hypovolemic shock. A total of 26 patients with hemobilia were included in this study and 17 patients (65.4%) were identified as the ENDO group and nine patients (34.6%) were classified as the EMBO group. The success rate of initial hemostasis was 88.2% (15/17) in the ENDO group and 100% (9/9) in the EMBO group ( P = 0.529). The rate of delayed bleeding in the ENDO group was 17.6% (3/17) and 0.0% (0/9) in the EMBO group ( P = 0.529). Total hemobilia time was shorter in the ENDO group than in the EMBO group (mean: 281.5 ± 1022.4 minutes vs. 5002.8 ± 7982.6 minutes; P < 0.001) Stent insertion depth was associated with successful hemostasis without delayed bleeding. ( P = 0.015). Endoscopic hemostasis using SEMS for hemobilia appeared to be a feasible bridge therapy.

New Perspectives on Antimicrobial Agents: Omadacycline for community-acquired pneumonia, skin and soft tissue infections, and nontuberculous mycobacteria (focus on M. abscessus).

Omadacycline is a novel antimicrobial belonging to the tetracycline class. It has the ability to evade both efflux and ribosomal methylation types of resistance and therefore has an expanded spectrum compared to other tetracycline agents. Omadacycline is active against a number of multidrug-resistant bacteria, including macrolide and doxycycline-resistant Streptococcus pneumoniae, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus, and several enteric gram-negative bacilli. It also has activity against many nontuberculous mycobacterium (NTM) species. It is available both orally and intravenously, which allows for feasible switch therapy. This review will assess the antimicrobial activity, pharmacology, safety, and clinical efficacy of omadacycline and present the opinions of the authors on where to position omadacycline for clinical practice.

Acupuncture as an adjunctive therapy for sleep fragmentation in Parkinson's disease: a pilot study based on polysomnography.

This pilot study aims to assess the feasibility and preliminary effectiveness. of acupuncture as an adjunct therapy for improving sleep quality in patients with Parkinson's Disease (PD) who are experiencing fragmented sleep disorders. This pilot study recruited a small cohort of 11 patients diagnosed. With PD, each undergoing a structured 4-week acupuncture intervention comprising three sessions per week. Outcome measures included polysomnography (PSG) and the Pittsburgh Sleep Quality Index (PSQI), both of which were evaluated at baseline and following the completion of the 4-week acupuncture regimen. Post-intervention analysis showed trends toward improved sleep continuity with statistical significance in the sleep arousal index (p = 0.001), sleep arousal frequency (p = 0.001), and PSQI scores (p = 0.026) compared to baseline measurements. Importantly, no adverse events or complications were reported throughout the study period. The results indicate that acupuncture provides preliminary evidence supporting its use as a feasible adjunctive therapy for improving sleep quality in individuals with PD. Further research is required to evaluate the long-term efficacy of acupuncture and to examine its practicality and feasibility for integration into established PD management protocols.

Efficacy and safety of first-line PD-1/PD-L1 inhibitor in combination with CTLA-4 inhibitor in the treatment of patients with advanced non-small cell lung cancer: a systemic review and meta-analysis.

The combination of PD-1/PD-L1 inhibitor with CTLA-4 inhibitor for advanced non-small cell lung cancer(NSCLC) is presently a significant area of research, however its clinical application remains contentious. This meta-analysis aimed to assess the efficacy and safety of first-line PD-1/PD-L1 inhibitor in combination with CTLA-4 inhibitor (CP) in the treatment of patients with advanced NSCLC. A systemic search was conducted in four databases (PubMed, Cochrane library, Embase, and Web of Science) from their establishment until January 17, 2024, for randomized controlled trials that investigated the use of the first-line PD-1/PD-L1 inhibitor plus CTLA-4 inhibitor in patients with advanced NSCLC. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs) were subjected to meta-analyses. Totally 7 eligible randomized controlled trials including 4682 people were included. Two comparative analyses were performed: CP versus chemotherapy, CP versus PD-1/PD-L1 inhibitor (P). Compared with the chemotherapy group, CP improved OS (HR: 0.84, 95% CI: 0.75-0.94, p<0.05) but not PFS (HR: 0.94, 95%CI: 0.73-1.20, p = 0.63) or ORR (OR: 1.16, 95% CI: 0.79-1.71, p = 0.45). In terms of toxicity, CP had slightly fewer any AEs compared to chemotherapy (RR: 0.94, 95% CI: 0.91-0.97; p<0.05). Compared to the P group, there was no significant difference in OS (MD: -0,25, 95% CI: -2.47-1.98, p = 0.83), PFS (MD: -0.91, 95% CI: -3.19-1.36, p = 0.43), and ORR (OR:1.05, 95% CI. 0.80-1.36, p = 0.73). Subgroup analysis revealed that CP provided superior OS compared with P in patients with PD-L1 expression < 1%. CP was a feasible and safe first-line therapy for patients with advanced NSCLC. Specifically, CP may function as a therapeutic alternative for individuals with low or negative PD-L1 expression, resulting in enhanced long-term outcomes compared to chemotherapy or P. Further randomized controlled trials with prolonged follow-up periods are necessary to validate these results, particularly focusing on efficacy in patients with differing PD-L1 expression levels, to improve the stratified implementation of immunotherapy. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024621116, identifier CRD42024621116.

A new therapy for microcystic lymphatic malformations: the combination of intralesional laser thermolysis and percutaneous sclerotherapy.

Over the past few decades, percutaneous sclerotherapy has been proven to be efficacy in treating macrocystic lymphatic malformations (LMs). Unfortunately, there still remains challenging in the treatment of microcystic LMs given their size. We introduce the intralesional laser thermolysis (ILT) technique, a novel enhancement technique for the traditional percutaneous sclerotherapy in the treatment of microcystic LMs. A retrospective analysis of children with microcystic LMs treated using ILT combined with percutaneous sclerotherapy was done. All patients underwent clinically and cross-sectional imaging to assess response to treatment. Between January 2020 and April 2022, 16 consecutive patients (female/male ratio: 7:9; average age, 32.6months; range: 6months to 16years) with microcystic LMs received treatment with ILT combined with percutaneous sclerotherapy. A total of twenty-six sessions of combination therapy were performed, with a mean number of sessions per patient of 1.6 (±0.7), ranging from 1 to 3 sessions. The follow-up time ranged from 6 to 24months, with a mean of 15.8 (±6.3) months. Almost all patients showed significant improvement after the combination therapy. No major complications were observed. Minor complications included circumscribed skin blisters, postoperative non-infectious fever, transient skin edema, pigmentation, and slight depressions of localized skin. The treatment of intralesional laser thermolysis combined with traditional sclerotherapy is considered as a safe, feasible and effective therapy in treating microcystic LMs.

Major pathologic response predicts survival in resectable stage IIIA non-small cell lung cancer after neoadjuvant therapy.

Major pathologic response is more common in survival analyses than pathological complete response. Whether major pathologic response can predict survival of patients with resectable stage IIIA non-small cell lung cancer and whether neoadjuvant chemotherapy or immunochemotherapy affect the prognosis of patients remains questionable. Patients with resectable stage IIIA non-small cell lung cancer receiving neoadjuvant chemotherapy (≥2 cycles) with/without immunotherapy were enrolled and divided into two groups according to pathological response. Comparison between the two groups was through chi-square test. Univariate Cox regression analysis and log-rank test were made to identify predictive factors of overall survival and disease-free survival. Kaplan-Meier survival curves were constructed to evaluate the prognostic impact of these factors. Totally, 38 patients were enrolled. Significant difference was observed in overall survival (P = 0.005) and disease-free survival (P = 0.007) between patients with/without major pathologic response. For patients failing to reach major pathologic response, those who underwent ≥2 cycles of neoadjuvant therapy exhibited improved outcomes in overall survival (P = 0.021) and disease-free survival (P = 0.046). Notably, within this subgroup, patients receiving ≥ 2 cycles of neoadjuvant immunochemotherapy showed a trend towards better overall survival (P = 0.076) and disease-free survival (P = 0.062). Major pathologic response can predict survival of patients with resectable stage IIIA non-small cell lung cancer. For patients potentially not achieving major pathologic response after two cycles of neoadjuvant therapy, extended cycles of feasible neoadjuvant therapy are advisable for survival benefits.

Targeting the mevalonate pathway enhances the efficacy of 5-fluorouracil by regulating pyroptosis

The 5-fluorouracil (5-FU)-based chemotherapy regimen is a primary strategy for treating pancreatic cancer (PC). However, challenges related to 5-FU resistance persist. Investigating the mechanisms of 5-FU resistance and identifying a clinically viable therapeutic strategy are crucial for improving the prognosis of PC. Here, through clinical samples analysis, we found that the expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), the rate-limiting enzyme in mevalonate metabolism, is negatively correlated with the efficacy of 5-FU treatment. There is a significant correlation between HMGCR and the pyroptosis marker gasdermin D (GSDMD), and the HMGCR inhibitor simvastatin can significantly inhibit the activation of pyroptosis signaling. The exogenous addition of geranylgeranyl pyrophosphate (GGPP), a key metabolite of the mevalonate pathway, can significantly reduce sensitivity to 5-FU, and simvastatin combined with 5-FU demonstrates a strong synergistic effect. Furthermore, in organoid models and genetically engineered mice with spontaneous PC, the combination of simvastatin and 5-FU significantly inhibits tumor growth. In conclusion, our study reveals the critical role of the mevalonate pathway in 5-FU resistance and proposes a clinically feasible combination therapy strategy.

Lipid nanoparticle delivery of TALEN mRNA targeting LPA causes gene disruption and plasma lipoprotein(a) reduction in transgenic mice

Lipid nanoparticle delivery of TALEN mRNA targeting LPA causes gene disruption and plasma lipoprotein(a) reduction in transgenic mice

OGC SO14 - Management of Anastomotic Leaks after oesophagectomy for oesophageal cancer in the era of Endoscopic Vacuum Therapy

Abstract Background Anastomotic leak (AL) is a serious complication following oesophagectomy that occurs in 10-15% of patients. Endoscopic vacuum therapy (EVT) is a novel non-operative approach to managing AL that has become increasingly popular recently. However, little is known about EVT’s effectiveness in managing ALs compared to more established approaches. Method This was a retrospective review of consecutive AL management in a regional oesophageal cancer centre during two distinct time periods: prior to (group 1, 2014-2018) and following (group 2, 2018-2023) the introduction of EVT. 66 patients met the inclusion criteria. Patients were further classified according to size and type of leak, degree of mediastinal soiling and degree of sepsis. Primary endpoints were treatment success, 90-day mortality, and long-term preservation of gastrointestinal continuity. Secondary endpoints were the length of hospital stay (LOS) and re-interventions during the first postoperative year. Results 80.3% of patients (14 in group 1, 40 in group 2) had less than 1cm AL defect with present sepsis and a small mediastinal cavity. In group 1, 12 were treated successfully conservatively, and 2 (14.2%) had T-tube insertion. In group 2, 20 (50%) had conservative management and 19 (47.5%) had Esosponge insertion. The success rate was 95% and 94.7%, respectively. In bigger ALs (&amp;gt;1cm defect with severe sepsis), all patients in group I were treated with thoracotomy with a success rate of 75%, whereas in group 2, 60% were treated with Esosponge insertion with a success rate of 83.3%. Conclusion EVT is a safe and feasible therapy option. It appears to improve outcomes in septic patients with small ALs and potentially reduces the need for high-risk revisional operations.

Efficacy and safety of allogeneic platelet-rich plasma in chronic wound treatment: a meta-analysis of randomized controlled trials

Allogeneic platelet-rich plasma (al-PRP) is gaining attention in clinical practice for treating chronic refractory wounds, though research results remain controversial. To assess the clinical efficacy of al-PRP for chronic refractory wounds. Databases including PubMed, Cochrane Library, Embase, CNKI, SinoMed, VIP, and WFPD were searched for randomized controlled trials comparing al-PRP with conventional treatments up to October 2023. Two researchers independently screened studies, extracted data, and assessed quality. Statistical analysis was conducted using RevMan 5.4, and potential publication bias was assessed and corrected using funnel plots and Egger’s test. Twelve studies with 717 cases were included. Meta-analysis showed al-PRP significantly improved outcomes compared to non-al-PRP treatments: increased healing rate (RR 2.72, 95% CI 1.77–4.19, p < 0.00001), shortened healing time (SMD − 1.03, 95% CI -1.31 to -0.75, p < 0.00001), improved efficacy rate (RR 1.19, 95% CI 1.10–1.28, p < 0.00001), increased wound shrinkage (MD 35.65%, 95% CI 21.65–49.64, p < 0.00001), and reduced hospital stays (MD -2.62, 95% CI -4.35 to -0.90, p = 0.003). Al-PRP is a feasible, effective, and safe biological therapy for chronic refractory wounds.Trial registration: PROSPERO Identifier CRD42022374920.

Effectiveness of a 12-week combining tai chi and yoga program on pulmonary function and functional fitness in COPD patients

Effectiveness of a 12-week combining tai chi and yoga program on pulmonary function and functional fitness in COPD patients

Introducing a new social cognition online therapy: SoCoBo

ABSTRACT Integrating technology-based therapies into existing treatment approaches has proven useful in the endeavour to improve impaired social cognition in patients with neurological diseases. To this end, we present a novel online-based therapy programme for the treatment of impairments of social cognition (“SoCoBo”), particularly tailored for patients with acquired brain injuries (ABIs). This study was designed to investigate the online therapy's feasibility including processing time and acceptability in a healthy older sample as, according to previous studies, older individuals show subtle impairments of social cognition. Between 50 and 52 participants (depending on outcome measures) underwent pre–post assessments, completed one out of three therapy modules (emotion recognition, perspective taking, social problem-solving) over a period of four weeks (four sessions per week) and evaluated the therapy concerning feasibility, acceptability and content aspects with a newly developed questionnaire. All modules showed comparable ratings on a low to moderate level in terms of feasibility, acceptability and content aspects, which seems plausible due to the sample under investigation. Processing time of the three modules was comparable for psychoeducation (mean 17.45 min) and training sessions (mean 21.91 min). The results provided important indications for necessary adjustments regarding a subsequently completed randomized controlled trial involving patients with ABIs.

Remote ischemic post-conditioning for neonatal encephalopathy: a safety and feasibility trial.

Despite implementation of therapeutic hypothermia (TH) for infants with neonatal encephalopathy (NE), a significant proportion of infants suffer neurodevelopmental impairment (NDI). Remote ischemic conditioning (RIC) is a proposed neuroprotective maneuver that has been studied in adults with brain injury, but it has not been previously investigated in infants with NE. We performed a prospective, randomized, safety and dose escalation study in 32 neonates with NE. Four cohorts of consecutive patients were randomized to RIC therapy, including four cycles of limb ischemia and reperfusion on progressive days of TH, or sham. Clinical, biochemical, and safety outcomes were monitored in both groups. All patients received the designated RIC therapy without interruption or delay. RIC was not associated with increased pain, vascular, cutaneous, muscular, or neural safety events. There was no difference in the incidence of seizures, brain injury, or mortality between the two groups with the escalation of RIC dose and frequency. We found that RIC is a safe and feasible adjunctive therapy for neonates with NE undergoing TH. This pilot study establishes critical safety and feasibility data that are necessary for the design of future studies to investigate the potential efficacy of RIC to reduce NDI. Remote ischemic conditioning (RIC) is a possible neuroprotective intervention in infants with hypoxic-ischemic encephalopathy (HIE). RIC can be administered concurrently with therapeutic hypothermia without any notable adverse events. Future studies will need to address potential efficacy of RIC to improve neurodevelopmental outcomes, as well as consider the ideal temporal window and dose for RIC in this patient population.