GM-CSF: Orchestrating the Pulmonary Response to Infection

This review summarizes the structure and function of the alveolar unit, comprised of alveolar macrophage and epithelial cell types that work in tandem to respond to infection. Granulocyte-macrophage colony-stimulating factor (GM-CSF) helps to maintain the alveolar epithelium and pulmonary immune system under physiological conditions and plays a critical role in restoring homeostasis under pathologic conditions, including infection. Given the emergence of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and global spread of coronavirus disease 2019 (COVID-19), with subsequent acute respiratory distress syndrome, understanding basic lung physiology in infectious diseases is especially warranted. This review summarizes clinical and preclinical data for GM-CSF in respiratory infections, and the rationale for sargramostim (yeast-derived recombinant human [rhu] GM-CSF) as adjunctive treatment for COVID-19 and other pulmonary infectious diseases.

Selective 5HT3 antagonists and sensory processing: a systematic review

Ondansetron is a selective serotonin (5HT3) receptor antagonist that is under evaluation as an adjunctive treatment for schizophrenia, and a novel treatment for hallucinations in Parkinson’s disease. Ondansetron reverses sensory gating deficits and improves visuoperceptual processing in animal models of psychosis, but it is unclear to what extent preclinical findings have been replicated in humans. We systematically reviewed human studies that evaluated the effects of ondansetron and other 5HT3 receptor antagonists on sensory gating deficits or sensory processing. Of 11 eligible studies, eight included patients with schizophrenia who were chronically stable on antipsychotic medication; five measured sensory gating using the P50 suppression response to a repeated auditory stimulus; others included tests of visuoperceptual function. Three studies in healthy participants included tests of visuoperceptual and sensorimotor function. A consistent and robust finding (five studies) was that ondansetron and tropisetron (5HT3 antagonist and α7-nicotinic receptor partial agonist) improved sensory gating in patients with schizophrenia. Tropisetron also improved sustained visual attention in non-smoking patients. There was inconsistent evidence of the effects of 5HT3 antagonists on other measures of sensory processing, but interpretation was limited by the small number of studies, methodological heterogeneity and the potential confounding effects of concomitant medication in patients. Despite these limitations, we found strong evidence that selective 5HT3 antagonists (with or without direct α7-nicotinic partial agonist effects) improved sensory gating. Future studies should investigate how this relates to potential improvement in neurocognitive symptoms in antipsychotic naive patients with prodromal or milder symptoms, in order to understand the clinical implications.

Chinese Medicine as an Adjunctive Treatment for Gastric Cancer: Methodological Investigation of meta-Analyses and Evidence Map

Background: Many meta-analyses (MAs) on Chinese medicine (CM) as an adjunctive treatment for gastric cancer have been published in recent years. However, the pooled evidence reported in MAs and their methodological quality remain unknown. Therefore, we designed a study to comprehensively evaluate and summarize the current evidence of CMs for gastric cancer in published MAs.Methods: A systematic search on MAs published in English from inception to 1st September 2021 was conducted in PubMed and Embase. The AMSTAR-2 tool was used to evaluate the methodological quality of the included MAs, and the results of the quality assessment were visualized using the evidence mapping method. Stata 17/SE was used for statistical analysis (Registration number: INPLASY202190005).Results: A total of 20 MAs (16 pairwise and 4 network MAs) were included from 118 records. These MAs were published in 14 journals from 2013 to 2021, with the number of patients and trials ranging from 688 to 6,857, and from 10 to 85, respectively. A large number of CMs (e.g., AiDi, FuFangKuShen, and HuaChanSu) in combination with chemotherapy for gastric cancer were identified among the included MAs. According to the pooled results reported in MAs, when compared to chemotherapy alone, CMs in combination with chemotherapy not only improve various outcomes on efficacy (e.g., objective response rate, quality of life) but also reduce various adverse reactions (e.g., leucopenia, nausea and vomiting). Only 2 MAs were low in terms of the overall methodological quality, while the other 18 MAs were all critically low. The methodology was required to be advanced significantly, mainly involving: study protocol and registration, explanation for the inclusion of study design, list of excluded studies with justifications, adequate details of included studies, reporting on funding sources of primary studies, and evaluation of the potential impact of risk of bias. In addition, MAs that received funds support (β = 2.68; 95%CI: 0.40 to 4.96; p = 0.024) or were published in journals with higher impact factor (β = 2.81; 95%CI: 0.69 to 4.92; p = 0.012) had a higher score on the overall methodological quality in the univariate analysis, but the results were not statistically significant according to the multivariate analysis.Conclusion: Combining CMs with chemotherapy can potentially improve clinical outcomes and reduce the relevant adverse effects in patients with gastric cancer. However, the methodological quality of relevant MAs requires significant improvement, and the current evidence needs to be validated through multinational trials that are well-designed and have a large sample size.

Association of Circulating Magnesium Levels in Patients With Alzheimer's Disease From 1991 to 2021: A Systematic Review and Meta-Analysis

Alzheimer's disease (AD) remains a medical and social challenge worldwide. Magnesium (Mg) is one of the most frequently evaluated essential minerals with diverse biological functions in human body. However, the association between circulating Mg levels and AD remains controversial. We conducted a meta-analysis of 21 studies published between 1991 and 2021 to determine whether the Mg levels in the blood and cerebrospinal fluid (CSF) are abnormal in AD. Literatures were searched in PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang Data without language limitations. A pooled subject sample including 1,112 AD patients and 1,001 healthy controls (HCs) was available to assess Mg levels in serum and plasma; 284 AD patients and 117 HCs were included for Mg levels in CSF. It was found that serum and plasma levels of Mg were significantly reduced in AD patients compared with HCs (standardized mean difference [SMD] = −0.89; 95% confidence interval [CI] [−1.36, −0.43]; P = 0.000). There was statistically non-significant for Mg level in CSF between AD and HCs, whereas a decreased tendency were detected (SMD = −0.16; 95% CI [−0.50, 0.18]; P = 0.364). .In addition, when we analyzed the Mg levels of serum, plasma and CSF together, the circulating Mg levels in AD patients was significantly lower (SMD = −0.74, 95% CI [−1.13; −0.35]; P = 0.000). These results indicate that Mg deficiency may be a risk factor of AD and Mg supplementation may be a potentially valuable adjunctive treatment for AD.Systematic Review Registration:www.crd.york.ac.uk/PROSPERO/, registration number CRD42021254557.

Role of Probiotics in the Management of COVID-19: A Computational Perspective

Coronavirus disease 2019 (COVID-19) was declared a pandemic at the beginning of 2020, causing millions of deaths worldwide. Millions of vaccine doses have been administered worldwide; however, outbreaks continue. Probiotics are known to restore a stable gut microbiota by regulating innate and adaptive immunity within the gut, demonstrating the possibility that they may be used to combat COVID-19 because of several pieces of evidence suggesting that COVID-19 has an adverse impact on gut microbiota dysbiosis. Thus, probiotics and their metabolites with known antiviral properties may be used as an adjunctive treatment to combat COVID-19. Several clinical trials have revealed the efficacy of probiotics and their metabolites in treating patients with SARS-CoV-2. However, its molecular mechanism has not been unraveled. The availability of abundant data resources and computational methods has significantly changed research finding molecular insights between probiotics and COVID-19. This review highlights computational approaches involving microbiome-based approaches and ensemble-driven docking approaches, as well as a case study proving the effects of probiotic metabolites on SARS-CoV-2.

Aflibercept as Adjunctive Treatment for Filtration Surgery in Neovascular Glaucoma

Objective: To investigate intravitreal aflibercept (IVA) injection as an adjunctive treatment to trabeculectomy with mitomycin C (TMC) and panretinal photocoagulation (PRP) for neovascular glaucoma (NVG).Materials and Methods: PRP and IVA (2 mg/0.05 ml) injection were given, and TMC was performed within 2weeks after IVA. Additional PRP, laser suture lysis, subconjunctival 5-fluorouracil injection, and bleb needlingwere performed after TMC if indicated. Best corrected visual acuity (BCVA), intraocular pressure (IOP), surgicalcomplications, and number of anti-glaucoma medications were collected.Results: Five eyes from 5 consecutive patients were included. Two eyes had proliferative diabetic retinopathy (PDR), 2 central retinal vein occlusion, and 1 ocular ischemic syndrome (OIS) (mean initial IOP: 46.8±6.8 mmHg). NVI regression occurred in one eye after PRP alone, and in one eye after PRP and IVA resulting in a good IOP control with topical medical therapy. The other 3 underwent TMC. The preoperative IOP was 34 (OIS), 54 (PDR), and 50 (PDR) mmHg. The 3-month postoperative IOP decreased to 8, 8, and 4 mmHg, respectively, and to 21, 10, and 6 mmHg, respectively, at the last visit. Only the one OIS eye required postoperative topical IOP-lowering medications. Final BCVA was improved, unchanged, and decreased in 2, 2, and 1 eye, respectively. No intraoperative/postoperative complications or NVI recurrence were observed (mean follow-up: 10.7 months).Conclusion: Intravitreal aflibercept was shown to be a potentially effective additional treatment to PRP and TMC in patients with NVG.

Occipital cranioplasty using customized titanium prosthesis yields successful outcome in association with foramen magnum decompression in dogs suffering by Chiari-like malformation

OBJECTIVE To describe the use of a customized 3–D-printed titanium prosthesis as adjunctive treatment for foramen magnum decompression (FMD) in dogs with Chiari-like malformation (CM) and syringomyelia (SM). ANIMALS 8 dogs with clinical signs and MRI findings of CM-SM. PROCEDURES 3-D reconstruction of CT images of the head was used to simulate an occipital craniectomy and design the prosthesis. FMD was performed, and the prosthesis was implanted. Follow-up was performed 1, 6, and 12 months later, and clinical status was scored. Repeated MRI images were compared to identify changes involving the neural structures, particularly the syrinx. RESULTS All prostheses were easily positioned based on the preoperative 3-D models, with no complications. At 12 months after surgery, 3 dogs were free of previous medications, 4 were still receiving steroid medications but at lower doses, and 1 was occasionally receiving acupuncture. MRI of 5 dogs 6 to 20 months after surgery revealed resolution of SM (n = 1), reduced size of SM (3), or worse SM (1). All dogs showed an increase in size of the caudal cranial fossa. Dogs with a longer presurgical duration of the clinical signs and wider syrinx generally had worse outcomes than other dogs. CLINICAL RELEVANCE Findings suggested that use of customized 3–D-printed titanium prosthesis and associated FMD can represent an adjunctive option to medically treated dogs with CM-SM. Although the small number of cases precludes definitive conclusions, early surgical treatment, particularly in dogs with a small syrinx, could ensure better long-term outcomes, as previously suggested.

The Role of the Gut Microbiota in the Development and Progression of Major Depressive and Bipolar Disorder

A growing number of studies in rodents indicate a connection between the intestinal microbiota and the brain, but comprehensive human data is scarce. Here, we systematically reviewed human studies examining the connection between the intestinal microbiota and major depressive and bipolar disorder. In this review we discuss various changes in bacterial abundance, particularly on low taxonomic levels, in terms of a connection with the pathophysiology of major depressive and bipolar disorder, their use as a diagnostic and treatment response parameter, their health-promoting potential, as well as novel adjunctive treatment options. The diversity of the intestinal microbiota is mostly decreased in depressed subjects. A consistent elevation of phylum Actinobacteria, family Bifidobacteriaceae, and genus Bacteroides, and a reduction of family Ruminococcaceae, genus Faecalibacterium, and genus Roseburia was reported. Probiotics containing Bifidobacterium and/or Lactobacillus spp. seemed to improve depressive symptoms, and novel approaches with different probiotics and synbiotics showed promising results. Comparing twin studies, we report here that already with an elevated risk of developing depression, microbial changes towards a “depression-like” microbiota were found. Overall, these findings highlight the importance of the microbiota and the necessity for a better understanding of its changes contributing to depressive symptoms, potentially leading to new approaches to alleviate depressive symptoms via alterations of the gut microbiota.