Effect of Laser and Energy-based Device Therapies to Minimize Surgical Scar Formation: A Systematic Review and Network Meta-analysis.

Utilization of lasers and energy-based devices for surgical scar minimization has been substantially evaluated in placebo-controlled trials. The aim of this study was to compare reported measures of efficacy of lasers and energy-based devices in clinical trials in preventing surgical scar formation in a systematic review and network meta-analyses. Five electronic databases, PubMed, Scopus, Embase, ClinicalTrials.gov, and the Cochrane Library, were searched to retrieve relevant articles. The search was limited to randomized controlled trials that reported on clinical outcomes of surgical scars with treatment initiation no later than 6 months after surgery and a follow-up period of at least 3 months. A total of 18 randomized controlled trials involving 482 participants and 671 postsurgical wounds were included in the network meta-analyses. The results showed that the most efficacious treatments were achieved using low-level laser therapy) (weighted mean difference -3.78; 95% confidence interval (95% CI) -6.32, -1.24) and pulsed dye laser (weighted mean difference -2.46; 95% CI -4.53, -0.38). Nevertheless, low-level laser therapy and pulsed dye laser demonstrated comparable outcomes in surgical scar minimization (weighted mean difference -1.32, 95% CI -3.53, 0.89). The findings of this network meta-analyses suggest that low-level laser therapy and pulsed dye laser are both effective treatments for minimization of scar formation following primary closure of surgical wounds with comparable treatment outcomes.

Randomized controlled trial and cost-effectiveness analysis: Comparing chlorhexidine scrub, ZnO-nanoparticle socks, and their combination in pitted keratolysis treatment.

A cost-effective treatment for pitted keratolysis (PK) is the use of 4% chlorhexidine scrub. Zinc oxide nanoparticle (ZnO-NP)-coated socks have also shown efficacy in PK prevention. In this study, we aimed to assess the cost-effectiveness and safety of combined 4% chlorhexidine scrub and ZnO-NP-coated sock treatment compared to monotherapy. This randomized, controlled trial included 60 male security guards and hospital porters aged ≥18 with PK. Participants were randomly assigned to one of three treatment groups: 4% chlorhexidine scrub, ZnO-NP-coated socks, or combination therapy. Treatment outcomes were evaluated after 4 weeks. Incremental cost-effectiveness ratios (ICERs) were calculated using cost-utility analysis. The greatest reduction in visual analog scale scores for foot odor was observed in the combination therapy group, but it was nonsignificant (P = 0.186). Clinical improvement was observed across all groups. The cost-utility analysis revealed that chlorhexidine scrub and regular socks were the least expensive options. The placebo and ZnO-NP-coated sock group had an ICER of US $31 082/quality-adjusted life years (QALYs) gain, while the combination therapy gained US $45 105/QALYs compared to the chlorhexidine scrub and regular sock group. Based on our findings, for the treatment of PK, 4% chlorhexidine scrub remains the most cost-effective choice.

Immune-related adverse effects of checkpoint immunotherapy and implications for the treatment of patients with cancer and autoimmune diseases.

During the past decade, there has been a revolution in cancer therapeutics by the emergence of antibody-based immunotherapies that modulate immune responses against tumors. These therapies have offered treatment options to patients who are no longer responding to classic anti-cancer therapies. By blocking inhibitory signals mediated by surface receptors that are naturally upregulated during activation of antigen-presenting cells (APC) and T cells, predominantly PD-1 and its ligand PD-L1, as well as CTLA-4, such blocking agents have revolutionized cancer treatment. However, breaking these inhibitory signals cannot be selectively targeted to the tumor microenvironment (TME). Since the physiologic role of these inhibitory receptors, known as immune checkpoints (IC) is to maintain peripheral tolerance by preventing the activation of autoreactive immune cells, IC inhibitors (ICI) induce multiple types of immune-related adverse effects (irAEs). These irAEs, together with the natural properties of ICs as gatekeepers of self-tolerance, have precluded the use of ICI in patients with pre-existing autoimmune diseases (ADs). However, currently accumulating data indicates that ICI might be safely administered to such patients. In this review, we discuss mechanisms of well established and newly recognized irAEs and evolving knowledge from the application of ICI therapies in patients with cancer and pre-existing ADs.

SHP-2 and PD-1-SHP-2 signaling regulate myeloid cell differentiation and antitumor responses.

The inhibitory receptor PD-1 suppresses T cell activation by recruiting the phosphatase SHP-2. However, mice with a T-cell-specific deletion of SHP-2 do not have improved antitumor immunity. Here we showed that mice with conditional targeting of SHP-2 in myeloid cells, but not in T cells, had diminished tumor growth. RNA sequencing (RNA-seq) followed by gene set enrichment analysis indicated the presence of polymorphonuclear myeloid-derived suppressor cells and tumor-associated macrophages (TAMs) with enriched gene expression profiles of enhanced differentiation, activation and expression of immunostimulatory molecules. In mice with conditional targeting of PD-1 in myeloid cells, which also displayed diminished tumor growth, TAMs had gene expression profiles enriched for myeloid differentiation, activation and leukocyte-mediated immunity displaying >50% overlap with enriched profiles of SHP-2-deficient TAMs. In bone marrow, GM-CSF induced the phosphorylation of PD-1 and recruitment of PD-1-SHP-2 to the GM-CSF receptor. Deletion of SHP-2 or PD-1 enhanced GM-CSF-mediated phosphorylation of the transcription factors HOXA10 and IRF8, which regulate myeloid differentiation and monocytic-moDC lineage commitment, respectively. Thus, SHP-2 and PD-1-SHP-2 signaling restrained myelocyte differentiation resulting in a myeloid landscape that suppressed antitumor immunity.

The evolving role of tissue-resident memory T cells in infections and cancer.

Resident memory T cells (TRM) form a distinct type of T memory cells that stably resides in tissues. TRM form an integral part of the immune sensing network and have the ability to control local immune homeostasis and participate in immune responses mediated by pathogens, cancer, and possibly autoantigens during autoimmunity. TRM express residence gene signatures, functional properties of both memory and effector cells, and remarkable plasticity. TRM have a well-established role in pathogen immunity, whereas their role in antitumor immune responses and immunotherapy is currently evolving. As TRM form the most abundant T memory cell population in nonlymphoid tissues, they are attractive targets for therapeutic exploitation. Here, we provide a concise review of the development and physiological role of CD8+ TRM, their involvement in diseases, and their potential therapeutic exploitation.

Immune cellular components and signaling pathways in the tumor microenvironment.

During the past decade there has been a revolution in cancer therapeutics by the emergence of antibody-based and cell-based immunotherapies that modulate immune responses against tumors. These new therapies have extended and improved the therapeutic efficacy of chemo-radiotherapy and have offered treatment options to patients who are no longer responding to these classic anti-cancer treatments. Unfortunately, tumor eradication and long-lasting responses are observed in a small fraction of patients, whereas the majority of patients respond only transiently. These outcomes indicate that the maximum potential of immunotherapy has not been reached due to incomplete knowledge of the cellular and molecular mechanisms that guide the development of successful anti-tumor immunity and its failure. In this review, we discuss recent discoveries about the immune cellular composition of the tumor microenvironment (TME) and the role of key signaling mechanisms that compromise the function of immune cells leading to cancer immune escape.