Efficacy of photobiomodulation in the management of tinnitus: A systematic review of randomized control trials

There is a controversy in regards to the efficacy of photobiomodulation (PBM) in the management of tinnitus. The aim was to systematically review randomized controlled trials (RCTs) that assessed the efficacy of PBM (low-level laser therapy) in the management of tinnitus. The focused question was “Is PBM effective in the management of tinnitus?”. Indexed databases were searched up to and including June 2020 using different combinations of the following key words: (a) laser; (b) diode; (c) low-level laser therapy; (d) photobiomodulation; (e) tinnitus; (f) medium-level laser; (g) photo-biomodulation; and (h) low-power laser; and RCTs performed on humans were included. Letters to the editor; case reports/series; commentaries; experimental studies and historic reviews were excluded. The risk of bias was assessed using the modified cochrane collaboration tool. The format of the current systematic review was personalized to summarize the appropriate information. Ten RCTs (2 single-blinded and 8 double-blinded) were included. One study reported 30% and 100% resolution of tinnitus using diode and Neodymium-doped Yttrium Aluminum Garnet lasers; respectively. One study reported that PBM was effective in relieving tinnitus for up to 3 months. Eight studies reported that PBM was ineffective in the management of chronic tinnitus. The risk of bias was high; medium and low in 4; 5 and 1 studies; respectively. The effectiveness of PBM in the management of tinnitus remains debatable. Further power-adjusted and well-designed RCTs with long-term follow-up are needed.     

Long-term prevention of bladder cancer progression by alpha1-oleate alone or in combination with chemotherapy

Bladder cancer is common and one of the most costly cancer forms, due to a lack of curative therapies. Recently, clinical safety and efficacy of the alpha1-oleate complex was demonstrated in a placebo-controlled study of nonmuscle invasive bladder cancer. Our study investigated if long-term therapeutic efficacy is improved by repeated treatment cycles and by combining alpha1-oleate with low-dose chemotherapy. Rapidly growing bladder tumors were treated by intravesical instillation of alpha1-oleate, Epirubicin or Mitomycin C alone or in combination. One treatment cycle arrested tumor growth, with a protective effect lasting at least 4 weeks in mice receiving 8.5 mM of alpha1-oleate alone or 1.7 mM of alpha-oleate combined with Epirubicin or Mitomycin C. Repeated treatment cycles extended protection, defined by a lack of bladder pathology and a virtual absence of bladder cancer-specific gene expression. Synergy with Epirubicin was detected at the lower alpha1-oleate concentration and in vitro, alpha1-oleate was shown to enhance the uptake and nuclear translocation of Epirubicin, by tumor cells. Effects at the chromatin level affecting cell proliferation were further suggested by reduced BrdU incorporation. In addition, alpha1-oleate triggered DNA fragmentation, defined by the TUNEL assay. The results suggest that bladder cancer development may be prevented long-term in the murine model, by alpha1-oleate alone or in combination with low-dose Epirubicin. In addition, the combination of alpha1-oleate and Epirubicin reduced the size of established tumors. Exploring these potent preventive and therapeutic effects will be of immediate interest in patients with bladder cancer.     

Dual-target inhibitors of bromodomain-containing protein 4 (BRD4) in cancer therapy: Current situation and future directions

Bromodomain-containing protein 4 (BRD4) is emerging as a therapeutic target that acts synergistically with other targets of small-molecule drugs in cancer. Therefore, the discovery of potential new dual-target inhibitors of BRD4 may be a promising strategy for cancer therapy. In this review, we highlight a series of strategies to design therapeutic dual-target inhibitors of BRD4 that focus on the synergistic functions of this protein. Drug combinations that exploit synthetic lethality, protein–protein interactions, functional complementarity, and blocking of resistance mechanisms could ultimately overcome the barriers inherent to the development of BRD4 inhibitors as future cancer drugs.     

The effect of massage therapy on pain after surgery: A comprehensive meta-analysis

BackgroundFindings on the usefulness of massage therapy (MT) in postoperative pain management are often inconsistent among studies.ObjectivesThis study’s aim is to conduct a meta-analysis of randomized controlled trials (RCT) to clarify the effects of massage therapy in the treatment of postoperative pain.MethodsThree databases (PubMed, Embase, and Cochrane Central Register of Controlled Trials) were searched for RCTs published from database inception through January 26, 2021. The primary outcome was pain relief. The quality of RCTs was appraised with the Cochrane Collaboration risk of bias tool. The random-effect model was used to calculate the effect sizes and standardized mean difference (SMD) with 95 % confidential intervals (CIs) as a summary effect. The heterogeneity test was conducted through I². Subgroup and sensitivity analyses were used to explore the source of heterogeneity. Possible publication bias was assessed using visual inspection of funnel plot asymmetry.ResultsThe analysis included 33 RCTs and showed that MT is effective in reducing postoperative pain (SMD, −1.32; 95 % CI, −2.01 to −0.63; p = 0.0002; I² = 98.67 %). A similar significant effect was found for both short (immediate assessment) and long terms (assessment performed 4–6 weeks after the MT). Remarkably, we found neither the duration per session nor the dose had an impact on the effect of MT and there seemed to be no difference in the effects of different MT types. In addition, MT seemed to be more effective for adults. Furthermore, MT had better analgesic effects on cesarean section and heart surgery than orthopedic surgery.LimitationsPublication bias is possible due to the inclusion of studies in English only. Additionally, the included studies were extremely heterogeneous. Double-blind research on MT is difficult to implement, and none of the included studies is double-blind. There was some heterogeneity and publication bias in the included studies. In addition, there is no uniform evaluation standard for the operation level of massage practitioners, which may lead to research implementation bias.ConclusionsMT is effective in reducing postoperative pain in both short and long terms.     

Top advances of the year: Hepatobiliary cancers

This commentary reviews top advances in hepatobiliary cancer research in 2021–2022, focusing on leveraging immunotherapeutics in combination with other therapies earlier in the disease course and targeted to patient's individualized biomarkers that may predict response or resistance to checkpoint inhibitors.