Case Report: Addition of PD-1 Antibody Camrelizumab Overcame Resistance to Trastuzumab Plus Chemotherapy in a HER2-Positive, Metastatic Gallbladder Cancer Patient

HER2 amplification/overexpression is a common driver in a variety of cancers including gallbladder cancer (GBC). For patients with metastatic GBC, chemotherapy remains the standard of care with limited efficacy. The combination of HER2 antibody trastuzumab plus chemotherapy is the frontline treatment option for patients with HER2-positive breast cancer and gastric cancer. Recently, this regime also showed antitumor activity in HER2-positive GBC. However, resistance to this regime represents a clinical challenge. Camrelizumab is a novel PD-1 antibody approved for Hodgkin lymphoma and hepatocellular carcinoma in China. In this study, we presented a HER2-positive metastatic GBC patient who was refractory to trastuzumab plus chemotherapy but experienced significant clinical benefit after the addition of camrelizumab. Our case highlights the potential of immunotherapy in combination with HER2-targeted therapy in HER2-positive GBC. We also demonstrated that two immune-related adverse events (irAEs) associated with camrelizumab can be managed with an anti-VEGF agent apatinib. This case not only highlights the importance of irAE management in patients treated with camrelizumab, but also demonstrates the potential of PD-1 antibody plus trastuzumab in HER2-positive GBC patients who have developed resistance to chemotherapy and trastuzumab-based targeted therapy.

Effect of Nerve Training Technology on Apoptosis of Cartilage and Osteoblasts and Expression of Aggrecan Protein in Osteoporotic Arthritis

Arthritis and osteoporosis are two common disorders in the world, especially for the elder, but the current treatments have limited efficacy. Herein, we aimed to determine whether the novel technique, neurological training can alleviate osteoporosis complicated with arthritis in rat model. Thirty rats were assigned into normal group, model group, and treatment group (treated with forsythin and neurological training) (n = 10) followed by assessment of chondrocytes and osteoblasts using Mankin score, apoptosis by TUNEL and flow cytometry, and IL-1β, TNF-α, and Aggrecan levels. Apoptotic chondrocytes of treatment group (27.43±1.34) was lower than model group (p < 0.05), whereas amount of osteoblast was increased upon forsythin and neurological training, with lower Mankin’s score (6.38±0.76). Besides, the content of IL-1β and TNF-α of treatment group was significantly lower but Aggrecan mRNA and protein expression was significantly higher. In conclusion, neurological training could protect and alleviate osteoporosis complicated with arthritis.

Novel urinary markers: taurine, dopamine and L-fucose levels in predicting neonatal seizures

Introduction and Aim: Neonatal seizure is an age specific neurological emergency. Their unique pathophysiological mechanism has become subject of interest for many research studies. The recurrence risk for seizures is high during neonatal period and currently used treatment strategies have limited efficacy in preventing it. From past decades although the treatment has not changed, there is a gradual progress in various mechanisms that are involved in generation of seizures and their response to anti-epileptics. With the emergence of new biochemical parameters for risk assessment in patients with seizures, there is a strong need for their comparative evaluation in order to evaluate their potential clinical application. So, this study was carried out to compare the urine levels of taurine, dopamine and fucose in assessing their role in mechanism of seizure. Materials and Methods: After obtaining ethical approval and consent from parents total 43 neonates, urine taurine, dopamine and fucose were measured in 24 cases of seizures and 19 apparently healthy normal controls. Dopamine and Taurine were measured using ELISA and L-fucose by Dische and Shettles method. Results: The median level of urine fucose was significantly higher in male neonates, taurine was significantly decreased in cases compared to that of controls. Males had higher preponderance to develop seizures. The median levels of urine dopamine were high in cases compared to controls but has not showed any significance. Conclusion: Amino acid like taurine, carbohydrate moiety like fucose and a neuromodulator like dopamine may have a mechanistic role in development of seizures in neonatal period.

An approach to treatment modalities of keloids: a comparative study

<p class="abstract"><strong>Background:</strong> In spite of the presence of such an array of treatment modalities, none of these can be claimed to be an ideal treatment option as most of them have limited efficacy, significant side effects or increased chances of recurrence. Hence the study was undertaken to search an ideal treatment for keloids which is safe, effective, and with low rate of recurrence.</p><p class="abstract"><strong>Methods:</strong> Total of 200 patients were recruited out of which only 160 patients were included in study. The patients were divided into three groups and administered with different modes of treatment. Patients in all the groups were followed up at 3 weekly intervals for evaluation of response. At the end of the study, the data was compiled and analysed using appropriate statistical tests.<strong></strong></p><p class="abstract"><strong>Results:</strong> In only 32 patients completed study in group 1, 2 and 3 respectively. Group 1, 2 and 3 were more or less equally efficacious with clearance rate. Complete clearance was seen in 24 patients in group 1 patients, in group 2 there were 22 patients with complete clearance and in group 3 there were 24 patients.</p><p class="abstract"><strong>Conclusions:</strong> Intralesional triamcinolone acetonide, intralesional triamcinolone acetonide with hyaluronidase and intralesional radiofrequency with intralesional triamcinolone acetonide are almost equally effective modalities for the treatment of keloids. But, intralesional triamcinolone acetonide with hyaluronidase fares better than other two as far as safety is concerned with least side effects.</p><p class="after-h2"> </p>

Updated picture of SARS-CoV-2 variants and mutations

The worldwide burden of coronavirus disease 2019 (COVID-19) is still unremittingly prosecuting, with nearly 300 million infections and over 5.3 million deaths recorded so far since the origin of the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) pandemic at the end of the year 2019. The fight against this new highly virulent beta coronavirus appears one of the most strenuous and long challenges that humanity has ever faced, since a definitive treatment has not been identified so far. The adoption of potentially useful physical preventive measures such as lockdowns, social distancing and face masking seems only partially effective for mitigating viral spread, though efficacy and continuation of such measures on the long term is questionable, due to many social and economic reasons. Many COVID-19 vaccines have been developed and are now widely used, though their effectiveness is challenged by several aspects such as low uptake and limited efficacy in some specific populations, as well as by continuous emergence of new mutations in the SARS-CoV-2 genome, accompanying the origin and spread of new variants, which in turn may contribute to further decrease the effectiveness of current vaccines and treatments. This article is hence aimed to provide an updated picture of SARS-CoV-2 variants and mutations that have emerged from November 2019 to present time (i.e., early December 2021).

Curcumin May Prevent Basement Membrane Disassembly by Matrix Metalloproteinases and Progression of the Bladder Cancer

Authors present a review of crucial mechanisms contributing to the invasion of the basement membrane (BM) of the urothelium by cancer cells and to the progression of bladder cancer (BC). The breeching of the urothelial BM, facilitated by an aberrant activation of matrix metalloproteinases (MMP) is particularly perilous. Inhibition of activation of these proteinases constitutes a logic opportunity to restrain progression. Because of limited efficacy of current therapeutic methods, the search for the development of alternative approaches constitutes “the hot spot” of modern oncology. Recent studies revealed significant anticancer potential of natural phytochemicals. Especially, curcumin has emerged as a one of the most promising phytochemicals and showed its efficacy in several human malignancies. Therefore, this article addresses experimental and clinical data indicating multi-directional inhibitory effect of curcumin on the growth of bladder cancer. We particularly concentrate on the mechanisms, by which curcumin inhibits the MMP’s activities, thereby securing BM integrity and alleviating the eventual cancer invasion into the bladder muscles. Authors review the recently accumulating data, that curcumin constitutes a potent factor contributing to the more effective treatment of the bladder cancer.

Preliminary Evidence of the Efficacy of Nitric Acid Treatment in Onychomycosis

Onychomycosis is the main cause of toenail disorders and is produced by a fungal infection. It is becoming more prevalent because of new lifestyles and immunosuppression statuses. The therapeutic approach to onychomycosis is under considerable study because of the lengthy treatments that require strong patient commitment, the limited efficacy of treatments, the inclusion of active substances that can be hepatotoxic and cause pharmacological interactions, and/or the questionable efficacy of treatments due to a lack of clinical trials. This study responds to the demand for rapid treatment with minimal pharmacological interactions. Methods: The efficacy of nitric acid 60% treatment in patients with onychomycosis was monitored and studied. The antifungal efficacy of nitric acid was measured by microbiological culture before and after treatment and the clinical evolution of nail dystrophy was quantitatively measured by monitoring with the Onychomycosis Severity Index (OSI). Results: The results show that, with the protocol used, nitric acid 60% painlessly cured 40% (microbiologic cure) of the cases treated, and in all cases, clinical improvement was observed (p = 0.011). Conclusions: The treatment with nitric acid 60% is as efficient as conventional treatments, requires less patient compliance of the treatment and produces no pharmacological interactions, providing alternative treatment in the case of hepatotoxicity.

Technological prospecting of music therapy in Alzheimer's disease

Alzheimer's disease (AD) is characterized by cognitive impairment and progressive memory loss and drug treatments have limited efficacy. Thus, non-pharmacological interventions, such as music therapy, have shown to be promising as supporting pharmacological treatment and, therefore, may arouse commercial interest regarding the development of this type of product. Thus, this study aims to carry out a patentometric survey on patent registrations with music therapy in the treatment of AD. A systematic search was carried out from 2000 to 2020 on the Orbti-Questel website, searching for documents referring to music therapies in AD. The terms “Alzheimer music methodology active therapy” and “Alzheimer music methodology passive therapy” were used. After searching, reading, and excluding duplicate results, we found four patent families referring to music therapy in AD and all were selected as a result, which was considered little compared to the number of studies published on the subject.

Identifying Targets for Interventions to Increase Earplug Use in Noisy Recreational Settings: A Qualitative Interview Study

Earplugs can reduce the risk of hearing loss and tinnitus. However, earplug use during noisy recreational activities is uncommon, and methods for increasing uptake and regular use have had limited efficacy. The aim of the present study was to examine barriers and enablers of ever-performers (e.g., people who have used earplugs) and never-performers (e.g., people who have not used earplugs) to identify targets to inform the content of interventions to increase uptake and regular use of earplugs in recreational settings. The Capabilities, Opportunities, and Motivations model of Behaviour (COM-B) informed the outline for 20 semi-structured telephone interviews (ever-performers, N = 8, age range = 20–45 years; never-performers, N = 12; age range = 20–50 years). Thematic analysis was used to identify barriers and enablers to earplug use, which were mapped onto the Theoretical Domains Framework (TDF). Six key domains of the TDF were identified. Ever-performers described being more exposed to ‘social influences’ (e.g., facilitators such as friends/peers) and were more positive than never-performers concerning ‘beliefs about consequences’ (e.g., earplug protection outweighs any negative effects on listening/communication). Involvement of ‘emotion’ (e.g., fear of losing ability to listen to music) and ‘reinforcement’ tactics (e.g., creating habits/routines) were discussed by ever-performers, but were not mentioned by never-performers. Both groups reported lack of ‘environmental context and resources’ (e.g., prompts and cues), and their own ‘memory, attention, and decision processes’ (e.g., deciding when to use earplugs) as barriers to earplug use. The present research identifies the variables that would need to change in order to increase earplug uptake and use in recreational settings among ever-performers and never-performers. Further work is required to translate these findings into testable interventions by selecting appropriate intervention functions (e.g., modelling), policy categories (e.g., communication/marketing), behaviour change techniques (e.g., demonstration of behaviour), and mode of delivery (e.g., face-to-face).