Rituximab treatment for systemic sclerosis-associated interstitial lung disease: a case series of 13 patients.

BACKGROUND: Systemic sclerosis (SSc) associated interstitial lung disease (ILD) is a common complication of SSc, with a high mortality, despite current available treatments. Rituximab has shown some promising, although varied, results for the treatment of SSc-ILD. AIMS: To determine whether rituximab stabilised or improved pulmonary function at 12 months, in patients with SSc-ILD. METHODS: A retrospective analysis of patients with SSc-ILD who progressed despite conventional therapy and received rituximab between 2008 and 2019 was performed at two tertiary centres. Baseline percentage forced vital capacity (FVC) and percentage diffusing capacity of carbon monoxide (DLCO) were compared with 1-year post the first dose of rituximab. Mean and median change in FVC (%) and DLCO (%) were calculated. For those with available data, the FVC (%) and DLCO (%) 2 years and 1 year prior to rituximab were compared with the change 12-months post-rituximab. RESULTS: Thirteen patients were included in the analysis. All patients demonstrated stability in their pulmonary function testing at 1-year post-rituximab. The mean FVC (%) was 57.18 (±16.93 standard deviation (SD)) prior to rituximab and 59.75 (±18.83 SD) 12-month post-rituximab, demonstrating an increase of 2.57 (±4.70 SD; P-value 0.07). The mean DLCO (%) increased from 37.10 (±18.41 SD) prior to rituximab to 38.03 (±19.83) post-rituximab. The mean change in DLCO (%) was 0.93 (±5.05 SD; P-value 0.53). In the 2 years preceding rituximab, the mean FVC (%) and DLCO (%) declined by 9.25 and 9.66 respectively. CONCLUSION: This case series suggests that rituximab might stabilise pulmonary function tests, and delay deterioration in patients with progressive SSc-ILD. These findings add to the growing body of evidence suggesting a role for rituximab in the treatment of SSc-ILD.

Hymenolepis diminuta-based helminth therapy in C3(1)-TAg mice does not alter breast tumor onset or progression.

BACKGROUND AND OBJECTIVES: An individual's risk of breast cancer is profoundly affected by evolutionary mismatch. Mismatches in Western society known to increase the risk of breast cancer include a sedentary lifestyle and reproductive factors. Biota alteration, characterized by a loss of biodiversity from the ecosystem of the human body as a result of Western society, is a mismatch known to increase the risk of a variety of inflammation-related diseases, including colitis-associated colon cancer. However, the effect of biota alteration on breast cancer has not been evaluated. METHODOLOGY: In this study, we utilized the C3(1)-TAg mouse model of breast cancer to evaluate the role of biota alteration in the development of breast cancer. This model has been used to recapitulate the role of exercise and pregnancy in reducing the risk of breast cancer. C3(1)-TAg mice were treated with Hymenolepis diminuta, a benign helminth that has been shown to reverse the effects of biota alteration in animal models. RESULTS: No effect of the helminth H. diminuta was observed. Neither the latency nor tumor growth was affected by the therapy, and no significant effects on tumor transcriptome were observed based on RNAseq analysis. CONCLUSIONS AND IMPLICATIONS: These findings suggest that biota alteration, although known to affect a variety of Western-associated diseases, might not be a significant factor in the high rate of breast cancer observed in Western societies. LAY SUMMARY: An almost complete loss of intestinal worms in high-income countries has led to increases in allergic disorders, autoimmune conditions, and perhaps colon cancer. However, in this study, results using laboratory mice suggest that loss of intestinal worms might not be associated with breast cancer.

Murine model of oropharyngeal gastric fluid aspiration-A new assessment method for intrapulmonary liquid distribution using digital pixel calculation.

AIM OF THE STUDY: The aim of this study was to investigate a new method for visualization and quantification of intrapulmonary liquid distribution after oropharyngeal gastric fluid aspiration in mice. MATERIAL AND METHODS: Eleven mice received oropharyngeal aspiration with a gastric fluid, India ink, and saline solution. Digital imaging and pixel calculation were used to analyze intrapulmonary fluid distribution selectively. RESULTS: Digital pixel analysis and orophanryngeal aspiration are both safe techniques in mice and deliver reproducible/valid results. Analysis revealed an average aspirate distribution of 86.8% of the total lung area. The proportional amount of the left lung was significantly greater than that of the right lung (P = 0.023). The lobe with the lowest mean distribution was the right lower lobe (79.2% ± 4.4%). CONCLUSION: Digital pixel calculation is a reliable method for quantitative, macroscopic evaluation of fluid distribution in the lung. This method is a useful tool for training purposes and it can be used to ensure interinvestigator reproducibility.

Biomedical device innovation methodology: applications in biophotonics.

The process of medical device innovation involves an iterative method that focuses on designing innovative, device-oriented solutions that address unmet clinical needs. This process has been applied to the field of biophotonics with many notable successes. Device innovation begins with identifying an unmet clinical need and evaluating this need through a variety of lenses, including currently existing solutions for the need, stakeholders who are interested in the need, and the market that will support an innovative solution. Only once the clinical need is understood in detail can the invention process begin. The ideation phase often involves multiple levels of brainstorming and prototyping with the aim of addressing technical and clinical questions early and in a cost-efficient manner. Once potential solutions are found, they are tested against a number of known translational factors, including intellectual property, regulatory, and reimbursement landscapes. Only when the solution matches the clinical need, the next phase of building a "to market" strategy should begin. Most aspects of the innovation process can be conducted relatively quickly and without significant capital expense. This white paper focuses on key points of the medical device innovation method and how the field of biophotonics has been applied within this framework to generate clinical and commercial success.

Immunization enhances the natural antibody repertoire.

The role of immunization in the production of antibodies directed against immunogens is widely appreciated in laboratory animals and in humans. However, the role of immunization in the development of "natural antibodies" has not been investigated. Natural antibodies are those antibodies present without known history of infection or immunization, and react to a wide range of targets, including "cryptic" self-antigens that are exposed upon cell death. In this study, the ability of immunization to elicit the production of natural antibodies in laboratory rats was evaluated. Laboratory rats were immunized with a series of injections using peanut extracts (a common allergen), a high molecular weight protein conjugated to hapten (FITC-KLH), and a carbohydrate conjugated to hapten (DNP-Ficall). Significantly greater binding of antibodies from immunized animals compared to controls was observed to numerous autologous organ extracts (brain, kidney, liver, lung, prostate, and spleen) for both IgM and IgG, although the effect was more pronounced for IgM. These studies suggest that immunization may have at least one unforeseen benefit, enhancing networks of natural antibodies that may be important in such processes as wound repair and tumor surveillance. Such enhancement of natural antibody function may be particularly important in Western society, where decreased exposure to the environment may be associated with a weakened natural antibody repertoire.