Among individuals with sickle cell disease, acute chest syndrome contributes to 25% of all deaths.
Among people with sickle cell disease—an inherited blood disorder—acute chest syndrome (ACS) is the leading cause of death. The condition is the result of red blood cells becoming stiff, sticky, and sickle shaped and clogging small arteries and veins in the lungs, thus blocking the flow of blood and oxygen in the organ. The airways become inflamed, and patients experience severe chest pain and difficulty breathing. “It’s like having pneumonia,” says Sean Stowell, a transfusion medicine physician-scientist at Brigham and Women’s Hospital in Boston.
Treatment for ACS is typically supportive and involves pain management, respiratory support, and transfusion therapy. In recent decades, researchers have been working toward better understanding the underlying mechanisms that lead to the onset and progression of ACS to develop targeted treatments.
Now, in a new study published July 16 in Science Translational Medicine (DOI: 10.1126/scitranslmed.adl4922), Stowell and colleagues demonstrate how the complement system—a group of proteins that are part of the innate immune system’s defense against pathogens and contribute to initiating an inflammatory response against injuries and infections— drives ACS.
Previous studies have shown that the rapid breakdown of sickled red blood cells results in the release of heme—an iron-containing molecule in hemoglobin—into the bloodstream. That breakdown can activate the complement system. A series of proteins in the system, numbered C1 to C9, get activated sequentially and undergo splitting to form fragments, such C3a and C3b or C5a and C5b. Scientists have suspected that elevated levels of these kinds of fragments may be contributing to severe and painful complications of sickle cell disease.
To understand the complement system’s involvement in ACS, Stowell and his team assessed the blood of 27 sickle-cell-disease patients experiencing ACS for signs of complement activation. The research team found elevated levels of complement fragments, including C3a and C5a, during ACS compared with 4–8 weeks after patients were discharged from the hospital. They also found decreased hemoglobin levels during ACS.
Similarly, in mice with sickle cell disease that received heme injections, the researchers saw increased complement activation, reduced hemoglobin levels, and ACS compared with control animals.
To understand if activating the complement system alone could trigger ACS, the researchers injected sickle-cell-disease mice models with a nontoxic complement-activating protein from cobra venom that’s used to bypass heme. Stowell and his team noted complement activation in both the model and control mice, but only the model group faced a higher risk of developing ACS and dying.
Sickle cells are particularly vulnerable to rupturing when the complement system is activated, Stowell says. The rupturing releases heme, which further activates the complement system and causes more rupturing. “Then everything goes haywire,” Stowell adds.
As a proof of concept, the research team targeted the complement system by blocking the C5 protein to see if that would protect mice with sickle cell disease from ACS. Inhibiting C5 improved lung function and reduced ACS-caused mortality in these rodents.
Stowell thinks targeting proteins upstream of C5 and thus closer to where the complement activation begins may be more effective. “But then you kind of block any ability of complement to be helpful in terms of fighting infections,” he says.
And while Stowell and his colleagues suggest that the complement system may play a more central role in driving ACS than previously postulated, they acknowledge that it’s not the only mechanism involved. Scientists have identified other pathways, but Stowell thinks the complement system potentially plays a more dominant role.
Karina Yazdanbakhsh, the director of research at New York Blood Center Enterprises, who specializes in transfusion medicine and wasn’t involved in the research, says the paper’s findings are extremely exciting. She hopes future studies will compare different complement inhibitors and assess how well these perform against drugs that target other pathways shown to be relevant to ACS.
Stowell and his colleagues are currently conducting research in mice to assess the most effective part of the complement system to target to better protect animals from developing ACS. Such legwork can help inform potential clinical trials in humans.
The COVID-19 pandemic led to an unprecedented acceleration in vaccine development, accompanied by a rapidly expanding body of evidence. Yet, pregnant individuals and children were frequently excluded from early trials, leaving crucial gaps in safety and effectiveness data for these at-risk groups [1]. This scenario highlighted the need for timely, high-quality evidence to guide vaccine development and equitable access [2,3,4,5,6]. Although the acute phase of the pandemic has passed, the lessons it taught remain vital—particularly the importance of generating robust benefit-risk assessments throughout the vaccine lifecycle. Early stages require insight from preclinical and indirect data (e.g., platform technologies or adjuvants). At the same time, subsequent phases must synthesize evolving clinical trial results and real-world evidence to inform policy and public trust [7].
Living systematic reviews (LSRs) offer an effective framework for this process. LSRs support dynamic decision-making across research, regulation, and implementation by continuously updating literature searches and evidence synthesis. They are particularly useful in under-resourced settings where data gaps persist [8]. Our approach consolidates data from high-income and low- to middle-income countries, shedding light on critical gaps in under-resourced settings. By offering a user-friendly evidence map and real-time meta-analyses based on trusted sources, we aim to support decision-making across vaccine development pipelines and implementation strategies worldwide.
To facilitate the rapid synthesis of emerging evidence, we developed an integrated web platform for current and future infectious disease threats. Initially focused on COVID-19 vaccines in pregnancy, our LSR has expanded to include vaccines for chikungunya, Lassa fever, Mpox, and Disease X, particularly for pregnant individuals and children. This initiative is dedicated to continuously gathering and evaluating data on vaccine safety, efficacy/effectiveness, and immunogenicity.
We developed an integrated online platform initially focused on COVID-19 vaccines in pregnancy to address this need. This LSR has since expanded to include vaccines for chikungunya, Lassa fever, Mpox, and Disease X, focusing on pregnancy and childhood populations. This issue contains detailed protocols for two new LSRs, focusing on chikungunya (CRD42024514513, CRD42024516754) [9] and Lassa fever (CRD42024554330, CRD42024556977) [10], which will serve as foundational frameworks for synthesizing emerging evidence. These diseases, prioritized for their public health impact, exemplify the importance of real-time, context-specific evidence to inform future responses.
Chikungunya has recently surged in the Americas, with over 214,000 cases reported in early 2023 [11]. The virus presents a significant burden due to its potential for severe congenital infections and long-term neonatal complications [12]. In August 2023, the first Chikungunya vaccine IXCHIQ™ (VLA1553, Valneva live attenuated vaccine) was approved in the United States [13, 14], marking a pivotal step in addressing this disease. More recently, on February 14, 2025, the U.S. FDA approved VIMKUNYA™ (Bavarian Nordic Chikungunya Vaccine, Recombinant) for individuals aged 12 and older, presenting a major milestone in Chikungunya prevention [15]. This underscores the urgent need for further data on vaccine safety and efficacy, particularly in pregnant women and children, as the risk of chronic morbidity and adverse pregnancy outcomes remains a significant concern. Moreover, climate change is expanding the range of mosquito-borne diseases, increasing the urgency of targeted interventions, including vaccines.
Lassa fever, caused by the Lassa virus and transmitted through contact with rodents, is endemic in West Africa [16] and has been designated as a priority for research and development by the World Health Organization (WHO) [3]. The disease is associated with an estimated 5,000 deaths annually and high mortality rates, particularly in pregnant women (29% maternal mortality in the third trimester) [17, 18] and neonates (87% fetal/neonatal death) [19]. Despite the urgent need for immunization, no approved vaccine is currently available. However, clinical trials are underway, with phase 2 studies in progress to evaluate vaccine candidates [20]. Ensuring the collection of robust safety and efficacy data, especially in children and pregnant women, remains a critical priority.
Evidence synthesis approach
Drawing on our previous experience with a LSR of COVID-19 vaccines administered during pregnancy, we have broadened the project to encompass vaccines for pregnant persons and children against other emerging infectious diseases (https://www.safeinpregnancy.org/) [21, 22]. Our review expanded to include vaccines against pathogens such as chikungunya, Lassa fever, and mpox, which present significant risks in various regions and have the potential for broader transmission. To gather pertinent information, we examine data about vaccine platforms and develop flexible protocols and search strategies that can be swiftly adjusted to address emerging threats. It is important to note that COVID-19 remains a global public health concern and remains in our LSR platform, with immunization coverage during pregnancy still low in several regions [23]. Overcoming barriers to adopting new, effective vaccines poses an even more significant challenge.
Our methodological approach, fully described in the protocols published in this issue [9, 10], based on Cochrane methods for these LSRs and meta-analyses, follows several key steps outlined in our initial article [24]. First, we perform exhaustive searches of published and grey literature across multiple databases—including the Cochrane Library, MEDLINE, EMBASE, LILACS, and Chinese databases—ensuring that studies are captured without language restrictions over relevant periods. Second, after a title and abstract screening accelerated by Nested Knowledge, pairs of authors independently select articles by full text. This web-based software, powered by artificial intelligence, facilitated the dual independent screening by a reviewer and robot screener after training the model with 50 records. Disagreements between humans and the robot were resolved by consensus of the whole review team [25]. They then extract data and assess the risk of bias of included studies, solving disagreements by consensus. We meticulously extract data using REDCap electronic data capture tools, focusing on key aspects such as study identification, participant characteristics, interventions, and outcomes. This approach ensures rigorous data quality control processes and enhances the reliability of our analyses.
Presentation of findings
The data is consolidated and visualized using PowerBI, which provides an interactive dashboard for exploration. It is available at https://www.safeinpregnancy.org/living-systematic-review/. This tool allows stakeholders—including policymakers, researchers, guideline developers, and clinicians—to explore the evidence interactively through filters (e.g., population, vaccine type, outcome) and to generate customized figures, tables, and maps. RShiny enables real-time, user-defined meta-analyses and generates forest plots with pooled estimates and confidence intervals [26]. Users can select the relevant outcomes based on the population of interest and apply filters or subgroups such as vaccine platform, vaccine doses, population, and comparators to show emerging vaccines’ overall safety and efficacy. The certainty of evidence from comparative studies is presented in Summary of Finding tables using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. It evaluates five key domains: risk of bias, inconsistency, indirectness, imprecision, and publication bias. Based on these domains, the certainty of evidence is rated as high, moderate, low, or very low, helping users interpret how much confidence they can place in the effect estimates [24, 27]. This thorough process is supported by meticulous quality control and validation measures to ensure the robustness and reliability of the findings.
A one-way repeated-measures ANOVA revealed a significant main effect of condition on HR, F(4, 156) = 22.74, p < 0.001, partial η² = 0.487. The control condition had the highest mean HR (83.12 ± 6.53 bpm), followed by the tactile condition (77.16 ± 5.28 bpm) and visual condition (74.52 ± 5.76 bpm). The olfactory condition (71.32 ± 4.19 bpm) and tactile-olfactory condition (69.88 ± 4.97 bpm) showed the lowest HR values (Fig. 3), demonstrating the effectiveness of multisensory engagement in reducing physiological stress.
Fig. 3
HR under five sensory stimulation conditions (bpm, beats per minute). Asterisks indicate significant differences based on Bonferroni-adjusted pairwise comparisons: p < 0.05 (*), p < 0.01 (**)
Post hoc pairwise comparisons with Bonferroni correction revealed several significant differences in HR across sensory conditions. HR in the control condition was significantly higher than in the visual (ΔM = 8.60, p < 0.001), tactile (ΔM = 5.96, p = 0.037), olfactory (ΔM = 11.80, p < 0.001), and tactile-olfactory conditions (ΔM = 13.24, p < 0.001). The tactile-olfactory condition showed significantly lower HR compared to control (ΔM = − 13.24, p < 0.001), tactile (ΔM = − 7.28, p < 0.001), and marginally lower HR than the visual condition (ΔM = − 4.64, p = 0.060), though this last difference did not reach statistical significance. No significant difference was found between the tactile-olfactory and olfactory conditions (ΔM = − 1.44, p = 1.000). HR in the olfactory condition was significantly lower than in control (ΔM = − 11.80, p < 0.001) and tactile (ΔM = − 5.84, p = 0.002), but not significantly different from the visual condition (ΔM = − 3.20, p = 0.385). Additionally, no significant difference was observed between the visual and tactile conditions (ΔM = − 2.64, p = 0.869). Among all conditions, the tactile-olfactory stimulus elicited the lowest HR, followed by olfactory and visual stimuli, while the control condition consistently produced the highest HR values. These findings highlight the superior physiological calming effects of combined tactile and olfactory stimulation relative to single-sensory or no-stimulus conditions.
LF/HF
Statistical analysis revealed significant differences in the LF/HF ratio across the five sensory conditions F(4, 156) = 55.09, p < 0.001, partial η² = 0.697. The descriptive statistics showed that the control condition had the highest mean LF/HF ratio (2.62 ± 0.59), while the tactile-olfactory stimuli exhibited the lowest ratio (0.89 ± 0.45) (see Fig. 4), suggesting heightened vagal activity and greater relaxation in the latter condition.
Fig. 4
Mean LF/HF ratio under five sensory stimulation conditions. Asterisks indicate statistically significant differences based on Bonferroni-adjusted pairwise comparisons: p < 0.01 (**)
Further analysis identified significant pairwise differences. The control condition showed significantly elevated LF/HF ratios compared to all other conditions (p < 0.001), including visual (ΔM = 1.205), tactile (ΔM = 1.138), olfactory (ΔM = 1.595), and tactile-olfactory (ΔM = 1.731). The tactile-olfactory condition demonstrated significantly lower LF/HF ratios compared to the visual (ΔM = − 0.526, p = 0.001), tactile (ΔM = − 0.593, p < 0.001), and olfactory conditions (ΔM = − 0.136, p = 1.000); however, the difference with olfactory was not statistically significant. Additionally, tactile stimulation yielded significantly higher LF/HF values than olfactory (ΔM = 0.457, p = 0.005). These results underscore the superior effectiveness of tactile-olfactory stimuli in promoting autonomic balance through enhanced parasympathetic activation and reduced sympathetic dominance.
SDNN
Figure 5 illustrates the distribution of SDNN values for each condition. A one-way ANOVA revealed significant differences in SDNN values across the five sensory conditions F(4, 156) = 20.12, p < 0.001, partial η² = 0.456. The descriptive statistics indicated that the control condition yielded the lowest average SDNN (41.99 ± 6.06), while the tactile-olfactory stimuli demonstrated the highest average SDNN (64.96 ± 10.17). This result suggests that the combination of tactile-olfactory stimuli is most effective in promoting physiological relaxation, as reflected by increased SDNN values.
Fig. 5
Mean SDNN (ms) under five sensory stimulation conditions. Asterisks indicate statistically significant differences based on Bonferroni-adjusted pairwise comparisons: p < 0.01 (**)
Bonferroni-adjusted comparisons revealed that the control condition had significantly lower SDNN values than all other conditions: visual (ΔM = − 13.65, p = 0.002), tactile (ΔM = − 13.66, p < 0.001), olfactory (ΔM = − 21.83, p < 0.001), and tactile-olfactory (ΔM = − 22.96, p < 0.001). Tactile-olfactory stimuli showed significantly higher SDNN values than tactile (ΔM = 9.30, p = 0.012), but did not significantly differ from visual (ΔM = 9.31, p = 0.121) or olfactory (ΔM = 1.13, p = 1.000). The olfactory condition demonstrated significantly higher SDNN than control (ΔM = 21.83, p < 0.001), but did not significantly differ from visual (ΔM = 8.18, p = 0.372) or tactile (ΔM = 8.16, p = 0.118). These findings highlight the potential of multisensory stimulation, particularly tactile-olfactory engagement, in enhancing physiological relaxation as reflected by elevated SDNN.
RMSSD
ANOVA results showed significant variation in RMSSD values across the five sensory conditions F (4, 156) = 59.58, p < 0.001, partial η² = 0.713, indicating that different stimuli conditions influenced participants’ parasympathetic activity as measured by RMSSD. The descriptive analysis shows that the Control condition resulted in the lowest RMSSD values (31.05 ± 4.53), while the olfactory condition had the highest mean value (56.39 ± 9.54) (see Fig. 6). This highlights the significant restorative effect of the olfactory condition on physiological relaxation compared to the other conditions.
Fig. 6
Mean RMSSD (ms) under five sensory stimulation conditions. Asterisks indicate statistically significant differences based on Bonferroni-adjusted pairwise comparisons: p < 0.01 (**)
Bonferroni-adjusted post hoc tests indicated significant differences between the control condition and all other sensory conditions, confirming its significantly lower RMSSD values. Specifically, RMSSD in the control condition was significantly lower than in the visual (ΔM = − 11.50, p < 0.001), tactile (ΔM = − 18.32, p < 0.001), olfactory (ΔM = − 25.34, p < 0.001), and tactile-olfactory conditions (ΔM = − 24.97, p < 0.001). The olfactory condition also showed significantly higher RMSSD values than the visual condition (ΔM = 13.84, p < 0.001). However, no statistically significant differences were observed between the olfactory and tactile conditions (ΔM = 7.03, p = 0.10). These results confirm that multisensory engagement, particularly the olfactory and tactile-olfactory conditions, significantly enhance autonomic flexibility and promote relaxation.
Skin conductance (SC)
Statistical analysis revealed significant differences in SC across the five sensory stimuli conditions F(4, 156) = 49.95, p < 0.001, partial η² = 0.675. Descriptive statistics indicated that the control condition had the highest average SC (3.67 ± 0.85), while the tactile-olfactory stimuli showed the lowest SC values (1.27 ± 0.40) (see Fig. 7), suggesting the greatest reduction in physiological arousal under multisensory stimulation. Pairwise comparisons showed that the control condition significantly differed from all other conditions: visual (ΔM = 1.18, p < 0.001), tactile (ΔM = 1.42, p < 0.001), olfactory (ΔM = 2.06, p < 0.001), and tactile-olfactory (ΔM = 2.40, p < 0.001). Among the experimental conditions, the tactile-olfactory condition demonstrated significantly lower SC compared to visual (ΔM = − 1.22, p < 0.001), tactile (ΔM = − 0.98, p < 0.001), and olfactory (ΔM = − 0.34, p = 0.017). These findings underscore that the tactile-olfactory condition was the most effective in reducing sympathetic arousal, as reflected by significantly lower SC values.
Fig. 7
Mean skin conductance under five sensory stimulation conditions. Asterisks indicate statistically significant differences based on Bonferroni-adjusted pairwise comparisons: p < 0.01 (**)
Anxiety reduction measured by STAI–S scores
Baseline state anxiety levels (STAI-S), assessed prior to any exposure, showed no significant differences across participants assigned to sensory conditions. Notably, anxiety levels significantly increased from baseline to the control condition (36.84 ± 2.54) to the control condition (47.52 ± 6.49), p < 0.001, confirming the stress-inducing nature of the control setting. A repeated-measures ANOVA revealed a significant effect of sensory condition on post-exposure anxiety levels, F(4, 156) = 25.32, p < 0.001, partial η² = 0.513. Descriptive statistics indicated that the control condition elicited the highest anxiety, significantly exceeding all other conditions. In contrast, the tactile-olfactory condition yielded the lowest anxiety (27.40 ± 6.16), suggesting multisensory integration substantially reduced state anxiety (Fig. 8).
Fig. 8
Mean STAI–S scores under five sensory stimulation conditions. Asterisks indicate statistically significant differences based on Bonferroni-adjusted pairwise comparisons: p < 0.05 (*), p < 0.01 (**)
Bonferroni-adjusted post hoc comparisons confirmed that the control condition differed significantly from all other experimental conditions, showing higher anxiety scores than the visual (ΔM = 17.04, p < 0.001), tactile (ΔM = 16.68, p < 0.001), olfactory (ΔM = 18.40, p < 0.001), and tactile-olfactory conditions (ΔM = 20.12, p < 0.001). However, no statistically significant differences were found among the experimental conditions themselves. For example, although tactile-olfactory elicited lower anxiety scores than visual (ΔM = 3.08), this difference was not statistically significant (p = 1.000). Likewise, comparisons between olfactory and tactile conditions yielded non-significant results. These results indicate that each sensory condition significantly reduced anxiety relative to Control. The tactile–olfactory condition produced the largest mean decrease, although differences among experimental conditions were not statistically significant.
Correlations between physiological and psychological measures
The correlation analysis revealed significant relationships between physiological and psychological measures, offering insights into the interplay between autonomic nervous system activity, anxiety, and physiological arousal (Table 2). HR showed a strong positive correlation with the LF/HF ratio (r = 0.532, p < 0.001), suggesting that increased heart rate is associated with heightened sympathetic dominance. In contrast, Mean HR exhibited negative correlations with both SDNN (r = -0.505, p < 0.001) and RMSSD (r = -0.532, p < 0.001), indicating reduced heart rate variability (HRV) with elevated heart rates, reflecting decreased parasympathetic activity and greater stress.
Table 2 Correlation between physiological and psychological responses during and after the 4-min stimulation
The LF/HF ratio correlated positively with SC (r = 0.668, p < 0.001) and STAI–S (r = 0.549, p < 0.001), suggesting that sympathetic dominance is aligned with increased physiological arousal and higher subjective anxiety. Conversely, LF/HF was negatively associated with SDNN (r = -0.464, p < 0.001) and RMSSD (r = -0.671, p < 0.001), further supporting the role of reduced HRV in stress responses.
HRV parameters, SDNN and RMSSD, displayed strong positive intercorrelations (r = 0.527, p < 0.001), with both negatively correlating with SC (SDNN: r = -0.426, p < 0.001; RMSSD: r = -0.615, p < 0.001) and STAI–S (SDNN: r = -0.465, p < 0.001; RMSSD: r = -0.483, p < 0.001). These findings highlight the link between increased HRV and reduced anxiety or physiological arousal. SC positively correlated with STAI–S (r = 0.525, p < 0.001), further indicating the association between heightened physiological arousal and anxiety. These results indicate that under the tactile-olfactory stimuli, physiological and psychological states are closely interconnected.
Investigators created personalized vaccines for 9 patients with high-risk, resectable ccRCC.
Personalized neoantigen vaccines showed early signs of immune activation and durable response in certain patients with clear cell renal cell carcinal (ccRCC), necessitating further research into this therapy, explained David A. Braun, MD, PhD, during a presentation at the 2025 Kidney Cancer Research Summit.
Braun described the rationale and design of a phase 1 trial (NCT02950766) investigating the efficacy of personalized neoantigen vaccines in patients with high-risk, resectable ccRCC; key antitumor strengths of this vaccine; and why the minimal residual disease (MRD) setting may be most optimal for developing therapeutic vaccines for patients with kidney cancer and other diseases with relatively low mutational burdens.
Braun is an assistant professor of medicine (medical oncology) and the Louis Goodman and Alfred Gilman Yale Scholar at the Yale School of Medicine, and a member of the Center of Molecular and Cellular Oncology at Yale Cancer Center in New Haven, Connecticut.
Spotlighting the Promise of Neoantigen Vaccines in RCC
Braun framed his presentation with a glance at the mechanisms of antitumor immunity in kidney cancer. He used the analogy of a car, explaining that the goal of cancer therapy is to drive CD8-positive T cells toward the tumor as quickly and accurately as possible. He noted that historically, this goal has been achieved through immune activation strategies, such as immune checkpoint inhibitors, which he likened to releasing the brakes of the car, as well as novel cytokine and immune agonists, which are comparable to pressing the gas pedals. However, he emphasized that propelling the next generation of kidney cancer therapies will rely on immune navigation approaches, such as antigen-directed therapies, which steer the immune system in the optimal direction.
“Personalized cancer vaccines are an ideal example of how to do that,” Braun stated.
Braun and colleagues saw the potential for neoantigens as effective targets for antitumor immunity and T-cell response based on the previously reported performance of neoantigen-directed treatment approaches across tumor types, including melanoma, pancreatic cancer, and glioblastoma. However, Braun explained that neoantigen-targeting treatment presents a heightened challenge in kidney cancer, which, although immunogenic, has a modest mutation burden and therefore a lower number of targetable neoantigens. Nevertheless, acknowledging the dearth of effective RCC therapies in the adjuvant setting, Braun and colleagues aimed to design a personalized vaccine that could target the neoantigens present in kidney cancer.
Defining the Ideal Patient Population
This small study enrolled 9 patients with high-risk, resectable (stage III or IV) ccRCC who had undergone complete tumor resection.1,2 The investigators created personalized vaccines for these patients through tumor sequencing and neoantigen prediction. These vaccines were composed of synthetic long peptides that contained up to 20 personal neoantigens present in each tumor. These peptides were divided into 4 pools to decrease competition with local lymph nodes in the event of certain epitopes presenting as immunodominant, Braun stated in a question-and-answer session following his presentation.1
Regarding the later-stage patient population, when asked how neoantigen-directed vaccines might perform in earlier-stage tumors, Braun explained, “The immune composition is different in those early-stage tumors, so I don’t think we’ll know until we try. At the same time, some of those earlier-stage tumors tend to have excellent outcomes, so it’s not that [these vaccines] would be for every early-stage tumor, but if we can identify ones that are higher risk, those will be the ones to think about how to target.”
In another answer, he noted that the most convincing levels of success with cancer vaccines have been shown in settings of MRD, such as the adjuvant setting in kidney cancer. Therefore, he expressed that although the vaccines currently in development may not be advanced enough to elicit meaningful responses in the metastatic setting—at least when used alone—he and co-investigators hypothesized that this type of therapy would be most effective in patients with minimal, manageable disease that is nevertheless at high risk of recurrence.
Outlining the Trial Design and Feasibility Analysis
The vaccines were administered with or without ipilimumab (Yervoy) in 2 phases: a priming phase to activate and prime the T cells, followed by a boost phase to facilitate long-lasting T-cell memory.1,2
Regarding the feasibility of manufacturing a neoantigen-directed vaccine for a disease with a low mutational burden, the investigators found that despite the low prevalence of coding mutations in the patient population, they could create a multi-epitope vaccine directed at single nucleotide variants and frameshift insertion deletions that corresponded with kidney cancer driver mutations.
Highlighting the Durable Efficacy of Personalized RCC Vaccines
From there, Braun explained that the second goal of the study was to determine the immunological efficacy of these vaccines.1
“The basic question was: Are the T cells reacting to these neoantigens and capable of recognition?” He asked.
Prior to vaccination, most patients had barely detectable or undetectable levels of neoantigen immunity.1,2 However, after vaccination, neoantigen-specific responses were observed in the peripheral T cells of all treated patients. For instance, at baseline, one patient had no detectable immunity for 3 of the 4 vaccine peptide pools. However, during the vaccination period, this patient exhibited strong peripheral T-cell responses.
When analyzing which neoantigens were associated with responses, Braun reported that, surprisingly, these results were not random. Instead, the investigators saw the most effective immune responses against known kidney cancer driver mutations, such as those in PIK3CA, PBRM1, KDM5C, BAP1, and VHL.
To determine the durability of these responses, the investigators tracked levels of vaccine-specific T-cell clones in the peripheral blood. At baseline, these levels were undetectable or near the lower limit of detection. However, upon vaccination, these levels rose rapidly, persisting through the boost phase. Additionally, Braun spotlighted that in some patients, vaccine-reactive T-cell clones were still observed months to years after vaccination, indicating the durable T-cell immunity elicited by this treatment.
Furthermore, the investigators conducted an in vitro assessment of the antitumor activity of these vaccines by placing vaccine-expanded T cells back on top of the corresponding patients’ tumors. In total, 7 of the 9 patients had generated detectable levels of vaccine-specific T cells that reacted against the autologous whole-tumor cells.
Overall, at a median follow-up of 40.2 months from the time of surgery, none of the enrolled patients had a recurrence of RCC.2 Moreover, no dose-limiting toxicities were reported.
“We’re encouraged by the fact that all 9 patients, despite having high-risk disease, remained free of kidney cancer throughout the study,” he emphasized, noting that 1 patient died of unrelated causes during the study.1,2
Acknowledging How the Study’s Limitations Give Way to Further Research
Braun noted that the small sample size is a key limitation of this research that warrants follow-up studies to determine the clinical relevance of these findings.1
“These neoantigen vaccines are feasible for kidney cancer,” Braun concluded. “They can elicit effective T-cell responses and antitumor activity. At least this preliminary signal of clinical activity sets up [the phase 2] INterpath-004 [trial (NCT06307431)], the next study that will hopefully demonstrate some clinical activity.”
Notably, the phase 2 INterpath-004 trial (NCT06307431) is investigating adjuvant treatment with the mRNA-based personalized cancer vaccine intismeran autogene (V940) plus pembrolizumab (Keytruda) vs placebo plus pembrolizumab in patients with RCC.3
References
Braun DA. Personalized vaccines in kidney cancer: a journey from concept to clinic. Presented at: 2025 Kidney Cancer Research Summit; July 17-18, 2025. Boston, Massachusetts.
Braun DA, Moranzoni G, Chea V, et al. A neoantigen vaccine generates antitumour immunity in renal cell carcinoma. Nature. 2025;639(8054):474-482. doi:10.1038/s41586-024-08507-5
A study of adjuvant intismeran autogene (V940) and pembrolizumab in renal cell carcinoma (V940-004). (INTerpath-004). ClinicalTrials.gov. Updated May 13, 2025. Accessed July 17, 2025. https://clinicaltrials.gov/study/NCT06307431
July 18, 2025 – You know them by names like Ozempic and Wegovy, and for what they can do – help people lose weight. But if you’re among the roughly 1 in 8 Americans who’ve tried GLP-1 drugs – including newer options like Zepbound and Mounjaro, which target more than one hormone – you could be at risk of nutrient deficiency, muscle loss, and even bone loss, unless you make diet and exercise part of the picture.
“Although GLP-1 medications are a major breakthrough in obesity management, lifestyle factors still matter,” said JoAnn E. Manson, MD, a professor of medicine at Harvard Medical School. “Outcomes of patients on these medications are much better with attention to adequate protein intake, healthy diet, good hydration, and regular muscle-strengthening exercises to mitigate the loss of lean body mass.”
Here’s a three-pronged approach to make the most of modern weight loss medications.
1. Maintain Your Muscle
With any weight loss, including that with GLP-1s, you don’t get to pick where you lose it. “Loss of muscle and lean body mass is common on these medications, on average about 25%,” said Manson. Over time, that can lead to bone loss too, especially in older adults or those with sedentary lifestyles.
Eat plenty of protein, the guidelines say. Aim for 1 to 1.5 grams per kilogram (or about half a gram per pound) of body weight each day – or 20 to 30 grams per meal. That’s slightly higher than the standard 15 to 30 grams per meal recommended for all adults.
Exercise is also critical. Start with an evaluation of where you are now, and slowly work up to 150 minutes of cardio (like walking) and two to three 30-minute strength sessions each week, the CDC’s recommended activity level.
Don’t just rely on your doctor to guide you. “Most doctors won’t have the time to thoroughly go through your exercise history, current lifestyle, and any hurdles to beginning exercise,” said Samuel Klein, MD, a professor of medicine and nutritional science at Washington University in St. Louis. “Work with a trainer or someone who is an expert in how to exercise.”
Insurance might cover personal training (if a doctor prescribes it as part of a medically necessary treatment plan), but a better bet: Ask your health care provider if it offers a formal weight management program – many qualify for reimbursement.
2. Sidestep Side Effects
The right eating strategy can help offset potential digestive side effects, such as constipation, nausea, and heartburn. “I recommend smaller, more frequent meals, decreasing fat and salt intake, and chewing slowly so that you reduce the amount of bulk leaving your stomach,” said Klein. That helps your gut better manage the slower-than-usual movement of food into your intestines caused by GLP-1s.
Staying hydrated helps keep things moving, too – and dehydration is a risk of these medications, which suppress thirst along with appetite. The guidelines encourage eight to 12 glasses of water a day, along with soups and water-rich fruits and vegetables like cucumbers and watermelon. Keep dehydrating drinks with things like alcohol and caffeine to a minimum.
3. Keep These Habits – Even Post-Meds
These medications are intended for long-term use, said Jody Dushay, MD, a co-author of the guidelines and assistant professor of medicine at Harvard Medical School. “That said, once people reach a weight loss plateau at the highest tolerated dose, then you move to the weight maintenance phase of treatment.”
That could mean “lowering the dose, staying on the same dose but extending the number of days between injections, or, least commonly, a trial off medication,” Dushay said.
In general, keeping weight off is notoriously difficult, but research suggests that the key to success comes down to one thing: consistency.
“Weight regain is highly individualized and depends on many factors,” said Dushay. Chief among them is an “ongoing engagement in a healthy lifestyle.”
July 18, 2025 – Diarrhea can do much more than ruin your vacation. It sometimes triggers irritable bowel syndrome, a chronic condition that can linger months or even years after you’ve arrived back home.
“It’s important for people to know this can happen,” said gastroenterologist Xiao Jing Wang, MD, an assistant professor at the Mayo Clinic. “We have a lot of patients whose symptoms don’t go away, and they start doing all types of testing. It’s worth it to know that sometimes, these infections can have aftereffects that can linger.”
Nearly 1 in 8 people who get traveler’s diarrhea continue to have symptoms for at least six months, one study found. Of those, nearly 80% have symptoms for at least a year.
IBS causes belly pain and bloating, as well as diarrhea or constipation – or both. The after-travel condition is called post-infectious IBS (PI-IBS), and it can become a lifelong issue for some. “About 25% to 30% continue to have symptoms after 10 years,” said Wang.
What Is Post-Infectious IBS?
Traveler’s diarrhea, which is caused by bacterial, viral, or parasitic infections, essentially falls under the umbrella of food poisoning. You get it from picking up pathogens like campylobacteria and E. coli from poorly sanitized food or water when traveling.
Post-infectious IBS is when your symptoms persist after the infection clears.
“We now believe that a lot of IBS in this country may have started with an enteric [food poisoning] infection,” said Bradley Connor, MD, medical director of the New York Center for Travel and Tropical Medicine in New York City.
There are different theories as to how traveler’s diarrhea triggers IBS, and experts agree it’s likely a combination of things. One theory is that it triggers an autoimmune response due to a mistaken identity of a protein.
The bacteria most commonly linked to traveler’s diarrhea – shigella, campylobacter, salmonella, and E. coli – release a toxin. This toxin resembles a protein in the intestines, called vinculin, that’s important for healthy gut function.
The theory is that the immune system can confuse the two molecules. So it produces antibodies to the toxin – but also to vinculin, said Mark Pimentel, MD, executive director of the Medically Associated Science and Technology program at Cedars-Sinai Medical Center in Los Angeles. Disrupting vinculin can lead to poor gut function and an overgrowth of certain bacteria, which contributes to IBS. Pimentel published a study that found 56% of people with IBS tested positive for vinculin antibodies.
Traveler’s diarrhea can also be caused by parasites, like giardia, which has the highest rate of triggering PI-IBS. But giardia doesn’t release the toxin, meaning something else is probably at play.
It is likely a disrupted gut microbiome, said Wang. Traveler’s diarrhea changes the makeup of good bacteria and bad bacteria in the gut. “We know that there are major distortions in the microbiome when people travel,” said Connor.
The good bacteria have anti-inflammatory properties and help control how well something can pass from the gut to the bloodstream. If the gut gets overwhelmed by bad bacteria, it can lead to chronic inflammation, changes in how the intestines empty, and ultimately the symptoms of IBS.
Risk Factors for Post-Infectious IBS
It’s not known why some people develop PI-IBS, though certain things can increase your risk. It’s more common in women and young people, and some may be more likely to have it because of their genes, said Wang.
The risk tends to be higher if you have a severe case of food poisoning. Also, if you already have PI-IBS, you have a higher chance of getting it again or having more severe symptoms.
What Can You Do to Reduce Your Risk?
The most important thing is to protect yourself from getting traveler’s diarrhea. If you’re visiting high-risk regions, such as developing countries in Central and South America, Mexico, Africa, the Middle East and Asia, take these precautions:
Avoid raw food, including unpasteurized dairy products, and raw or undercooked meat, fish, shellfish, eggs, and produce.
Avoid salads, uncooked vegetables, and raw and unpeeled fruit.
Avoid food and beverages from street vendors.
Avoid tap water and ice unless it’s known to be safe, and use bottled water instead.
Taking bismuth subsalicylate (Pepto-Bismol) preventively has been shown to reduce the risk of getting traveler’s diarrhea. But the recommended dose is two tablets four times a day, which is inconvenient, said Connor.
For people with a higher risk, such as those with PI-IBS or inflammatory bowel disease, doctors may prescribe an antibiotic called rifaximin preventively if they’re travelling to high-risk regions. Rifaximin is poorly absorbed, so it doesn’t negatively affect the gut biome. It’s approved to treat traveler’s diarrhea but used preventively off-label (meaning doctors prescribe it to help prevent diarrhea, even though it’s not FDA approved for that use).
Lastly, if you get food poisoning, avoid taking antibiotics for mild traveler’s diarrhea. Antibiotics can make symptoms worse because they disrupt the microbiome even more. More severe cases caused by certain bacteria may need antibiotics. “It’s OK to use them if your doctor says you need it,” said Wang.
Wastewater surveillance became a popular choice among public health officials looking to track rapid virus mutations and spread patterns during the COVID-19 pandemic. But what if there was a way to detect emerging viruses even faster — or to even sniff out new variants possibly before patients even realize they’re ill?
A new UNLV-led study is moving that dream one step closer to reality by pairing wastewater sample surveillance with artificial intelligence. The results appear in the latest issue of the journal Nature Communications.
Lead author and UNLV neuroscience graduate student Xiaowei Zhuang developed an AI-driven algorithm that scans wastewater to detect budding influenza, RSV, mpox, measles, gonorrhea, Candida auris, or other pathogen variants — often before they’re identified by clinical tests.
Scientists say being able to map virus emergence, mutation, and transmission faster with AI than with existing wastewater surveillance methods could significantly enhance public health officials’ ability to roll out rapid, targeted interventions.
UNLV professor Edwin Oh (Josh Hawkins/UNLV)
“Imagine identifying the next outbreak even before the first patient enters a clinic. This research shows how we can make this possible,” said study co-author Edwin Oh, a professor with UNLV’s Nevada Institute of Personalized Medicine at UNLV. “Through the use of AI we can determine how a pathogen is evolving without even testing a single human being.”
While the study details how the team’s AI method can separate overlapping signals in complex datasets, its real promise lies in on-the-ground impact. “The tool could especially be useful in improving disease surveillance in rural communities, empowering health workers in low-resource settings,” said study co-author and Desert Research Institute research professor Duane Moser.
The research team tested its theory by analyzing nearly 3,700 wastewater samples collected from Southern Nevada wastewater treatment facilities between 2021 and 2023. They discovered that the AI-driven system could accurately identify unique signatures for different virus variants with as few as two to five samples, significantly earlier than current methods.
Previous wastewater detection methods required prior knowledge of a variant’s genetic makeup and relied heavily on clinical data from patients who had already been tested. Though those methods worked well, they were a more reactive approach typically identifying new virus strains after they had already begun widely circulating in a community.
“Wastewater surveillance has enabled more timely and proactive public health responses through monitoring disease emergence and spread at a population level in real time,” says Zhuang. “This new method enhances early outbreak detection to allow for identification of novel threats without prior knowledge or patient testing data, proactively detecting patterns from multiple wastewater samples and making this tool even more effective for public health surveillance moving forward.”
Since 2021, four Las Vegas institutions – UNLV, the Southern Nevada Water Authority (SNWA), the Southern Nevada Health District, and the Desert Research Institute – have collaborated on a public wastewater surveillance dashboard to track emerging cases of COVID-19 and other viruses.
The Nature Communications AI study is one of more than 30 studies these organizations, along with the Cleveland Clinic Lou Ruvo Center for Brain Health, have collaborated on. And the researchers say it is among the first studies to employ an AI approach in enhancing wastewater intelligence.
“Wastewater surveillance has proven to be an effective tool for filling critical data gaps and understanding public health conditions within a community,” said study co-author Daniel Gerrity, principal research microbiologist at SNWA. “The ongoing wastewater surveillance effort is a great example of how collaboration between SNWA, UNLV, and other partners can lead to positive impacts for the local community and beyond.”
About The Study
“Early detection of emerging SARS-CoV-2 Variants from wastewater through genome sequencing and machine learning” was published July 8, 2025 in the journal Nature Communications.
Danville, July 18, 2025 (GLOBE NEWSWIRE) — Blackhawk Plastic Surgery & MedSpa has launched a fresh approach to cosmetic surgical treatments, emphasizing personalized care and the latest medical practices. A highlight of this initiative is the Mommy Makeover at Blackhawk Plastic Surgery in Danville. This makeover combines several cosmetic procedures to help individuals regain their pre-pregnancy body. The goal is to provide personalized experiences and results for individuals seeking aesthetic enhancements.
The Mommy Makeover at Blackhawk Plastic Surgery in Danville includes several body and facial treatments. Options such as breast augmentation, tummy tuck, and liposuction are available. These procedures are designed to address various changes that occur after childbirth. This package offers a comprehensive way to reach one’s aesthetic goals. Dr. Stephen J. Ronan, the founding surgeon, emphasizes the importance of these treatments in boosting self-confidence and overall well-being.
The practice is committed to high standards of care and patient safety. This new offering demonstrates their dedication to meeting each patient’s unique needs through the use of advanced techniques and equipment. With recent advancements in technology and surgical procedures, they provide services that meet modern expectations for cosmetic results.
Dr. Ronan explained, “Our aim is to provide personalized and effective treatments that meet the unique needs of every individual. The Mommy Makeover at Blackhawk Plastic Surgery in Danville combines multiple procedures to offer transformative results.”
For more information about these procedures, please visit the company’s website.
This new service addresses common body changes that occur after pregnancy, with a focus on safety and efficiency. The experts at the facility ensure a thorough consultation process, matching each plan to the patient’s desires and needs. Patients participate in discussions about what to expect and the options available, with professional guidance during their transformation.
Blackhawk Plastic Surgery & MedSpa is recognized for its meticulous care approach, which includes pre-surgery consultations and follow-up visits to monitor progress and ensure optimal outcomes. This comprehensive method underscores their commitment to patient satisfaction and high medical standards.
The staff at Blackhawk Plastic Surgery & MedSpa includes highly trained professionals with many certifications. They adhere to strict safety measures to ensure positive experiences for their patients. This standard of care is vital for building trust and maintaining a strong reputation in the field of cosmetic surgery.
Additionally, the medspa section offers many non-surgical treatments alongside surgical procedures. These services include skin care, laser treatments, and other rejuvenating options, supporting a well-rounded approach to beauty and wellness.
Dr. Ronan added, “We aim to provide a wide range of services so each patient can select what fits their needs and lifestyle best. Our mix of surgical and non-surgical options embodies a holistic approach.”
Blackhawk Plastic Surgery & MedSpa remains committed to integrating patient-centered care with the latest advancements in cosmetic surgery. This ensures every patient receives focused treatment that meets today’s standards and their personal expectations.
For those interested in learning more about the full range of services, including the Mommy Makeover at Blackhawk Plastic Surgery in Danville, exploring options through their website or booking a consultation is encouraged. They combine new medical techniques with patient-focused care innovations, resulting in improved satisfaction and outcomes.
As the desire for personalized cosmetic treatments grows, Blackhawk Plastic Surgery & MedSpa continues to be a leader by offering customized, effective solutions that address the evolving needs of its clients.
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For more information about Blackhawk Plastic Surgery & MedSpa, contact the company here:
Blackhawk Plastic Surgery & MedSpa Dr. Stephan Ronan (925) 736-5757 info@blackhawkplasticsurgery.com Blackhawk Plastic Surgery & MedSpa 3600 Blackhawk Plaza Cir Danville, CA 94506
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An Oregon man contracted plague from his pet cat in January last year—by far the earliest case ever recorded in a calendar year in the state—possibly indicating a seasonal shift of the disease in people.
The man’s case was detailed yesterday in Morbidity and Mortality Weekly Report. Plague, caused by the bacterium Yersinia pestis, is most commonly confirmed in people in late spring or summer. It typically spreads through fleas from rodents.
Oregon had not confirmed a human plague case since 2015, when it recorded two.
Cat contact following knife injury
The man’s saga began on January 19, 2024, when his 2-year-old cat began receiving veterinary care in central Oregon for a neck abscess and vomiting. The cat received oral antibiotics, and a veterinarian drained and excised the abscess on January 24.
The next day, the 73-year-old man cut his right index finger with a kitchen knife and received treatment at an urgent care center. Healthcare practitioners sutured the wound and sent the man home.
Later that day the man had contact with his cat, which was still receiving veterinary care. The next day, on January 26, the man noticed a new tender, raised ulcer on his right wrist. On January 30 he sought care at a local emergency department with symptoms that included skin infection (cellulitis) and swollen lymph nodes extending from the wound on his wrist up to his right armpit.
He was admitted to the hospital and was initially treated with the intravenous (IV) antibiotics ceftriaxone and metronidazole. Hospital lab testing revealed Y pestis in the man’s blood, and plague was confirmed by polymerase chain reaction (PCR) and bacteriophage-lysis testing at the Washington State Public Health Laboratory on February 6.
Veterinarians and medical personnel should maintain a high index of suspicion for Y. pestis infection.
The man’s antibiotic therapy was changed to IV gentamicin and levofloxacin, and his symptoms subsequently improved. He was discharged from the hospital on February 7 and prescribed a 9-day course of oral levofloxacin. “At his follow-up appointment on February 15, he appeared to have made a full recovery, with only mild residual fatigue,” wrote the study authors, who are from the Oregon Health Authority (OHA) and Deschutes County Health Services.
Unfortunately, the man was not able to give the cat its antibiotics after its surgery, and the cat died on January 31. Scientists with the US Centers for Disease Control and Prevention later confirmed Y pestis in tissues from the cat via PCR and tissue culture.
Staying vigilant, even in winter
According to OHA data, previously the earliest case in a calendar year in Oregon occurred in May, way back in 1934. The other 18 cases were confirmed from June through November, in years ranging from 1970 through 2015. Two (10%) of 20 cases in Oregon have proven fatal, 1 of them involving a young child.
The study authors write, “Temperate climates of California’s Central Valley and the Pacific Northwest can be conducive to flea emergence year-round, and various factors, such as unseasonal warm temperatures during the winter, can extend the flea life cycle and potentially promote enzootic [among-animal] transmission.” Fleas can hatch when the temperature is as low as 50°F (10°C), similar to temperatures in central Oregon at the time the cat fell ill.
“The effect of environmental factors, including climate, on plague transmission remains an area of active research,” the authors add.
The effect of environmental factors, including climate, on plague transmission remains an area of active research.
They conclude, “Regular treatment of pets and their surroundings for fleas might reduce the risk for infection with pathogens transmitted by fleas. Y. pestis infection was not considered during the cat’s veterinary screening. Had it been, the pet owner could have been counseled about the risks of animal-to-human plague transmission, potentially preventing zoonotic spread.
“Veterinarians and medical personnel should maintain a high index of suspicion for Y. pestis infection.”
