Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán

Gonzalez-Lara M.F., Román-Montes C.M., Díaz-Lomelí P., Hernández-Ceballos W., Morales-Camilo L., Cervantes-Sánchez A., Cordero-Rangel A., Tejeda-Olán J., Bonifaz-Trujillo A., Ponce-de-León A., Martínez-Gamboa A.

ABSTRACT Correct, rapid, and reliable filamentous fungi identification is crucial for timely diagnosis and therapy. We compared the performance of the FFLv4.0 MALDI Biotyper and MSI-2 to identify filamentous fungi from clinical isolates. We analyzed 307 clinical isolates of Aspergillus spp. , Fusarium spp. , and Mucorales and compared them to sequencing as the reference standard. The overall identification rates to genus ( Mucorales ), section ( Aspergillus ), and species complex ( Fusarium ) level were 96% (296/307) for FFLv4.0 and 78.5% (241/307) for MSI-2. By each genus, correct species identification was achieved by FFLv4.0 and MSI-2 as follows: 72.4% (165/228) and 55.3% (126/228) for Aspergillus species, 17.6% (6/34) and 38.2% (13/34) for Fusarium species, and 88.9% (40/45) and 55.5% (25/45) for the Mucorales . The rates of non-identification by FFLv4.0 and MSI-2, respectively, were 4% (9/228) and 18% (41/228) for Aspergillus spp., 0% and 17.6% (6/34) for Fusarium spp. and 4.4% (2/45) and 42.2% (19/45%) for the Mucorales . Misidentification rates by FFLv4.0 and MSI-2, respectively, were 16.2% (37/228) and 6.1% (14/228) for Aspergillus species, 67.6% (23/34) and 14.7% (5/34) for Fusarium spp., and 0% and 2.2% (1/45) for the Mucorales . The FFLv4.0 MALDI Biotyper outperformed MSI-2 in identifying filamentous fungi from liquid culture spectra.

Omaña D.U., Condori R.C., Torralba A.G., Rojas M.Á., Higuera P.M., Iñiguez A.L.

Velazquez-Meza M.E., Galarde-López M., Cornejo-Juárez P., Bobadilla-del-Valle M., Godoy-Lozano E., Aguilar-Vera E., Carrillo-Quiroz B.A., Ponce de León-Garduño A., Velazquez Acosta C., Alpuche-Aranda C.M.

Metagenomic studies have made it possible to deepen the analysis of the abundance of bacterial populations that carry resistance and virulence determinants in the wastewater environment. In this study, a longitudinal collection of samples of community and hospital wastewater from August 2021 to September 2022 was obtained. Shotgun metagenomic sequencing and bioinformatic analysis were performed to characterize the bacterial abundance, antimicrobial resistance genes (ARGs), plasmids, and virulence factor genes (VFGs) contained in the wastewater. The microbial composition of the community and hospital wastewater showed that the most abundant bacterial phyla detected in all samples were: Proteobacteria, Bacteroides, Firmicutes, Campylobacterota, and Actinobacteria. Seasonal differences in the relative abundances of species, ARGs, plasmids, and VFGs were observed. In this study, a total of 270 ARGs were detected, and it was found that the absolute abundance of ARGs only showed a 39% reduction in the treated wastewater. Furthermore, the ARGs detected in this study were found to encode resistance to antibiotics of the last choice. Our results showed that plasmids carrying resistance genes were more abundant in raw wastewater, and 60% more abundant in hospital wastewater compared to community wastewater. Several of the VFGs detected in this study encode for adhesion, motility, and biofilm formation, which likely allows bacteria to remain and persist in the wastewater environment and survive WWTP treatment systems, thus managing to escape into the environment via treated wastewater.

Tobón-Cornejo S., Sanchez-Tapia M., Guizar-Heredia R., Velázquez Villegas L., Noriega L.G., Furuzawa-Carballeda J., Hernández-Pando R., Vázquez-Manjarrez N., Granados-Portillo O., López-Barradas A., Rebollar-Vega R., Maya O., Miller A.W., Serralde A., Guevara-Cruz M., et. al.

Vitale A., Caggiano V., Leone F., Hinojosa-Azaola A., Martín-Nares E., Guaracha-Basañez G.A., Torres-Ruiz J., Kawakami-Campos P.A., Hissaria P., Callisto A., Beecher M., Dagna L., Campochiaro C., Tomelleri A., Frassi M., et. al.

BackgroundVEXAS syndrome, a recently identified systemic autoinflammatory disorder, poses new diagnostic and management challenges. Based on experience with other autoinflammatory diseases, anti-interleukin (IL)-1, anti-IL-6, anti-tumor necrosis factor (TNF) biotechnological agents, and Janus kinase inhibitors (JAKis) have been widely employed in VEXAS patients. The aim of this study is to evaluate the global effectiveness and safety of biotechnological agents and JAKis using data from the real-world context.MethodsClinical, laboratory, and therapeutic data from VEXAS patients were obtained from the international AIDA Network VEXAS registry.ResultsIn total, 69 VEXAS patients were enrolled in the study. Among them, 12 patients (13 treatment courses) received IL-1 inhibitors, 12 patients (13 treatment courses) were administered anti-IL-6 agents, 8 patients (9 treatment courses) were treated with anti-TNF agents, and 16 patients (17 treatment courses) were treated with JAKis. A complete response was observed in 3 patients (23%) treated with anti-IL-1 agents, 2 patients (15%) receiving IL-6 inhibitors, 1 patient (11%) receiving TNF inhibitors, and 4 patients (23.5%) treated with JAKis. The mean prednisone (or equivalent) dosage significantly decreased during anti-IL-1 treatment (p = 0.01), while glucocorticoids changed during anti-IL-6, anti-TNF, and JAKi treatment in a non-significant fashion. A total of 21 patients experienced adverse events, 3 of which led to death (gut perforation, Legionnaires’ disease, and infectious pneumonia) while on JAKis; treatment withdrawal was required for 8 out of 21 patients.ConclusionIL-1 and IL-6 inhibitors, along with JAKis, represent promising therapeutic options for VEXAS patients, albeit careful monitoring is mandatory to control disease activity and ensure safety.

Gandhi R.T., Landovitz R.J., Sax P.E., Smith D.M., Springer S.A., Günthard H.F., Thompson M.A., Bedimo R.J., Benson C.A., Buchbinder S.P., Crabtree-Ramirez B.E., del Rio C., Eaton E.F., Eron J.J., Hoy J.F., et. al.

ImportanceNew data and new antiretroviral drugs and formulations continue to become available for the prevention and management of HIV infection.ObjectiveTo provide updated recommendations for HIV treatment and clinical management and HIV prevention.MethodsA panel of volunteer expert physician scientists were appointed to provide updated consensus recommendations for 2024. Relevant evidence in the literature since the last report was identified from PubMed and Embase searches (which initially yielded 3998 unique citations, of which 249 were considered relevant); from ongoing monitoring of the literature by the panel members; from data submitted by product manufacturers; and from studies presented at peer-reviewed scientific conferences between June 2022 and October 2024.FindingsAntiretroviral therapy continues to be recommended for all individuals with HIV. For most people with HIV, initial regimens composed of an integrase strand transfer inhibitor (InSTI), specifically bictegravir or dolutegravir, with 2 (and in some cases 1) nucleoside or nucleotide reverse transcriptase inhibitors are recommended. Recommendations are made for those with particular clinical circumstances, such as pregnancy and active opportunistic diseases, as well as for those unable to take InSTIs. Regimens may need to be changed for virologic failure, adverse effects, convenience, or cost, among other reasons. Long-acting injectable therapy is available for those who prefer not to take daily oral medications and for people struggling with adherence to daily therapy. Recommendations are provided for laboratory monitoring, management of substance use disorders and weight changes, as well as use of statins for cardiovascular disease prevention. For HIV prevention, oral (daily or intermittent) and injectable long-acting medications are effective options for people at increased likelihood of HIV exposure. Further, new tools for maintaining health and well-being among people with HIV, such as doxycycline postexposure prophylaxis to avert sexually transmitted infection, and strategies to treat substance use disorders, are recommended. Disparities in HIV acquisition and care access are discussed and solutions proposed.ConclusionsNew approaches for treating and preventing HIV offer additional tools to help end the HIV epidemic, but achieving this goal depends on addressing disparities and inequities in access to care.

Ayala-Moreno M.D., Martínez-Serrano P.A., Melgarejo-Gutiérrez M.A., Hernández-Mondragón A.R., Martínez-Basila A., Martínez-Coronado A., Losana-Valencia M.J., Vargas-Medina E., Colín-Ramírez E., Benítez-Rico A.

Home confinement due to Coronavirus Disease 2019 (COVID-19) led to lifestyle changes that increased sleep disturbances, particularly in areas with higher infection and mortality rates. This study is a retrospective study based on data collected through an online survey conducted during the COVID-19 confinement. It aims to analyze changes in sleep quantity and quality and their association with lifestyle changes in the metropolitan area of Mexico City. A total of 899 adults from this area completed an online questionnaire between June 2020 and February 2021. This study assessed sleep quantity, sleep quality, insomnia symptoms, and lifestyle changes during the confinement period. Results showed that sleep quantity increased (7.10 ± 1.37 vs. 7.43 ± 1.42 h, p < 0.0001), with more participants, especially young adults and women, reporting later bed and wake-up times. The Pittsburgh Sleep Quality Index increased by 1.4 units, with poor sleep quality associated with lifestyle during confinement. Insomnia symptoms, sleep latency, and poor sleep quality also increased, particularly in women. Males and those without chronic comorbidities were less likely to experience poor sleep quality, while tobacco use and later bedtimes increased this risk. This study concludes that, while sleep quantity increased, sleep quality declined, particularly among young adults, women, and those with unhealthy lifestyles. These findings could guide sleep health initiatives tailored to specific lifestyle changes in different population groups.

Zambrano E., Ibáñez C.A.

Abstract In 2024, we are celebrating the 280th anniversary of Jean-Baptiste Lamarck, whose early theories on inheritance and environmental adaptation have advanced the foundational concepts of Developmental Origins of Health and Disease (DOHaD). This proposal aims to explore how some Lamarckian ideas align with contemporary understandings of how environmental factors in early life can affect health throughout an individual’s lifetime and across generations. This text not only honors an important historical milestone but also reflects on how a DOHaD notion might have been present since the earliest years of biological science. It bridges historical scientific thought with present-day scientific research.

Caggiano V., Vitale A., Hinojosa-Azaola A., Guaracha-Basañez G.A., Ruscitti P., Cipriani P., Tharwat S., Elberashi H.M., Othman E.E., Conforti A., Gimignani G., Erten S., Barone P., Thabet M., Sota J., et. al.

During the last decade, spondyloarthritis (SpA) has increasingly been considered a disease at the crossroads between autoimmunity and autoinflammation. Some patients may even present with autoinflammatory-related manifestations, including fever, hidradenitis suppurativa, other neutrophilic dermatoses, and an unusually high increase in inflammatory markers. Therefore, a subgroup of SpA patients may be identified, and specific details about this cluster need to be investigated. In this regard, the AutoInflammatory Disease Alliance (AIDA) Network has developed a registry primarily aimed at better understanding the autoinflammatory aspects of SpA. The development of this Registry favors the systematic assessment of SpA through the lens of autoinflammation, giving a voice to patients with atypical presentations, and favoring a personalized treatment approach. By supporting research and facilitating the transfer of new evidence to clinical practice, this specific registry has the potential to significantly advance the field of rheumatology and enhance the lives of patients suffering from this complex and multifaceted disease.

Buchanan L., Calkins M., Kalayjian T., Norwitz N.G., Teicholz N., Unwin D., Soto-Mota A.

BackgroundCost, scalability, and durability represent major challenges to the implementation of intensive lifestyle treatments for obesity and diabetes. We previously reported pilot data from a 6-month intervention in which a self-insured manufacturing company partnered with a metabolic health clinic that utilizes therapeutic carbohydrate reduction (TCR), asynchronous monitoring, and a community-based approach to treat employees with metabolic disease. This manuscript presents weight loss and cost-savings from deprescription at the 12-month time point.Methods50 employees, mean BMI 43.2 ± 8.7 kg/m2, 64% with prediabetes or type 2 diabetes, were enrolled in the multimodal TOWARD telemedicine intervention, which includes: Text-based communications, Online interactions, Wellness coaching, Asynchronous education, Real-time biofeedback and remote monitoring, and Dietary modifications that emphasizes TCR.Results41 completed the one-year intervention. Mean weight loss for the 50 subjects in the intention-to-treat analysis was 19.5 ± 11.4 kg, corresponding to 15.5% total body weight loss with concomitant deprescription of 96 medications, while starting only 8 medications. In patients who discontinued GLP-1 receptor agonists, weight loss continued or was maintained. Annualized cost savings from the TOWARD approach were approximately -$1700 per patient, as compared to an annualized cost burden of roughly +$13000 per patient for a GLP-1 receptor agonist.ConclusionThe TOWARD approach represents a scalable metabolic health intervention that demonstrates robust improvements in weight while simultaneously allowing for deprescription leading to substantial cost savings. TOWARD could serve as a scalable tool to facilitate intensive lifestyle intervention with efficacy on par with GLP-1 receptor agonists.

Hernández‐Flores L.A., López‐Martínez J.B., Rosales‐de‐la‐Rosa J.J., Aillaud‐De‐Uriarte D., Contreras‐Garduño S., Cortés‐González R.

ABSTRACTIntroductionSince its introduction in 2022, public‐access conversational AI, exemplified by ChatGPT and Gemini, has been increasingly utilized in medical decision‐making, though its impact is questionable. This study aims to evaluate its efficacy in assessing complex oncologic cases compared to a multidisciplinary tumor board (MTB) comprising experts from various specialties.MethodsA 2‐year retrospective analysis was conducted on 98 oncological cases at a reference medical center in Mexico City. A MTB comprising surgical oncologists, medical oncologists, radio‐oncologists, pathologists, among others, reviewed and discussed each case to determine management strategies. We evaluated four key decision points, dichotomized as either affirmative or negative: the need for new imaging studies, radiation therapy, chemotherapy, and surgery. Comprehensive medical documentation accompanied each case. We then compared AI's decisions with those of the MTB using the same criteria and conducted a Cohen's Kappa test to assess agreement.ResultsAgreement between ChatGPT (4o) and Gemini (1.5 Flash), and the MTB ranged from none to slight for additional imaging studies (Gemini: κ = 0.100, p = 0.087; ChatGPT 4o: κ = 0.024, p = 0.592) and chemotherapy (Gemini: κ = 0.089, p = 0.316; ChatGPT 4o: κ = 0.336, p = 0.001). Moderate agreement was observed for decisions regarding surgery (Gemini: κ = 0.194, p = 0.046; ChatGPT 4o: κ = 0.467, p = < 0.001) and radiotherapy (Gemini: κ = 0.214, p = 0.012; ChatGPT 4o: κ = 0.525, p = < 0.001).ConclusionsBoth ChatGPT and Gemini showed moderate agreement with the multidisciplinary tumor board on decisions regarding surgery and radiotherapy. ChatGPT also showed moderate agreement in chemotherapy, but further assessment is needed for other interventions. ChatGPT proved to be superior to Gemini in most key points. The potential of these public access AI in oncology warrants continued exploration to refine its utility in clinical practice.

López-Ruíz M., Barrios-Payán J., Maya-Hoyos M., Hernández-Pando R., Ocampo M., Soto C.Y., Mata-Espinosa D.

Background/Objective: Finding new targets to attenuate Mycobacterium tuberculosis (Mtb) is key in the development of new TB vaccines. In this context, plasma membrane P-type ATPases are relevant for mycobacterial homeostasis and virulence. In this work, we investigate the role of the copper-transporting P-type ATPase CtpA in Mtb virulence. Methods: The impact of CtpA deletion on Mtb’s capacity to overcome redox stress and proliferate in mouse alveolar macrophages (MH-S) was evaluated, as well as its effect on Mtb immunogenicity. Moreover, the influence of CtpA on the pathogenicity of Mtb in a mouse (BALB/c) model of progressive TB was examined. Results: We found that MH-S cells infected with wild-type (MtbH37Rv) or the mutant strain (MtbH37RvΔctpA) showed no difference in Mtb bacterial load. However, the same macrophages under copper activation (50 µM CuSO4) showed impaired replication of the mutant strain. Furthermore, the mutant MtbΔctpA strain showed an inability to control reactive oxygen species (ROS) induced by PMA addition during MH-S infection. These results, together with the high expression of the Nox2 mRNA observed in MH-S cells infected with the Mtb∆ctpA strain at 3 and 6 days post-infection, suggest a potential role for CtpA in overcoming redox stress under infection conditions. In addition, MtbΔctpA-infected BALB/c mice survived longer with significantly lower lung bacterial loads and tissue damage in their lungs than MtbH37Rv-infected mice. Conclusions: This suggests that CtpA is involved in Mtb virulence and that it may be a target for attenuation.

Rioja P., Passarella C., Angel M., Valderrama W., Bosma F., Anguera G., Gomez V., Ruiz-Granados Á., Plata D., Zapata Laguado M.I., Orta-Ruiz A., Gandur-Quiroga M.N., Bourlon M.T., Grande E., Manneh R., et. al.

502 Background: Deferred cytoreductive nephrectomy (dCN) is an emerging, strategy in the management of metastatic renal cell carcinoma (mRCC), applied selectively to patients who demonstrate a favorable response to initial systemic therapy. This study aimed to assess the clinical impact of dCN within the context of sequential treatment management. Methods: A multi-institutional retrospective evaluation. The descriptive analysis was performed to examine the demographic and clinical characteristics. Progression-free survival (PFS) and overall survival (OS) were analyzed by the Kaplan-Meier method. A level of p < 0.05 was considered significant. Results: With a median follow-up of 19 months (1-174 months), 50 patients were divided into three groups: 46% received IO+TKI, 24% received IO+IO, and 30% received TKI. Of the cohort, 66% were male, with median age of 60.6 years. All had clear cell histology, and 76% were intermediate IMDC risk. The most common metastatic sites were lungs (50%), lymph nodes (36%), and bone (32%). The median time from systemic therapy to cytoreductive nephrectomy (CN) was 6 months. Notably, 26% did not restart treatment post-CN, and 6% discontinued pre-CN (two due to toxicity, one due to progression). Median PFS was 36 months, with a 5-year PFS rate of 40%. Analysis by IMDC risk and type of treatment showed no significant differences. However, patients with a Karnofsky score (KS) ≤80% had a lower risk of progression than those with KS >80% [HR: 0.31, 95% CI (0.13-0.75), p=0.01] and those achieving complete response had a significantly lower risk of progression [HR: 8.59, 95% CI (1.1-67), p=0.042]. Median OS was 91 months, with no significant differences between groups. Conclusions: This study demonstrates that dCN can offer a therapeutic advantage especially in selected patients who achieve favorable responses to upfront systemic therapy. Careful patient selection is crucial to maximize the potential benefits of delayed surgery, reduce perioperative risks and improve oncological outcomes. Larger patient cohorts and well-designed prospective clinical trials are essential to solidify these findings and establish evidence-based guidelines.

Motzer R.J., Escudier B., Burotto M., Powles T., Apolo A.B., Bourlon M.T., Shah A.Y., Porta C., Suárez C., Barrios C.H., Richardet M.E., Gurney H., Kessler E.R., Tomita Y., Bedke J., et. al.

439 Background: N+C showed significant benefits vs S in progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) for patients (pts) with previously untreated aRCC from the phase 3 CheckMate 9ER trial ( N Engl J Med 2021; 384:829–41). We report final results for the trial with a long-term follow-up (min, >5 y), including updated efficacy in intent-to-treat (ITT) pts and by International Metastatic RCC Database Consortium (IMDC) risk, and safety. Methods: Pts with aRCC were randomized to receive first-line N 240 mg every 2 wk + C 40 mg QD or S 50 mg QD (4 wk of each 6-wk cycle) until disease progression or unacceptable toxicity (2 y N max.). The primary endpoint was PFS per RECIST v1.1 by blinded independent central review (BICR). Secondary endpoints included OS, ORR per RECIST v1.1 by BICR, and safety. Results: Median follow-up was 67.6 (range, 60.2–80.2) mo. In ITT pts (N+C, n = 323; S, n = 328), PFS favored N+C vs S (hazard ratio [HR], 0.58 [95% CI, 0.49–0.70]). Median (95% CI) PFS (mPFS) was 16.4 (12.5–19.3) vs 8.3 (7.0–9.7) mo, respectively; 60-mo PFS rates were 13.6% vs 3.6%. OS also favored N+C vs S (HR, 0.79 [95% CI, 0.65–0.96]). Median (95% CI) OS (mOS) was 46.5 (40.6–53.8) vs 35.5 (29.2–42.8) mo, respectively; 60-mo OS rates were 40.9% vs 35.4%. ORR was greater with N+C vs S (55.7% vs 27.4%; complete response [CR], 13.9% vs 4.6%). Duration of response (DOR) rates at 60 mo with N+C vs S were 22.0% vs 10.0%, respectively. Efficacy by IMDC risk groups is reported in the Table. In all treated pts (n = 320 each arm), any-grade (grade ≥ 3) treatment-related adverse events occurred in 97.5% (67.8%) vs 93.1% (55.3%) with N+C vs S. No new deaths due to study drug toxicity occurred since the last database lock. Additional subgroup analyses will be presented. Conclusions: Long-term efficacy benefit was observed with N+C over S in this final follow-up from CheckMate 9ER. There were no new safety signals. The results continue to support N+C as a standard of care for previously untreated aRCC. Clinical trial information: NCT03141177 . FAVN+C; n = 74 FAVS; n = 72 INTN+C; n = 188 INTS; n = 188 PoorN+C; n = 61 PoorS; n = 68 PFS HR (95% CI) 0.67 (0.46–0.97) - 0.63 (0.50–0.80) - 0.36 (0.23–0.56) - mPFS (95% CI), mo 21.4 (12.8–24.6) 12.8 (9.4–16.6) 16.6 (11.3–21.7) 8.5 (6.9–10.4) 9.9 (5.9–17.7) 4.2 (2.9–5.7) 60-mo PFS rate, % 15.1 3.9 12.7 4.7 15.7 0 OS HR (95% CI) 1.08 (0.70–1.66) - 0.86 (0.67–1.11) - 0.49 (0.33–0.74) - mOS (95% CI), mo 53.7 (40.8–70.7) 58.9 (46.1–NE) 47.4 (38.2–55.8) 36.2 (25.7–46.3) 34.8 (21.4–53.4) 10.5 (6.8–20.7) 60-mo OS rate, % 46.3 49.4 41.2 38.2 33.1 12.9 ORR (95% CI), % 66.2 (54.3–76.8) 43.1 (31.4–55.3) 55.9 (48.4–63.1) 27.7 (21.4–34.6) 42.6 (30.0–55.9) 10.3 (4.2–20.1) CR, % 16.2 6.9 15.4 4.8 6.6 1.5 60-mo DOR rate, % a 22.0 NE 19.0 13.0 37.0 0 FAV, IMDC favorable; INT, IMDC intermediate; NE, not estimable; poor, IMDC poor. a Based on pts with objective response.

Zegarra-López M., Aranda-Gutierrez A., Muñoz Lozano J.F., Villarreal-Garza C.

PURPOSE Limited information exists about medical oncology fellowship programs in Latin America. Our study aimed to clarify unknowns, with the goal of identifying areas for improvement and potential expansion of fellowships. MATERIALS AND METHODS Sixteen medical oncologists, each from a different Latin American country, were surveyed using an online questionnaire. Descriptive statistics were used to summarize the collected variables. RESULTS In total, 232 fellowship programs exist in the surveyed nations, of which 444 medical oncologists graduate every year. Only Argentina, Brazil, Chile, Mexico, and Peru have more than five active fellowship programs. Honduras and Nicaragua did not report any fellowship programs. These nations—along with Colombia, Ecuador, El Salvador, Guatemala, and Peru—depend on foreign education for the training of their medical oncologists. Only one of every 50 medical graduates pursues a career path in medical oncology, and a mere 2.2% of internal medicine residents transition into the field. Nearly half of the data were collected through word of mouth, as many countries lack official, publicly accessible sources for some of the variables studied. CONCLUSION This study serves as a pioneering effort that future research groups can build upon. We believe that addressing the shortage of medical oncologists in Latin America by increasing the number of locally trained fellows is the most effective way to swiftly and sustainably improve cancer outcomes.