Internal medicine (IM) education in resource-limited hospitals is constrained by heavy workloads and imaging limited to plain radiography. Point-of-care ultrasound (POCUS) supports experiential learning and diagnostic reasoning, yet no rounds-integrated IM curricula have been described in Latin America, and most programs stop short of practice-based bedside assessment. To implement and evaluate a rounds-integrated POCUS curriculum in a resource-limited IM setting. Hospital Nacional de Coatepeque (228-bed Guatemalan public hospital). Eight final-year medical students without formal ultrasound training. The curriculum combined flipped-classroom prework, a 2-day course focused on pleural and abdominal fluid detection, and a 2-month longitudinal program embedding POCUS into daily rounds, with Butterfly Cloud portfolio review, WhatsApp-based feedback, and designation of three learners as local “champions” in a train-the-trainer model. Knowledge and confidence gains largely persisted at 2 months. Hands-on performance was strongest for pelvic/bladder view acquisition, artifact recognition, and image optimization, and lowest for spine sign recognition and probe orientation and manipulation. Barriers included probe scarcity and limited institutional support; champions emerged as key drivers of peer learning. Rounds-integrated POCUS training is feasible in resource-limited settings and may support early skill development when paired with longitudinal mentorship and local champion development.

In 2024, Guatemala declared a national public health emergency for dengue virus (DENV) in response to a 5-fold increase in cases. As most infections are asymptomatic, it is difficult to estimate the true underlying seroprevalence of infection. Knowing individual- and population-level serostatus is critical for vaccine intervention efforts, as only those who are seropositive should receive the vaccine. Understanding characteristics of the seropositive population will help target disease-prevention interventions. Overall Seroprevalence of Primary DENV Infection by Year We analyzed serum blood samples from the AGRI cohort, a longitudinal study of agricultural workers in southwest Guatemala, using an IgG-based multiplex bead assay conjugated to DENV1-4/ZIKV EDIII. A decision-tree algorithm classified infection as primary DENV if the mean fluorescence intensity (MFI) for a DENV serotype accounted for >33% of total MFI for all flaviviruses. We calculated annual population-level seroprevalence of primary DENV infection, adjusting for test sensitivity and specificity, and examined associations between seropositivity and demographic, occupational, and socioeconomic factors. Among 696 participants with at least one sample, primary DENV seroprevalence increased from 51% in 2020 to 63% in 2021 and 76% in 2022. There was a significant difference in primary DENV seropositivity among field foremen (92% seropositive, 8% seronegative, p< 0.01) vs other farm job types (approximately 70% seropositivity). No other significant associations were found. We currently have an additional ∼7,000 samples collected through 2024 in laboratory analysis and will be incorporating geospatial data for spatial analysis. While specific risk factors remain unclear, our findings highlight increasing DENV seroprevalence in the population, underscoring the need for ongoing surveillance and targeted interventions. Blair Weikel, MPH, Merck: Grant/Research Support Molly Lamb, PhD, Merck: Grant/Research Support Daniel Olson, MD, Fundacion para la Salud Integral de los Guatemaltecos: Board Member|Merck: Grant/Research Support|Roche Diagnostics: Grant/Research Support

The NCCN Guidelines for Melanoma: Cutaneous provide strategies for the diagnosis, treatment, and follow-up of patients with cutaneous melanoma, which is among the most common cancers in the United States. The outcome of cutaneous melanoma is significantly influenced by stage at initial presentation. Generally, localized disease and smaller primary tumors have been associated with more favorable prognosis. Thus, the select content featured in this issue focuses on risk factors associated with cutaneous melanoma development and which should be considered during an initial assessment. These include (1) phenotypic predispositions, (2) personal medical history or comorbidities, (3) genetic predispositions, and (4) environmental factors.

2616 Background: High-dose IL-2 demonstrates modest activity in melanoma and RCC but its use is limited by severe toxicity. AB248 is a novel IL-2 fusion protein of an attenuated IL-2 mutein linked to an antibody targeting CD8β that features >500-fold selectivity for CD8+ T cells and shows strong anti-tumor activity both alone and with anti-PD1 in preclinical models. In addition to CD8+ T cell expansion and activation, the drug avoids NK cell toxicity and Treg-mediated immunosuppression. Methods: NCT05653882 is a phase 1A/B study investigating the safety, pharmacokinetics (PK), pharmacodynamics (PD) and anti-tumor activity of AB248 alone or with pembrolizumab in locally advanced/metastatic solid tumor malignancies, including melanoma, having previously progressed through PD-1/PD-L1 checkpoint blockade. The study’s primary objective was to assess the safety and tolerability of AB248 alone and in combination with pembrolizumab. Results: As of December 1, 2025, 61 patients (pts.) were treated with monotherapy (MT) at 6 dose levels across 3 schedules (Q2W at 0.02mg/kg-0.75mg/kg; QW at 0.15mg/kg; Q3W at 0.3mg/kg). 68 additional pts. were treated with combo therapy (CT) at Q3W 0.15-0.3mg/kg and step-up dosing. The most common TEAEs (> 95% G1-2) among all pts. were fatigue (50%), rash (49%), nausea (43%), chills (33%), pyrexia (32%), vomiting (32%) and diarrhea (30%). Maximum tolerated doses (MTDs) were 0.5 mg/kg for MT Q2W and 0.15 mg/kg for CT Q3W. An MTD was not reached for CT step-up dosing. 41 cutaneous (cut) and mucosal (muc ) melanoma pts. were evaluable for response across MT and CT dose cohorts, with 95% of pts. having received prior IO doublet therapy (anti-PD1 + anti-CTLA or anti-LAG3) and 83% having received ≥ 2 anti-PD1 regimens. Among evaluable cut melanoma pts., 2 confirmed PRs (18%) were observed among 11 pts. enrolled at higher MT dose levels (net tumor reductions of 78.8% and 87.2%) and 2 confirmed PRs (12%) were observed among 16 CT pts. (37.5% and 57.5%). Among 11 muc melanoma pts., 3 confirmed PRs (27%) were observed in CT dosing. One additional muc melanoma pt. received 0.5 mg/kg MT and remained on study with SD > 15 mos. AB248 exhibited dose-proportional PK that is comparable between MT and CT dosing. Peripheral PD data demonstrated robust and preferential CD8+ T cell expansion, with >20X expansion in MT (0.3 mg/kg and above) and >11X expansion in CT dosing (0.15 mg/kg and above). Further data on safety, PK, PD, and preliminary anti-tumor activity will be presented. Conclusions: AB248 demonstrates robust anti-tumor activity across heavily IO-pretreated patients with metastatic melanoma (incl. mucosal melanoma). Combined with an acceptable safety profile, favorable PK and differentiated PD, the drug’s anti-cancer activity merits further investigation. Clinical trial information: NCT05653882 .

2536 Background: CHM-2101 is a Cadherin 17 directed autologous CAR T-cell product being developed to address the continuing unmet medical need for effective therapy against relapsed or refractory gastrointestinal (GI) cancers. Solid tumors of the GI tract such as gastric cancer, colorectal cancer (CRC) and neuroendocrine tumors (NETs) are devastating diseases associated with poor outcomes and more than 1.3 million global deaths annually. Despite advances in surgical and medical treatment of these solid tumors, the prognosis for patients with relapsed or refractory disease remains poor. There remains a need for innovative and effective treatments for patients with advanced and treatment-recalcitrant GI malignancies. Methods: The ongoing clinical trial is a seamless Phase 1/2 study enrolling subjects with gastric cancer, CRC or NETs of the midgut or hindgut. Enrolled subjects undergo screening and apheresis to enable manufacturing of CHM-2101. After completing apheresis, bridging therapy is permitted to provide disease control. After confirming successful CHM-2101 manufacturing and washout of bridging therapy, study subjects receive 3 days of lymphodepleting chemotherapy (fludarabine 30mg/m2/day and cyclophosphamide 500mg/m2/day). After two days of rest, subjects receive a one-time IV infusion of CHM-2101. Results: As of October 24, 2025, 13 subjects have been enrolled with 2 screen failures. Eleven of eleven successful manufacturing runs enabled treatment of 9 subjects to date (4 subjects at Dose Level 1 and 5 subjects at Dose Level 2). Most AEs were Grade 1-2. Aside from lymphodepleting chemotherapy-related cytopenias, Grade 3 Treatment-Related Adverse Events (TRAEs) were Cytokine Release Syndrome (CRS) and Enterocolitis in 1 subject each. There have been no Grade 4 or 5 TRAEs or DLTs. After IV infusion, CHM-2101 was noted to expand and persist (by flow and ddPCR) in the peripheral blood of all treated subjects. Conclusions: CHM-2101 has demonstrated cellular expansion and persistence with clinical tolerability in study subjects with advanced GI cancers at two dose levels. Enrollment of patients at Dose Level 3 is ongoing at US Cancer Centers. Clinical trial information: NCT06055439 .

Background Influenza virus surface protein hemagglutinin (HA) is the primary target of antibodies that protect against influenza virus infection and disease. The viral composition of the annual influenza vaccines may differ for northern (NH) and southern (SH) hemisphere seasons. Vaccine formulation for Guatemala has fluctuated between NH and SH; some years both are used.Phylogenetic tree of influenza A H3N2 HA sequences collected in southwest Guatemala from in the 2021/2022 and 2024 seasonsInfluenza A H3 sequences were aligned along northern and southern hemisphere reference vaccine strains for the respective season. Southern hemisphere reference strain (A/Thailand/8/2022) showed the closest relationship to circulating strains.Phylogenetic tree of influenza B HA sequences collected in southwest Guatemala from in the 2021/2022 and 2024 seasonsBoth reference strains matched the circulating strains' clade for the respective season. Methods We used the MinION (Oxford Nanopore Technologies) to sequence influenza A(H3N2) (n=60) and influenza B (n=9) virus samples collected in southwest Guatemala from December 2021–January 2022 and January–June 2024. HA protein sequence alignment with vaccine strains was conducted. Maximum likelihood trees were generated to estimate evolutionary distance between circulating and vaccine strains and were compared using Wilcoxon sign rank test. Mutation characterization was performed using FluSurver. Results For 2021/2022 A(H3N2) samples, we found a mean evolutionary distance of 9.7 amino acid (AA) substitutions/100 sites compared to the SH vaccine strain and 5.9 to NH (SH to NH distance comparison p < 0.0001). None of the vaccine strains (3C.2a1b.1b/3C.2a1b.2a.1a) shared clades with circulating viruses (3C.2a1b.2a.2a.3). For the 2024 A(H3N2) samples, analysis revealed a mean distance of 2.3 compared to SH and 5.2 to NH vaccine strains (SH to NH distance comparison p < 0.001). Sequences from this period had a shared clade (3C.2a1b.2a.2a.3a.1) with the SH vaccine strain. Mutation characterization identified one of the 2024 samples with a mutation that removes a potential glycosylation site (T151A). Influenza B virus sequences belonged to the same clade as the vaccine viruses (V1A.3 for 2021/2022 and V1A.3a.2 for 2024). Conclusion The 2021/2022 circulating sequences in the region showed more AA similarity with the NH A(H3N2) compared with the SH vaccine virus sequence. In contrast, the 2024 circulating A(H3N2) strains showed more AA similarity and shared the same clade with the SH vaccine virus sequence. Our data may inform a proposed Guatemala-wide analysis to evaluate if location-specific NH/SH formulation recommendations could result in a better match between vaccine viruses and circulating strains. Molly Lamb, PhD, Merck: Grant/Research Support Daniel Olson, MD, Fundacion para la Salud Integral de los Guatemaltecos: Board Member|Merck: Grant/Research Support|Roche Diagnostics: Grant/Research Support

Essential agricultural workers in Central America and their households faced a high force of infection during the COVID-19 pandemic. Here, we evaluated if pre-existing seropositivity and vaccination (hybrid immunity) influenced SARS-CoV-2 infection risk and duration of shedding in an agricultural community in rural Guatemala. Individuals from 70 households were enrolled in a community cohort. From September 2021 to December 2022, all participants reported symptoms twice-weekly and provided saliva weekly for SARS-CoV-2 RNA testing by reverse transcriptase polymerase chain reaction (RT-PCR). Following detection of SARS-CoV-2 in a household, all enrolled household members provided saliva tested three times weekly for four weeks for RT-PCR testing to determine the duration of viral shedding among infected participants. We selected 119 SARS-CoV-2 PCR-positive individuals and 101 month-matched controls to measure nucleocapsid IgG and Omicron neutralizing antibody (NAb) titers. Compared to uninfected controls, SARS-CoV-2 cases were more frequently female (60.5

Abstract Introduction: Nectin-4 has emerged as a clinically validated antigen for the treatment of urothelial, colorectal, lung, breast, and other solid malignancies. However, Nectin-4’s physiological expression in epidermal keratinocytes restricts the utility of potent immunotherapeutic strategies such as bispecific T cell engagers (TCEs) and chimeric antigen receptor T cells (CAR-Ts), due to on-target, off-tumor toxicity. CT-202 is a fully humanized, dual pH-dependent Nectin-4 x CD3 bispecific TCE engineered to widen the therapeutic window by selectively targeting Nectin-4 and CD3 within the acidic tumor microenvironment (TME). Methods: CT-202 was characterized for pH-dependent binding to both Nectin-4 and CD3, employing in vitro affinity assays across pH gradients mimicking physiological (pH 7.4) and tumoral (pH ∼6.5) conditions. In vivo pharmacology and safety assessments were performed in non-human primates comparing CT-202 and non-pH-dependent bispecific controls. In vitro functional assays, including cytotoxicity and cytokine release, were used to determine dose-response relationships to inform initial human dosing strategies. Results: CT-202 demonstrated high affinity and specificity for Nectin-4 and CD3 exclusively at the lower pH characteristic of the TME; at neutral pH, binding was markedly attenuated. This conditional dual engagement was essential for effective T cell-mediated cytotoxicity against tumor targets in vitro. In non-human primate toxicology studies, CT-202 exhibited a >30-fold improvement in the Highest Not Severely Toxic Dosage (HNSTD) relative to traditional bispecifics lacking pH modulation, delineating a superior safety profile. Integrated analysis of in vitro potency and in vivo toxicology data supported a rational selection of starting dose for forthcoming clinical investigation. Conclusion: CT-202 represents a novel dual pH-selective bispecific TCE targeting Nectin-4 x CD3, designed to optimize tumor selectivity and minimize off-tumor toxicity. Preclinical data validate the differentiated pharmacological and safety attributes of this modality, justifying its advancement to first-in-human Phase 1 trials. This approach highlights the potential of dual pH-dependent bispecific antibodies as a next-generation platform for the selective immunotherapy of Nectin-4-expressing solid tumors.​ Citation Format: Stanley Roberts, Kelly Byrnes-Blake, Heather Ansorge, Eric Butz, Daniel Olson. Targeting solid tumors with pH-dependent dual-specific TCEs: First-in-human development of CT-202 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 5392.

Zika virus (ZIKV), dengue virus (DENV) and chikungunya virus (CHIKV) are arboviruses transmitted by Aedes mosquitoes. While DENV serotypes 1 and 2 (DENV1 and DENV2) are the most prevalent in Guatemala, serotypes 3 and 4 (DENV3 and DENV4) have caused recent epidemics. In 2024, a public health emergency was declared by the Ministry of Health due to the rise in dengue cases. CHIKV and ZIKV outbreaks were reported between 2014-2017.Evolution of flavivirus serostatus among the AGRI cohort (2020-2022) The graph shows the serologic characteristics of the AGRI cohort against flavivirus infections. A rise in the multytipic DENV serostatus is observed over the years. On the contrary, there is a decline in the flavivirus-naive population.Density distribution of the MFI values against arbovirus-specific antigens The MFI of the antigen-antibody reaction was recorded for each arbovirus. The evolution of cohort-level mean fluorescence intensity (MFI) readings over 3 years is shown. Positivity cutoffs are indicated by the dashed red line. Mean Fluorescence Intensity (MFI) from anti-CHIKV/ZIKV/DENV1-4 antibodies was obtained using an IgG-based multiplex bead assay. Flavivirus-specific beads were coupled with the EDIII protein of ZIKV/DENV1-4. CHIKV beads were coupled with CHIKV E2 protein. We tested 1136 samples from 478 individuals, collected in 2020 (n=478), 2021 (n=338) and 2022 (n=320). A set of 15 samples from children born between 2018-2022 were used as regionally appropriate samples to calculate the positivity cutoffs (mean MFI + 3SD). A previously described algorithm for analyzing flavivirus MFI signals was used to discriminate between naive samples and primary/multitypic infections. CHIKV seropositivity was 56.9%, 51.5% and 53.4% for 2020, 2021 and 2022. During the follow up, 12 individuals had a negative-to-positive seroconversion against CHIKV. For 2020, 2021, and 2022, we detected seropositivity for primary infections of DENV1 (16.9%, 9.17%, 10.6%), DENV2 (9.41%, 21.0%, 11.2%), DENV3 (1.88%, 0.30%, 0.00%) and ZIKV (11.9%, 6.51%, 4.38%). Naïve-to-primary seroconversions were found for DENV1 in 2022 (n=12), for DENV2 in 2021 (n=14) and 2022 (n=10), and for ZIKV in 2021 (n=1) and 2022 (n=3). Flavivirus-naive prevalence went from 15.7% in 2020 to 7.8% in 2022. Though confirmatory testing is needed, these findings suggest that active DENV1/2, ZIKV and CHIKV transmission was ongoing in the region for this period. Blair Weikel, MPH, Merck: Grant/Research Support Molly Lamb, PhD, Merck: Grant/Research Support Daniel Olson, MD, Fundacion para la Salud Integral de los Guatemaltecos: Board Member|Merck: Grant/Research Support|Roche Diagnostics: Grant/Research Support

Vector-borne pathogens, which are transmitted by blood-feeding arthropods to animals and people, are common in tropical regions where, combined with economic factors, can cause significant public health burden. A community-level study was undertaken in southwestern Guatemala to assess the presence of vector-borne pathogens in blood samples from humans (n = 98), their animals (n = 90), and ectoparasites (n = 83) over a period of 2 weeks. Human capillary blood was collected from participant's index finger, and animal venous blood (chickens, pigs, dogs, and cats) was collected from the jugular or cephalic veins at the enrollment period of a concurrent study. Ectoparasites (fleas, ticks, and lice) were collected from dogs at the time of the blood collection. Total DNA was extracted from the human blood, animal blood, and ectoparasites and assayed using published PCR assays for Anaplasma spp., Bartonella spp., and Ehrlichia spp. Ectoparasites were also tested for the presence of Rickettsia spp. DNA by PCR. Anaplasma spp. DNA was amplified from 1 of 39 (2.6 %) chickens and 1 of 6 (16.6 %) turkeys. All human and dog blood samples were negative for Bartonella spp. in the same community. Ehrlichia spp. DNA was amplified from 12 (60 %) of 20 dogs and sequencing documented Ehrlichia spp. in 2 dogs and the ticks and fleas collected from these dogs. All the Ehrlichia spp.-positive sequences showed 100 % homology to E. canis sequences and other uncultured Ehrlichia spp. strains isolated from animals. Rickettsia spp. DNA was not amplified from any of the ectoparasites assessed. Our findings suggest that Ehrlichia spp. are common in dogs and Anaplasma spp. are circulating in poultry in a rural community in southwest Guatemala. We expect these results to be used in awareness campaigns and public health interventions to reduce vector borne pathogens in the region.

Ewing sarcoma and osteosarcoma constitute 36% of all primary bone cancers. However, these 2 subtypes represent the most commonly diagnosed bone cancer types in the pediatric and adolescent population. Although still largely unknown, certain genetic mutations, rearrangements, and/or predisposition syndromes likely play a role in the pathogenesis of bone cancer. Osteosarcoma may also develop as a direct result of the long-term side effects of radiation therapy. With the implementation of a multimodality approach to treatment, including multiagent neoadjuvant and adjuvant chemotherapy regimens, targeted therapy options, surgery, and radiation, individuals with Ewing sarcoma and osteosarcoma are showing higher cure rates and improved overall survival. The NCCN Guidelines for Bone Cancer provide a consensus and evidence-based framework for the workup, management, and surveillance of local and recurrent/metastatic disease.

BACKGROUND:Prenatal Zika virus (ZIKV) infection leads to microcephaly and adverse neurodevelopment. The effects of postnatal ZIKV infection on the developing brain are unknown. We assessed the neurodevelopmental outcomes of children exposed postnatally during the ZIKV epidemic. METHODS:A prospective study enrolled infants 0-3 months of age and their mothers, and children 1.5-3.5 years of age in rural Guatemala from 2017 and were followed for 12 months until 2019. Neurodevelopment was evaluated using the Mullen Scales of Early Learning (MSEL). ZIKV and dengue virus (DENV) infections were identified by polymerase chain reaction (PCR) using active surveillance. Serological analyses, stratified by age group flavivirus serostatus at enrollment, were conducted using a focus reduction neutralization test. RESULTS:Of 1371 enrolled participants, 1187 (86.6%) completed the study. No PCR-confirmed ZIKV infections were identified during the study period. One-third of 1.5-3.5-year-old children were ZIKV-seropositive at enrollment (likely postnatal infection). Twenty participants (5.8%) tested positive for DENV by PCR (11 infants, 5 children and 4 mothers); 15 (75%) were DENV-3 infections and 5 were DENV-2. The incidence of DENV infection in infants was 2.6%. No significant differences in MSEL scores were found between infants born seropositive versus seronegative for ZIKV or DENV. DENV seropositivity at enrollment in 1.5-5-year-old children was associated with lower MSEL scores for fine motor, visual reception and language, and microcephaly at 12 months versus seronegative children (all P < 0.05). CONCLUSIONS:Postnatal ZIKV infection in children from rural Guatemala was not associated with worse neurodevelopmental outcomes. DENV seropositivity was associated with a higher risk of microcephaly in infants and worse neurodevelopmental outcomes in children.

Guatemala has one of the lowest coronavirus disease 2019 vaccination rates in the Americas, with rural communities experiencing disproportionately low coverage. A 2021-2022 vaccine knowledge and behaviors survey of households in a rural community in southwest Guatemala revealed that access was a significant barrier, particularly among women and those who did not work outside the home. For the present study, a follow-up survey was conducted in 2023 to assess changes in vaccine access, hesitancy, and motivations. Both surveys were completed by 199 people. Among those eligible for vaccination at enrollment, the proportion vaccinated increased from 47% to 77%. The primary motivations for vaccination remained protecting family and friends, although concern for personal health increased. Regression models did not identify significant predictors of vaccine uptake, although household size approached significance. The findings highlight the importance of ongoing efforts to improve vaccine access and information, particularly in addressing the significant proportion of individuals who are uncertain about their motivations for vaccination.

BACKGROUND:Multiplex polymerase chain reaction panels improve outcomes for bloodstream infections in high-income countries, but little is known in low- and middle-income countries, where there are high rates of antimicrobial resistance and mortality. METHODS:We conducted a pragmatic clinical trial in children at a public hospital in Guatemala comparing the impact of a multiplex polymerase chain reaction panel to conventional microbiologic methods. The BioFire Blood Culture Identification (BCID2) panel was performed with antimicrobial stewardship advice on positive blood cultures from midnight to 1 pm on weekdays as the intervention. Children with positive cultures outside these times served as the control group. Time-to-optimal antimicrobial therapy was the primary outcome measure. All-cause mortality was a secondary outcome. RESULTS:A total of 246 children were enrolled from April 2022 to October 2022: 135 in the BCID2 and 111 in the control group. The most common pathogens were coagulase-negative Staphylococcus (54%) and Klebsiella pneumoniae (11%). There was a significant reduction in median time-to-optimal antimicrobial therapy from 97·9 (0-252.3) hours to 31·5 (0-157.1) hours ( P = 0.03) in the control versus BCID2 groups. There was a trend for reduction in overall mortality from 18% (20 deaths) in the control to 10% (14 deaths) in the BCID2 group ( P =0.08). Subanalysis of children with Gram-negative sepsis revealed a 62% reduction in mortality with 14 (25%) deaths in the control group compared with 4 (9·5%) deaths in the BCID2 group ( P = 0.05). CONCLUSIONS:Use of BCID2 with antimicrobial stewardship significantly reduces time-to-optimal antimicrobial therapy in low- and middle-income countries like Guatemala, with a significant reduction in mortality due to Gram-negative bacteremia.

Urinary antigen detection (UAD) assays can address diagnostic challenges with culture-based identification of S. pneumoniae. We aimed to evaluate the utility of Pfizer’s UAD1 and UAD2 assays for pneumococcal serotype surveillance in children with community acquired pneumonia (CAP) or upper respiratory tract infections (URI). From March 2021–December 2023, children 3 months to 5 years who presented to the Children’s Hospital Colorado Emergency Department with respiratory symptoms were enrolled as CAP or URI; healthy children served as controls. Nasal swabs were tested for pneumococcus by PCR. UAD assays identified pneumococcal serotypes from urine. Groups were compared using descriptive statistics. We enrolled 407 controls, 202 with URI, and 280 with CAP. Positivity thresholds were set for all UAD serotypes. Pneumococcal nasal swab positivity was 23

TPS844 Background: Patients with advanced gastrointestinal (GI) malignancies have poor prognoses and limited treatment options. Cadherin 17 (CDH17) is a cell membrane-associated protein important for GI cell-cell interactions that is expressed in proximity to epithelial tight junctions. In some GI malignancies, CDH17 expression is also expressed diffusely across the cancer cell membrane, thus providing access to CDH17 directed CAR T-cells. CHM CDH17 is a third generation autologous CAR T-cell product candidate that was designed to target and eradicate CDH17+ solid tumors. Notably, expression of CDH17 varies across indications in the cancer setting CDH17– TABLE 1. Methods: Clinical Trial NCT06055439 is a seamless Phase 1/2 clinical trial of autologous CHM CDH17 CAR T-cells for patients with advanced gastric cancer (GC), colorectal (CRC) cancer or neuroendocrine tumors (NETs) of the midgut or hindgut. As CDH17 expression in GC is heterogenous, GC subjects will be screened for CDH17 expression. In preparation for receiving CDH17 CAR T-cells, subjects receive 3-days of lymphodepleting intravenous (IV) chemotherapy (fludarabine and cyclophosphamide). The Phase 1 portion of the clinical trial uses a 3+3 dose escalation and a starting dose of 50 million CAR-T cells in a single IV infusion. Decisions regarding dose escalation/de-escalation are based on real-time dose-limiting toxicity evaluation during the first 28 days of treatment during dose escalation. After establishing a recommended Phase 2 dose, three indication-specific Simon 2-Stage cohorts will be initiated in (1) GC (2) CRC and (3) NETs of the midgut or hindgut to further characterize the safety and assess the efficacy of CHM CDH17 CAR T-cells. This is an ongoing first-in-human multi-center clinical trial of CHM CDH17, a CDH17 directed autologous CAR T-cell product candidate, enrolling subjects with advanced GI cancers that express CDH17. Clinical trial information: NCT06055439 . Expression of CDH17 in selected gastrointestinal cancer indications. Indication Sample size CDH17Expression %* Colorectal cancer 821 96% Neuroendocrine tumors of the midgut and hindgut 119 97% Gastric cancer 1,409 64% *Expression of total tumors tested for CDH17 by immunohistochemistry (CHM data on file).

We evaluated the performance of saliva compared with nasopharyngeal (NP) swabs for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza A/B, and respiratory syncytial virus (RSV) using the Roche cobas® Liat® point-of-care platform (Roche, Basel, Switzerland). Within an existing adult cohort in Guatemala, consenting participants with influenza-like illness (ILI) provided paired saliva and NP swabs, which were tested for SARS-CoV-2, influenza A/B, and RSV on the Liat platform. Among 138 ILI episodes from 123 enrolled subjects, 35/124 (28.2%), 5/135 (3.7%), 6/135 (4.4%), and 7/135 (5.2%) samples were reverse transcription polymerase chain reaction-positive for SARS-CoV-2, influenza A, influenza B, and RSV, respectively. For SARS-CoV-2, saliva/NP agreement was 90.3% (Cohen's kappa = 0.731); 12 (9.7%) of the samples were discordant (three saliva-positive only, nine NP-positive only); and the median cycle threshold (Ct) for saliva was higher than that for NP (26.53 versus 23.54; P = 0.005). In our setting, saliva had a lower viral load correlate (Ct) but maintained a good correlation with NP swabs for the detection of SARS-CoV-2 on the Liat platform.

We explored social, demographic, and health risk factors for occipitofrontal circumference (OFC) growth in infants living in a rural, low-resource region of Guatemala. OFC was measured at enrollment (0.1–2.9 months of age) and one year later (11.5–16.1 months of age) for 430 infants participating in a prospective cohort study conducted between 2017 and 2019. Potential predictors were collected at enrollment or were measured during the year of the study. We performed a two-stage risk factor analysis, using univariate regression modeling to identify potential risk factors, followed by multivariable regression modeling to identify independent, significant risk factors for smaller OFC at birth and 1 year in this low resource setting. Mean OFC at enrollment was -0.4 (1.2) and at 1 year was -1.1 (0.9). Probable zika exposure in utero and shorter maternal height were independently, significantly associated with smaller OFC at both enrollment and 1 year. Exposure to cigarette smoking in utero was independently significantly associated with smaller OFC at enrollment. Infant complications at birth, microcephaly at enrollment and stunting at enrollment were also independently significantly associated with smaller OFC at 1 year (all p-values < 0.05). No exposures measured during the study were associated with OFC at 1 year. All the independent predictors of small OFC during the study period were present at enrollment (within the first 3 months of life), including maternal height, and smoking and ZIKV exposure during pregnancy. Exposures after the first three months of life were not predictive of OFC at one year. Continued work to identify specific risk factors and develop targeted prevention programs is warranted. The prevalence of microcephaly and poor occipitofrontal (OFC) growth may be higher in lower- and middle-income countries than in high-income countries, although the reasons for this are not known. Maternal height and previous zika exposure were associated with smaller OFC at both enrollment and 1 year later, while exposure to cigarette smoking in utero was associated with smaller OFC at enrollment. Infant complications at birth, microcephaly and stunting at enrollment were also independently significantly associated with smaller OFC at 1 year. Targeted interventions may reduce the prevalence of microcephaly and poor OFC growth, with related benefits in child neurodevelopment.

The NCCN Guidelines for Cutaneous Melanoma (termed Melanoma: Cutaneous) provide multidisciplinary recommendations for diagnostic workup, staging, and treatment of patients. These NCCN Guidelines Insights focus on the update to neoadjuvant systemic therapy options and summarize the new clinical data evaluated by the NCCN panel for the recommended therapies in Version 2.2024 of the NCCN Guidelines for Cutaneous Melanoma.