Research into the developmental origins of, and lifecourse influences on, health and disease has a significant gap: infections. Clinical and subclinical infections are nearly universal in early life and can induce structural and functional changes in developing organ systems with life-long consequences. Emerging evidence links common childhood infections-such as Epstein-Barr virus, Cytomegalovirus and Helicobacter pylori-to so-called non-communicable diseases ranging from respiratory to neurodevelopmental and cardiometabolic diseases. Identifying infectious determinants of non-communicable diseases offers substantial opportunities for prevention and early intervention. We describe a newly developed infectious data resource within the EU Child Cohort Network, designed to enable triangulation of evidence on the impact of early life infections on children's health and long-term trajectories of disease. The network established in 2017, currently brings together 37 pregnancy and childhood cohorts from 16 predominantly European countries and follows over 300,000 children and their families from pregnancy through childhood and, in many cohorts, into adulthood. Cohorts include a comprehensive set of harmonized variables covering health and disease phenotypes (cardiometabolic, respiratory, and mental) that are also well-established early indicators of later-life non-communicable disease risk. Building upon this, we present here the extensive infections data available in the cohorts ranging from questionnaires and registries to serological measurements for more than 20 pathogens. Harmonizing and integrating infection data within the EU Child Cohort Network supports a shift from viewing infections solely as causes of acute disease towards recognising them as integral components of the early-life exposome and potential determinants of lifelong health trajectories.

Acute appendicitis within a Spigelian hernia is a rare clinical entity that may present with atypical symptoms, resulting in diagnostic delay and complex operative decision-making. Previously reported cases have most commonly presented with localized right lower quadrant pain, abdominal wall masses, incarceration, bowel obstruction, or strangulation. Spigelian hernias occur along the semilunar line and may contain intra-abdominal structures, including the appendix, resulting in non-classic symptoms of appendicitis. We report a case of a 52-year-old woman with a history of cerebrovascular accident with residual left-sided weakness, prior laparotomy and colostomy following a gunshot wound to the left lower quadrant (2012), and atrial fibrillation with poor adherence to apixaban, who presented with progressive bilateral lower extremity pain and right lower quadrant pain radiating to the groin, with the atypical lower extremity symptoms initially prompting neurologic and musculoskeletal evaluation and delaying recognition of the underlying abdominal pathology. Initial vital signs were notable for mild tachycardia, and laboratory evaluation demonstrated mild leukocytosis. Over approximately one month, her progressive lower extremity pain was initially attributed to neurologic or musculoskeletal pathology, resulting in nondiagnostic spinal imaging before CT of the abdomen and pelvis established the diagnosis. CT imaging of the abdomen and pelvis ultimately revealed a right Spigelian hernia containing an inflamed appendix, consistent with acute appendicitis within the hernia sac. She underwent robotic appendectomy and hernia repair with mesh placement. Intraoperatively, a suppurative appendix within a 4-cm Spigelian hernia was confirmed. Her postoperative course was complicated by a superficial fluid collection managed with intravenous clindamycin and piperacillin-tazobactam for three days, with subsequent clinical improvement. This case is notable for the atypical presentation and resulting diagnostic delay. It highlights the importance of considering abdominal wall hernias and anatomic displacement of intra-abdominal structures in patients with persistent groin or lower quadrant pain, particularly when neurologic or musculoskeletal evaluation is unrevealing. Cross-sectional imaging remains essential for identifying uncommon hernia-related causes of appendicitis.

Individuals with prenatal alcohol exposure (PAE) and fetal alcohol spectrum disorders (FASDs) present a range of neurodevelopmental deficits (e.g., inattention, hyperactivity, and executive dysfunction) which have shown marked overlap with attention-deficit/hyperactivity disorder (ADHD), making differential diagnosis challenging. While rates of comorbidity are high, evidence has suggested there are important distinctions between neurodevelopmental phenotypes. To understand these distinctions, we evaluated whether proposed neurobehavioral disorder associated with prenatal alcohol exposure (ND-PAE) criteria in the appendix of the Diagnostic and Statistical Manual for Mental Disorders (Fifth Edition) can differentiate FASD from ADHD. We conducted systematic searches across three databases (Medline, PsycINFO, PubMed) to identify studies comparing behavioral and cognitive functioning between FASD, ADHD, and healthy controls (HCs). Outcomes indicated FASD individuals have greater magnitude neurodevelopmental deficits than ADHD; however, no differences were found regarding the pattern of deficit because of methodological limitations, such as low I[2]. Moreover, outcomes supported adaptive and neurocognitive (executive functioning) criteria but did not support self-regulation criteria. These findings collectively underscore a need for clinicians to consider the magnitude of deficits presented to facilitate accurate recognition of PAE. Further research characterizing ND-PAE criteria and differences in the magnitude of deficits between disorders may ultimately support more accurate differential diagnosis.

The caecum normally descends to the right iliac fossa during embryogenesis. Disruptions in midgut development may result in its atypical positioning. In a male cadaver, the small, conical caecum and paracaecal appendix were in the right lumbar region. The ileocaecal orifice was on the anterior caecal wall, and the appendicular orifice opened on the medial caecal wall inferior to it. The ascending colon was short, and the hepatic flexure was inferior to hepatic quadrate lobe. The right colic artery was absent. The ascending branch of the ileocolic artery supplied the caecum, and the appendix. The disposition of the rest of the intestinal tract and peritoneum were observed, and measurements were taken. Midgut development involves multiple regulatory genes, signalling pathways, transcription factors and mesenchyme-endoderm cross-talk. Mutations in several candidate genes were identified as contributing to midgut malrotation. Awareness of such a rare anatomical variation is essential to avoid misdiagnosis of atypical appendicitis or intestinal obstruction.

This study investigates the instructional practices and self-reported confidence of educators working with Deaf Multilingual Learners (DMLs), students who are deaf or hard-of-hearing and come from homes where languages other than English or American Sign Language are used. Through a national web-based survey (Appendix A), data were collected from 89 current and former teachers of DMLs, capturing their demographic profiles, instructional strategies, and perceptions of their ability to support language development. Quantitative analyses, including descriptive statistics, t-tests, and correlation analyses, were conducted to identify patterns related to teaching experience, strategy use, and support systems. Findings show that multimodal strategies, such as combining signs, spoken language, visuals, and print, were widely used and rated highly by educators, particularly those with more than 3 years of experience. In contrast, strategies that incorporated students' home languages were used infrequently. Use of phonological awareness strategies varied depending on the instructional language modality, with fingerspelling and signed-language scaffolds used more often than spoken phonics-based strategies. Notably, gaps emerged in access to DML-specific training and collaboration opportunities, and most respondents identified as White, female, and English-speaking, highlighting a lack of educator diversity. These findings underscore the importance of targeted professional development in multimodal and phonological instruction, culturally responsive pedagogy, and home language inclusion. Addressing these gaps is essential to improving equitable language access and educational outcomes for DMLs in K-12 settings. Appendix A showcases the questions from the survey (See Appendix A).

[Box: see text]Living guidelines are developed for selected topic areas with rapidly evolving evidence that drives frequent change in recommended clinical practice. Living guidelines are updated on a regular schedule by a standing expert panel that systematically reviews the health literature on a continuous basis, as described in the ASCO Guidelines Methodology Manual. ASCO Living Guidelines follow the ASCO Conflict of Interest Policy Implementation for Clinical Practice Guidelines. Living Guidelines and updates are not intended to substitute for independent professional judgment of the treating clinician and do not account for individual variation among patients. See appendix for disclaimers and other important information (Appendix I and Appendix II). Updates are published regularly and can be found on the ASCO Publications website.

[Box: see text]Living guidelines are developed for selected topic areas with rapidly evolving evidence that drives frequent change in recommended clinical practice. Living guidelines are updated on a regular schedule by a standing expert panel that systematically reviews the health literature on a continuous basis, as described in the ASCO Guidelines Methodology Manual. ASCO Living Guidelines follow the ASCO Conflict of Interest Policy Implementation for Clinical Practice Guidelines. Living Guidelines and updates are not intended to substitute for independent professional judgment of the treating clinician and do not account for individual variation among patients. See appendix for disclaimers and other important information (Appendix I and Appendix II). Updates are published regularly and can be found on the ASCO Publications website.

We present a 55‑year‑old woman with adnexal masses and elevated CEA. Malignancy workup, adnexal biopsy, and intraoperative assessment revealed the appendix as the primary site, with pathology confirming mucinous adenocarcinoma. While mucinous tumors often show limited avidity on 18F‑FDG PET/CT due to low cellularity, this case demonstrates the utility of fibroblast activation protein inhibitor (FAPI) imaging. 99mTc‑FAPI SPECT/CT successfully identified widespread skeletal metastases, initially detected on bone scan, and extensive soft‑tissue involvement in the peritoneum, appendiceal region, and pleura, highlighting its potential as a superior staging modality for mucinous neoplasms and suggesting the feasibility of FAPI‑targeted theranostics in advanced disease.

Complicated appendicitis, in which the appendix has perforated, is a well-studied pediatric surgical condition. Despite this, practice management varies widely among institutions. Both suspected and confirmed perforation present unique challenges beyond those of acute uncomplicated appendicitis, namely increased healthcare utilization and a higher incidence of postoperative abscess. Debate continues regarding the role and timing of appendectomy, as well as antibiotic choice and duration to mitigate these challenges. There are developing new initiatives that target different aspects of management in the hopes of reducing overall morbidity and sequela. In this article, we discuss the history and current management of complicated appendicitis in children, along with emerging developments in the field.

Ultrasonography is particularly useful in children because it can be repeated without ionizing radiation and can be adapted to the clinical question during the examination. A 10-year-old boy with right lower quadrant pain, right leg pain, and a limp was referred with suspected acute appendicitis. A comprehensive diagnostic ultrasound examination of the abdomen demonstrated a normal appendix and an enlarged lymph node corresponding to the site of right lower quadrant tenderness. During the examination, conversation with the patient and his mother disclosed household cat ownership, frequent exposure to cat fleas, and multiple flea bites. The abdominal findings, exposure history, and pre-existing right leg symptoms were shared with the clinical team. At the physician's request, additional ultrasound evaluation of the right popliteal region demonstrated a second enlarged, tender lymph node. Superb microvascular imaging showed nonspecific vascular signals predominantly near the hila of both nodes. Serologic and molecular testing for Bartonella henselae was not performed; therefore, cat-scratch disease remained a clinical suspicion rather than a confirmed diagnosis. After azithromycin treatment, the symptoms improved and both lymph nodes decreased in size on follow-up ultrasonography. This case does not establish an ultrasonographic diagnosis of cat-scratch disease. Rather, it illustrates how ultrasonography provided anatomic correlates for symptoms at two sites, complemented the information available from clinical assessment alone, and supported noninvasive follow-up.

In 2023, international consensus recommendations suggested the use of prolonged-infusion beta-lactam antibiotics over short-infusion dosing in severely ill adult patients to improve mortality or clinical cure, although the certainty of evidence was very low. With the availability of several new randomized controlled trials (RCTs), this focused update re-evaluates the efficacy of prolonged versus short infusion among severely ill adult patients. The original Population, Intervention, Comparator, and Outcome (PICO) question VII was separated into two questions addressing mortality (VIIa) and clinical cure (VIIb). Methods used for study identification, screening, and evidence grading were consistent with the original guideline, with the addition of Bayesian meta-analyses. A total of 28 RCTs evaluating mortality in severely ill adults were analyzed, with pooled estimates favoring prolonged infusion (RR 0.91; 95% confidence interval 0.85 to 0.97), supported by Bayesian analyses demonstrating a 98.76% posterior probability of benefit. Across 21 RCTs evaluating clinical cure, prolonged infusion improved outcomes compared with short infusion (RR 1.11; 95% confidence interval 1.06 to 1.17), supported by Bayesian analyses demonstrating a 99.97% posterior probability of benefit. Certainty of evidence was strengthened to moderate for mortality and low for clinical cure. Consistent with the original recommendation (PICO X), subgroup analyses evaluating loading doses suggested improved outcomes when a loading dose is used before continuous infusion. Overall, the cumulative evidence reinforces and strengthens the recommendation for use of prolonged-infusion beta-lactam therapy in severely ill adult patients to improve survival and clinical cure. Continued use of loading doses when initiating continuous-infusion therapy is suggested. Future research should identify subpopulations most likely to benefit, clarify optimal prolonged-infusion strategies, and define the role of therapeutic drug monitoring.