Effect of maternal prebiotic supplementation on human milk immunological composition: Insights from the SYMBA study.

BACKGROUND: Immunomodulatory proteins in human milk (HM) can shape infant immune development. However, strategies to modulate their levels are currently unknown. This study investigated whether maternal prebiotic supplementation alters the levels of immunomodulatory proteins in HM. METHODS: The study was nested within the SYMBA double-blind randomized controlled trial (ACTRN12615001075572), which investigated the effects of maternal prebiotic (short-chain galacto-oligosaccharides/long-chain fructo-oligosaccharides) supplementation from <21 weeks gestation during pregnancy until 6 months postnatal during lactation on child allergic disease risk. Mother-child dyads receiving prebiotics (n = 46) or placebo (n = 54) were included in this study. We measured the levels of 24 immunomodulatory proteins in HM collected at 2, 4, and 6 months. RESULTS: Cluster analysis showed that the overall immunomodulatory protein composition of milk samples from both groups was similar. At 2 months, HM of prebiotic-supplemented women had decreased levels of TGF-ß1 and TSLP (95% CI: -17.4 [-29.68, -2.28] and -57.32 [-94.22, -4.7] respectively) and increased levels of sCD14 (95% CI: 1.81 [0.17, 3.71]), when compared to the placebo group. At 4 months, IgG1 was lower in the prebiotic group (95% CI: -1.55 [-3.55, -0.12]) compared to placebo group. CONCLUSION: This exploratory study shows that prebiotic consumption by lactating mothers selectively alters specific immunomodulatory proteins in HM. This finding is crucial for understanding how prebiotic dietary recommendations for pregnant and lactating women can modify the immune properties of HM and potentially influence infant health outcomes through immune support from breastfeeding.

Informal carer involvement in the transition of medicines-related care for patients moving from hospital to home: a realist review protocol.

INTRODUCTION: Transition of care for a patient between hospital and home can cause disruption to normal routines, increasing the risk of medicines-related harm. The transition from hospital to home is more complex when a patient does not self-manage their medicines but relies on an informal or unpaid carer (eg, spouse, family member or friend) to provide support. Given the day-to-day medicines-related support provided by informal carers, there is a need to understand how informal carers manage the transition of care from hospital to home; what aspects of hospital discharge act as barriers and facilitators to their involvement and when, how and why these impact patients. METHODS AND ANALYSIS: A realist review will be undertaken to develop a programme theory. The programme theory will theorise which medicines-related interventions are useful to carers, and how they are useful. It will outline what aspects of those interventions are the most useful and why, and how context influences engagement and medicine-related outcomes. The review will be reported in line with the Realist and Meta-narrative Evidence Syntheses: Evolving Standards guidelines. Data will be selected, screened and extracted based on defined inclusion and exclusion criteria and relevance to the developing programme theory with the involvement of at least two authors acting independently. Inclusion criteria relate to the relevance to hospital discharge where patients move back to their home, where a carer is involved and where interventions relate to medicines use. Searches will be conducted in PubMed, CINAHL (via EBSCOhost) and EMBASE databases (see supplementary materials for a draft search strategy).Patients and public, participation, involvement and engagement (PPIE) will be incorporated into all stages of the review through iterative engagement and discussion with patient, carers and representatives from carer organisations. The review will follow four steps: (1) development of the initial programme theory, (2) evidence search, (3) selection, extracting, and organising data and (4) synthesising evidence and drawing conclusions.Informal carer involvement in transitions of care is a complex and varied phenomena. The programme theory will be shaped by sustained PPIE reflecting the priorities and experiences of lived experience. The realist review be progressively focused so we can develop a better understanding of carer involvement in patient transitions when moving from hospital to home relating to medicines use. ETHICS AND DISSEMINATION: Ethical approval is not required. The findings of the review will be disseminated via journal articles and through patient and public facing resources such as a visual patient-public-carer focused summary. PROSPERO REGISTRATION NUMBER: CRD42021262827.

Effects of social dominance and acute social stress on morphology of microglia and structural integrity of the medial prefrontal cortex.

Chronic stress increases activity of the brain's innate immune system and impairs function of the medial prefrontal cortex (mPFC). However, whether acute stress triggers similar neuroimmune mechanisms is poorly understood. Across four studies, we used a Syrian hamster model to investigate whether acute stress drives changes in mPFC microglia in a time-, subregion-, and social status-dependent manner. We found that acute social defeat increased expression of ionized calcium binding adapter molecule 1 (Iba1) in the infralimbic (IL) and prelimbic (PL) and altered the morphology Iba1+ cells 1, 2, and 7 days after social defeat. We also investigated whether acute defeat induced tissue degeneration and reductions of synaptic plasticity 2 days post-defeat. We found that while social defeat increased deposition of cellular debris and reduced synaptophysin immunoreactivity in the PL and IL, treatment with minocycline protected against these cellular changes. Finally, we tested whether a reduced conditioned defeat response in dominant compared to subordinate hamsters was associated with changes in microglia reactivity in the IL and PL. We found that while subordinate hamsters and those without an established dominance relationships showed defeat-induced changes in morphology of Iba1+ cells and cellular degeneration, dominant hamsters showed resistance to these effects of social defeat. Taken together, these findings indicate that acute social defeat alters microglial morphology, increases markers of tissue degradation, and impairs structural integrity in the IL and PL, and that experience winning competitive interactions can specifically protect the IL and reduce stress vulnerability.

Physicians' knowledge, attitudes, and practices regarding fibromyalgia: A systematic review and meta-analysis of cross-sectional studies.

BACKGROUND: The diagnosis, etiology, and optimal management of fibromyalgia remains contentious. This uncertainty may result in variability in clinical management. We conducted a systematic review and meta-analysis of cross-sectional studies examining physicians' knowledge, attitudes, and practices regarding fibromyalgia. METHODS: We searched MEDLINE, Embase, and PubMed from inception to February 2023 for cross-sectional surveys evaluating physicians' attitudes toward, and management of, fibromyalgia. Pairs of independent reviewers conducted article screening, data extraction, and risk of bias assessment in duplicate. We used random-effects meta-analysis to pool proportions for items reported by more than one study and the Grading of Recommendations Assessment, Development, and Evaluation approach to summarize the certainty of evidence. RESULTS: Of 864 citations, 21 studies (8904 participants) were eligible for review. Most physicians endorsed fibromyalgia as a distinct clinical entity (84%; 95% confidence interval [CI], 74-92), and half (51%; 95% CI, 40-62) considered fibromyalgia a psychosocial condition. Knowledge of formal diagnostic criteria for fibromyalgia was more likely among rheumatologists (69%, 95% CI, 45-89) versus general practitioners (38%, 95% CI, 24-54) (P = .04). Symptom relief was endorsed as the primary management goal by most physicians (73%, 95% CI, 52-90). Exercise, physiotherapy, antidepressants, nonsteroidal anti-inflammatory drugs, and non-opioid analgesics were most endorsed for management of fibromyalgia, but with wide variability between surveys. Opioids and most complementary and alternative interventions (e.g., homeopathy, chiropractic, and massage) received limited endorsement. CONCLUSION: There is moderate certainty evidence to suggest that physicians are divided regarding whether fibromyalgia is a biomedical or psychosocial disorder. Physicians typically prioritize symptom relief as the primary goal of management, and often endorse management with exercise, non-opioid analgesics, nonsteroidal anti-inflammatory drugs, antidepressants, and physiotherapy (moderate to high certainty evidence); however, important practice variation exists.

Four Decades of Research Productivity and Hot Spots in Pancreas Transplantation.

Background: The field of pancreas transplantation has undergone transformative phases, progressing from its promising inception in 1966 to becoming a standard treatment for patients with insulin-dependent diabetes. This bibliometric analysis explores the progression of pancreas transplantation research over a period of four decades, mapping milestones, contributors, and emerging trends. Methods: Our bibliometric analysis utilizes the comprehensive Scopus database, which includes publication titles, author information, affiliations, abstracts, keywords, and journal details. The search strategy was centered on research related to pancreas and pancreas-kidney transplantation. The analysis encompasses the time frame spanning from 1983 to 2023, with the data extraction taking place on October 7th, 2023. Results: The analysis of 4,897 articles uncovered unique trends in the field of pancreas transplantation research. The years 1989, 1996, and 2021 saw significant increases in the number of publications, which corresponded to the responses to clinical challenges and advancements. Contributions by authors from the United States of America were the most numerous, with 1,905 publications and 49,949 citations. The research topics were highlighted by keywords such as "graft survival," "graft rejection," and" Immunosuppressive treatment." Conclusion: The fluctuations in publication trends that have been identified indicate dynamic reactions to changing priorities and challenges. Although it has limitations, this analysis provides valuable insights for researchers, clinicians, and policymakers who are dealing with the complex field of pancreas transplantation literature. Further bibliometric research may advance our knowledge and direct future initiatives in this developing field.

Anti-CD7 allogeneic WU-CART-007 in patients with relapsed/refractory T-cell acute lymphoblastic leukemia/lymphoma: a phase 1/2 trial.

Relapsed/refractory T-cell acute lymphoblastic leukemia (ALL)/lymphoma (LBL) represent a significant unmet medical need. WU-CART-007 is a CD7-targeting, allogeneic, fratricide-resistant chimeric antigen receptor T cell product generated from healthy donor T cells. WU-CART-007 was evaluated in a phase 1/2 study with a 3 + 3 dose-escalation design followed by cohort expansion in relapsed/refractory T-ALL/LBL. Patients received one infusion of WU-CART-007 after standard or enhanced lymphodepleting chemotherapy. The primary objectives, to characterize safety and assess the composite complete remission rate, were met. Of 26 patients enrolled, 13 received the recommended phase 2 dose (RP2D) of 900 million cells of WU-CART-007 with enhanced lymphodepletion. The most common treatment-related adverse event was cytokine release syndrome (88.5%; 19.2% grade 3-4). Biochemical abnormalities consistent with grade 2 hemophagocytic lymphohistiocytosis were seen in one patient (3.8%). Grade 1 immune effector cell-associated neurotoxicity syndrome events (7.7%) and one grade 2 acute graft-vs-host disease event occurred. Grade 5 events (11.5%) were due to fungal infection and multi-organ failure. The composite complete remission rate was 81.8% among 11/13 patients evaluable for response at the RP2D. WU-CART-007 at the RP2D demonstrated a high response rate in patients with relapsed/refractory T-ALL/LBL and has the potential to provide a new treatment option. ClinicalTrials.gov registration: NCT04984356.

Correction: Re-examining the effects of drought on intimate-partner violence.

[This corrects the article DOI: 10.1371/journal.pone.0254346.].

Widespread haemorrhages in infants post-shunting (WHIPS): clinical features, risk factors and neuroimaging characteristics of a rare and under-recognised phenomenon.

PURPOSE: Infants undergoing CSF shunting procedures face a rare complication which we propose to rename "Widespread Haemorrhages in Infants Post-Shunting" (WHIPS) to better capture this unique phenomenon specific to infants undergoing CSF diversion. Our objective is to analyse the risk factors for WHIPS development and provide a detailed neuroradiological description of these haemorrhages. MATERIALS AND METHODS: A radiology information system (RIS) was searched using the search terms "shunt" and/or "catheter" and/or "drain" and/or "ventriculoperitoneal" and/or "VP" between September 2008 to January 2021 for patients < 12 months of age. Clinical data was compiled for each patient meeting the inclusion criteria. Included cases were reviewed by three radiologists for the presence of WHIPS with calculation of the bifrontal ratio and documenting haemorrhage number, morphology, location and lobar distribution. RESULTS: 51 patients met inclusion criteria, 8 WHIPS patients and 43 controls. There was a statistically significant correlation between a larger post-op head circumference and WHIPS (p = 0.04). WHIPS was associated with post-haemorrhagic hydrocephalus and post-infectious hydrocephalus (p = 0.009). WHIPS were identified in the cortico-subcortical regions, periventricular white matter, and deep white matter. Haemorrhages were either punctate, ovoid or confluent. Haemorrhages ranged from single to innumerable. CONCLUSIONS: WHIPS represent a rare and under-recognised complication of CSF shunting unique to the infantile population. We postulate deep and superficial medullary venous haemorrhage as an underlying mechanism related to disordered intracranial hydrodynamics which are exacerbated in the infantile population due to underdeveloped arachnoid granulations and a compliant skull.

Recognising dying in motor neurone disease: A scoping review.

INTRODUCTION: Timely identification of dying in motor neurone disease enables optimal care, yet we know that healthcare professionals can fail to recognise when death is approaching. Clinical factors help predict the end of life in other terminal conditions. Examining these principles in motor neurone disease would help guide more accurate recognition of this critical phase. AIM: To examine and map out what is known about dying in patients with motor neurone disease, and the recognition of dying by healthcare professionals. DESIGN: A scoping review was conducted following the Arksey and O'Malley methodological framework. DATA SOURCES: Four electronic databases (MEDLINE, Scopus, PsycINFO and CINAHL) and grey literature were searched on the 10th May 2023. Reference lists and citations were also reviewed. RESULTS: From 1512 articles, 13 studies were included. Dyspnoea, anxiety and pain were the most common symptoms associated with the dying phase. Worsening respiratory function, the development of specific new symptoms and deteriorating symptom control suggested approaching death. No studies reported changes in vital signs or biomarkers associated with dying. Barriers to the recognition of dying by healthcare professionals included a rapid and unpredictable terminal decline. CONCLUSIONS: Dying in motor neurone disease is associated with patterns of symptoms and signs, however evidence is limited compared with other terminal conditions and requires further exploration. The characteristic sudden and unpredictable terminal decline is a key barrier to recognition of dying by healthcare professionals. Optimising advance care planning is one approach to navigate these complex, unpredictable clinical situations.

Digital screens in community pharmacy for public health messaging; a mixed-methods study.

OBJECTIVES: An independent evaluation was undertaken to investigate the perceived impact of installing digital screens in a group of community pharmacies as an approach to provide public health messaging. METHODS: Community pharmacy staff were interviewed prior to screen installation to investigate experience and perceptions of conventional public health campaigns using written materials. Staff were interviewed after the digital screen installation to investigate their opinions of the installation and its impact on public health delivery in the pharmacy. Patients and public representatives were recruited to visit the pharmacies and asked to complete a survey about what they observed and thought about the public health messaging. Interviews were transcribed verbatim and thematically analysed. Surveys consisted of open, closed, and rating questions. The results of which were descriptively analysed. KEY FINDINGS: Community pharmacy staff found paper-based campaigns work-intensive and created paper wastage. The digital screen installation was received positively by pharmacy staff and patient, and public representatives found them eye-catching and engaging. Staff were unable to report any conversations with members of the public triggered by the screens, but the patient and public volunteers were able to recall some of the health messages. CONCLUSIONS: Digital messaging is common practice and digital screens are already in use in areas where patients and the public have conventionally been in attendance, e.g. GP surgeries. Digital screens in community pharmacy for public health messaging could be considered an inevitable progression for public health messaging given concerns about wastage and up-to-date information. The impact, however, on triggering healthier choices and lifestyles requires further investigation.

A "Prime and Expand" strategy using the multifunctional fusion proteins to generate memory-like NK cells for cell therapy.

Adoptive cellular therapy (ACT) using memory-like (ML) natural killer (NK) cells, generated through overnight ex vivo activation with IL-12, IL-15, and IL-18, has shown promise for treating hematologic malignancies. We recently reported that a multifunctional fusion molecule, HCW9201, comprising IL-12, IL-15, and IL-18 domains could replace individual cytokines for priming human ML NK cell programming ("Prime" step). However, this approach does not include ex vivo expansion, thereby limiting the ability to test different doses and schedules. Here, we report the design and generation of a multifunctional fusion molecule, HCW9206, consisting of human IL-7, IL-15, and IL-21 cytokines. We observed > 300-fold expansion for HCW9201-primed human NK cells cultured for 14 days with HCW9206 and HCW9101, an IgG1 antibody, recognizing the scaffold domain of HCW9206 ("Expand" step). This expansion was dependent on both HCW9206 cytokines and interactions of the IgG1 mAb with CD16 receptors on NK cells. The resulting "Prime and Expand" ML NK cells exhibited elevated metabolic capacity, stable epigenetic IFNG promoter demethylation, enhanced antitumor activity in vitro and in vivo, and superior persistence in NSG mice. Thus, the "Prime and Expand" strategy represents a simple feeder cell-free approach to streamline manufacturing of clinical-grade ML NK cells to support multidose and off-the-shelf ACT.

ACR Appropriateness Criteria® Urinary Tract Infection-Child: 2023 Update.

Urinary tract infection (UTI) is a frequent infection in childhood. The diagnosis is usually made by history and physical examination and confirmed by urine analysis. Cystitis is infection or inflammation confined to the bladder, whereas pyelonephritis is infection or inflammation of kidneys. Pyelonephritis can cause renal scarring, which is the most severe long-term sequela of UTI and can lead to accelerated nephrosclerosis, leading to hypertension and chronic renal failure. The role of imaging is to guide treatment by identifying patients who are at high risk to develop recurrent UTIs or renal scarring. This document provides initial imaging guidelines for children presenting with first febrile UTI with appropriate response to medical management, atypical or recurrent febrile UTI, and follow-up imaging for children with established vesicoureteral reflux. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

ACR Appropriateness Criteria® Soft Tissue Vascular Anomalies: Vascular Malformations and Infantile Vascular Tumors (Non-CNS)-Child.

Soft tissue vascular anomalies may be composed of arterial, venous, and/or lymphatic elements, and diagnosed prenatally or later in childhood or adulthood. They are divided into categories of vascular malformations and vascular tumors. Vascular malformations are further divided into low-flow and fast-flow lesions. A low-flow lesion is most common, with a prevalence of 70%. Vascular tumors may behave in a benign, locally aggressive, borderline, or malignant manner. Infantile hemangioma is a vascular tumor that presents in the neonatal period and then regresses. The presence or multiple skin lesions in an infant can signal underlying visceral vascular anomalies, and complex anomalies may be associated with overgrowth syndromes. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

ACR Appropriateness Criteria® Urinary tract infection-child: 2023 update

Urinary tract infection (UTI) is a frequent infection in childhood. The diagnosis is usually made by history and physical examination and confirmed by urine analysis. Cystitis is infection or inflammation confined to the bladder, whereas pyelonephritis is infection or inflammation of kidneys. Pyelonephritis can cause renal scarring, which is the most severe long-term sequela of UTI and can lead to accelerated nephrosclerosis, leading to hypertension and chronic renal failure. The role of imaging is to guide treatment by identifying patients who are at high risk to develop recurrent UTIs or renal scarring. This document provides initial imaging guidelines for children presenting with first febrile UTI with appropriate response to medical management, atypical or recurrent febrile UTI, and follow-up imaging for children with established vesicoureteral reflux. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

Takotsubo cardiomyopathy after solid organ transplantation: a scoping review.

Takotsubo syndrome (TTS) is a stress-induced cardiomyopathy that causes temporary left ventricular wall motion abnormalities and abrupt reversible heart failure. The incidence of perioperative TTS is proportional to the severity of surgical trauma, the duration of the procedure, and the degree of apparent sympathetic activity. A growing number of articles have discussed TTS after a solid organ transplant (SOT), which is one of the circumstances in which physical and emotional stress are at their highest levels. The majority of published cases involved patients who had received an orthotopic liver transplant (OLT). TTS occurred in 0.3-1.7% of liver transplant recipients, but a limited number of cases of TTS in patients who had received kidney, heart, or lung transplants have also been documented. In this study, we analyzed the TTS instances that developed after SOT, highlighting the symptoms and causes as well as the various treatment approaches that were applied. Most TTS cases following OLT and kidney transplant cases occurred in the first week of the surgery. However, the majority of cases occurred years after heart transplantation. Dizziness, dyspnoea, and chest discomfort are the most typical symptoms. Patients may also experience syncope and generalized weakness. In spite of this, the symptoms differ depending on the transplanted organ. Dyspnoea is a common symptom after lung transplants, whereas chest discomfort and dizziness are a common symptom after liver and kidney transplants. Yet, chest pain is not a typical symptom after a heart transplant.

Lung T1 MRI assessments in children with mild cystic fibrosis lung disease.

RATIONALE: Lung T1 MRI is a potential method to assess cystic fibrosis (CF) lung disease that is safe, quick, and widely available, but there are no data in children with mild CF lung disease. OBJECTIVE: Assess the ability of lung T1 MRI to detect abnormalities in children with mild CF lung disease. METHODS: We performed T1 MRI, multiple breath washout (MBW), chest computed tomography (CT), and spirometry in a cohort of 45 children with mild CF lung disease (6-11 years of age). MAIN RESULTS: Despite mean normal ppFEV1 values, the majority of children with CF in this study exhibited mild lung disease evident in lung clearance index (LCI) measured by MBW, chest CT Brody scores, and percent normal lung perfusion (%NLP) measured by T1 MRI. The %NLP correlated with chest CT Brody scores, as did LCI, but %NLP and LCI did not correlate with each other. Analysis of the Brody subscores showed that %NLP and LCI largely correlated with different Brody subscores. CONCLUSIONS: T1 MRI can detect mild CF lung disease in children and correlates with chest CT findings. The %NLP from T1 MRI and LCI correlate with different chest CT Brody subscores, suggesting they provide complementary information about CF lung disease.

Tonsils at Telethon: developing a standardised collection of tonsil photographs for group A streptococcal (GAS) research.

Introduction: Group A streptococcus (GAS) infections, such as pharyngitis and impetigo, can lead to rheumatic fever and rheumatic heart disease (RHD). Australian Aboriginal and Torres Strait Islander populations experience high rates of RHD and GAS skin infection, yet rates of GAS pharyngitis are unclear. Anecdotally, clinical presentations of pharyngitis, including tonsillar hypertrophy and sore throat, are uncommon. This study aimed to develop a standardised set of tonsil photographs and determine tonsil size distribution from an urban paediatric population. Methods: A prospective cohort of children aged 3-15 years were recruited at the public events "Discover Day" and "Telethon Weekend" (October 2017) in Perth, Western Australia, Australia. Tonsil photographs, symptomatology, and GAS rapid antigen detection tests (RADT) were collected. Tonsil size was graded from the photographs using the Brodsky Grading Scale of tonsillar hypertrophy (Brodsky) by two independent clinicians, and inter-rater reliability calculated. Pharyngitis symptoms and GAS RADT were correlated, and immediate results provided. Results: Four hundred and twenty-six healthy children participated in the study over three days. The median age was seven years [interquartile range (IQR) 5.9-9.7 years]. Tonsil photographs were collected for 92% of participants, of which 62% were rated as good-quality photographs and 79% were deemed of adequate quality for assessment by both clinicians. When scored by two independent clinicians, 57% received the same grade. Average Brodsky grades (between clinicians) were 11%, 35%, 28%, 22% and 5% of grades 0,1,2,3 and 4, respectively. There was moderate agreement in grading using photographs, and minimal to weak agreement for signs of infection. Of 394 participants, 8% reported a sore throat. Of 334 GAS RADT performed, <1% were positive. Discussion: We report the first standardised use of paediatric tonsil photographs to assess tonsil size in urban-living Australian children. This provides a proof of concept from an urban-living cohort that could be compared with children in other settings with high risk of GAS pharyngitis or rheumatic fever such as remote-living Australian Indigenous populations.

The Evolution of Commercial Negative Pressure Wound Therapy Systems over the Past Three Decades.

Significance: Since the introduction of the first commercial negative pressure wound therapy (NPWT) system nearly three decades ago, several key technological innovations have led to the wide adoption of the therapy. This is a review of the history and innovation of commercial NPWT systems for adjunctive management of open wounds. Recent Advances: Technical modifications have broadened NPWT options to include innovative dressing interfaces, tubing configurations, power sources, capability of topical wound solution instillation or irrigation, canister versus canister-free configurations, smart technology, and disposable versus larger reusable therapy units. While these options complicate product selection, they have greatly expanded the potential to manage a wide variety of wounds in patients who previously may not have been candidates for NPWT. Critical Issues: Basic yet mandatory requirements of NPWT include delivering an accurate level of negative pressure to the wound bed, maintaining a seal, removing wound surface exudate through the dressing interface, and patient adherence to prescribed therapy. Meeting these requirements is challenging in the face of variable wound types, wound locations, exudate levels, and exudate viscosity. While there are a growing number of marketed NPWT systems, each may have different characteristics and performance. Evaluating the functionality of each system and relevant accessories is complicated, especially as additional manufacturers enter the market. Understanding the key innovations and specific challenges they are intended to solve may aid health care providers in selecting appropriate NPWT technologies for patients. Future Directions: Evolving technology, including artificial intelligence, will likely play a major role in redefining NPWT safety, simplicity, and reliability.

Elevation of Donor-derived Cell-free DNA Before Biopsy-proven Rejection in Kidney Transplant.

BACKGROUND: Standard-of-care biomarkers for renal allograft rejection are lagging indicators, signaling existing organ injury. This precludes early intervention, when immunological cascades leading to rejection are most susceptible. Donor-derived cell-free DNA (dd-cfDNA) shows promise as an early indicator of rejection, allowing earlier and possibly more effective treatment. This analysis was designed to assess this promise using real-world dd-cfDNA testing evidence. METHODS: This retrospective analysis of the prospective, observational ProActive registry study (NCT04091984) assessed dd-cfDNA and serum creatinine levels before biopsy in 424 patients with ≥1 dd-cfDNA test (n = 1013) in the 6 mo before biopsy. RESULTS: Of 4667 enrolled patients, 1631 patients had ≥18 mo of follow-up data, of which 424 had a biopsy and were included in this analysis. Twenty-six biopsies showed antibody-mediated rejection (ABMR), 62 showed T cell-mediated rejection, and 336 showed nonrejection; each from a unique patient. dd-cfDNA fractions were significantly elevated 5 mo before ABMR biopsies, and 2 mo before T cell-mediated rejection biopsies, compared with nonrejection biopsies. In contrast, serum creatinine did not discriminate between rejection and nonrejection in advance, or concurrent with biopsy. Among patients with nonrejection biopsies, estimated glomerular filtration rate was significantly lower in cases with ≥2 increased dd-cfDNA results (≥1%), compared with those with 0 or 1 increased dd-cfDNA result. CONCLUSIONS: These data indicate that dd-cfDNA is an early indicator of biopsy-proven rejection, especially ABMR, suggesting a greater role for dd-cfDNA in surveillance to identify patients at high risk of ongoing or future rejection, thus requiring closer monitoring, biopsy, or other management changes.