Infectious complications in pediatric patients undergoing CD19+CD22+ chimeric antigen receptor T-cell therapy for relapsed/refractory B-lymphoblastic leukemia.

Chimeric antigen receptor T-cell (CAR-T) therapy is effective in the treatment of relapsed/refractory acute B-lymphoblastic leukemia (R/R B-ALL); however, patients who receive CAR-T therapy are predisposed to infections, with considerable detrimental effects on long-term survival rates and the quality of life of patients. This study retrospectively analyzed infectious complications in 79 pediatric patients with R/R B-ALL treated with CAR-T cells at our institution. Overall, 53 patients developed 88 infections. Nine patients experienced nine infections during lymphodepletion chemotherapy, 35 experienced 41 infections during the early phase (days 0-+ 30 after infusion), and 29 experienced 38 infections during the late phase (day + 31-+ 90 after infusion). Pathogens were identified in 31 infections, including 23 bacteria, seven viruses, and one fungus. Four patients were admitted to the intensive care unit for infection and one died. In a univariate analysis, there were ten factors associated with infection, including tumor load, lymphodepleting chemotherapy, neutrophil deficiency and lymphocyte reduction, cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), etc. In a multivariate analysis, CRS ≥ grade 3 was identified as a risk factor for infection (hazard ratio = 2.41, 95% confidence interval: 1.08-5.36, P = 0.031). Therefore, actively reducing the CRS grade may decrease the risk of infection and improve the long-term quality of life of these patients.

Rinoplastia secundaria: infección nasal en el postoperatorio / Secondary rhinoplasty: postoperative nasal infection

La rinoplastia es una de las intervenciones más comunes en cirugía plástica. Se opera aquí una rinoplastia secundaria por vía abierta injertando los alares y la punta con cartílagos auriculares, mientras el tabique cartilaginoso fue usado para los spreader grafts. Se describe aquí una infección posoperatoria de su punta nasal. Al 9no día de su posoperatorio comienza con la punta nasal congestiva y levemente inflamada. Se medica con una crema con antibióticos, pero el día 14 aparece con la punta nasal muy inflamada y con colección. Cuando en el consultorio el cirujano la ve, como cualquier absceso, decide realizarle drenaje con un trocar 18G, 3 miniincisiones en la piel debajo de la punta nasal, de la que drena un líquido amarronado. Luego con el mismo trocar se realiza un lavado dentro de la cavidad con rifampicina solución. Se medica con trimetoprima-sulfametoxazol (Bactrimforte®) 2 comp/día. Al otro día se observa una notable mejoría. Se continuó con lavado diario durante 4 días con el mismo antibiótico evolucionando rápidamente bien. El Bactrim se lo continúa por 20 días. Al mes la punta nasal está muy bien, deshinchada con cicatrices apenas visibles. A los cuatro meses, la punta está muy blanda, las alas nasales y las narinas normales, la punta con buena proyección igual que el dorso con los spreader graft.

Rhinoplasty is one of the most common interventions in plastic surgery. A secondary open rhinoplasty was carried out grafting the allae and the tip of the nose with conchae cartilage, while the septum was used for spreader grafts. We are here describing this post operatory with a tip of the nose infection.In the control, at the 9th postoperative day, the nasal tip began to be congested and at the 14th post op day the patient showed a clear inflammatory collection. In the office, the surgeon decided to evacuate it with three punctureslike little incisions at the inferior part of the skin tip with a trocar 18G. Through them, drained brownish purulent secretion. With the same trocar, rifampicin solution was injected through these little incisions, like washing the subdermal area. It was medicated with trimethoprim-sulfamethoxazole (Bactrim forte®) 2 tablets/day. The following day, there was a clear improvement in the congestion and erythema of the nose. This procedure of washing was repeated for four days. There was a quick evolution of the inflammatory process and 20 more days, there was no sign of the infection. Four months later, the tip of the nose was soft and the result was considered optimal by the patient and doctors.

Granulocyte transfusions in life-threatening infections of children with hemato-oncological diseases.

Granulocytes are the most important cells for host defense during infections. Granulocyte suspension transfusions (GTx) may be given as additional treatment in severely neutropenic patients with life-threatening infections when antimicrobial therapy is inadequate. The aim of this study was to evaluate the effectiveness and safety of GTx for the treatment of children with hemato-oncological disease, febrile neutropenia and serious life-threatening infections. Patients who underwent GTx between July 2020 and September 2022 were evaluated retrospectively. Hematologic and clinical response rates, adverse effects, characteristics of infection episodes and survival data of the patients were analyzed. During the study period, 60 patients received a total of 313 GTx for 81 infection episodes with a median number of GTx/infection episode of 3 (range 1-29). The median neutrophil count per bag was 20.8 (range 7.9-68.3) × 109 and the median neutrophil count per kg body weight was 0.82 (range 0.17-9.2) × 109. Clinical response was 85 %. Clinical response decreased significantly as the duration of neutropenia increased (p = 0.002). Hematologic response was calculated in 198 GTx (GTx given with pre-transfusion neutrophil count ≤ 0.5 × 109/L); hematologic response rate was 34 %. The infection-related mortality was 15 % and overall survival rate was 87 % and 70 % on days 30 and 90, respectively. No serious side effects were observed in any patient. Granulocyte transfusions appear to be safe and effective supportive treatment in neutropenic children with hematologic/oncologic diseases and severe infections.

Treatment of fracture-related infection in Latin America (FRILA). Proposal for a multicentre regional registry.

Postoperative bone infection is a severe complication in the treatment of fractures. The management of this pathology is challenging, but recent advances have been made to achieve standardization that can help diagnosis and decision-making. However, we are unaware of studies validating these models in Latin America. Therefore, this study aims to collect data from patients with fracture-related infections treated in different institutions in Latin America to create a registry that will assist in future clinical decision-making regarding the diagnostic process and the surgical and medical treatment of these patients.

CAR T therapy beyond cancer: the evolution of a living drug.

Engineering a patient's own T cells to selectively target and eliminate tumour cells has cured patients with untreatable haematologic cancers. These results have energized the field to apply chimaeric antigen receptor (CAR) T therapy throughout oncology. However, evidence from clinical and preclinical studies underscores the potential of CAR T therapy beyond oncology in treating autoimmunity, chronic infections, cardiac fibrosis, senescence-associated disease and other conditions. Concurrently, the deployment of new technologies and platforms provides further opportunity for the application of CAR T therapy to noncancerous pathologies. Here we review the rationale behind CAR T therapy, current challenges faced in oncology, a synopsis of preliminary reports in noncancerous diseases, and a discussion of relevant emerging technologies. We examine potential applications for this therapy in a wide range of contexts. Last, we highlight concerns regarding specificity and safety and outline the path forward for CAR T therapy beyond cancer.

Assessing the cost-effectiveness of integrated case management of Neglected Tropical Diseases in Liberia.

BACKGROUND: In 2017, Liberia became one of the first countries in the African region to develop and implement a national strategy for integrated case management of Neglected Tropical Diseases (CM-NTDs), specifically Buruli ulcer, leprosy, lymphatic filariasis morbidities, and yaws. Implementing this plan moves the NTD program from many countries' fragmented (vertical) disease management. This study explores to what extent an integrated approach offers a cost-effective investment for national health systems. METHODS: This study is a mixed-method economic evaluation that explores the cost-effectiveness of the integrated CM-NTDs approach compared to the fragmented (vertical) disease management. Primary data were collected from two integrated intervention counties and two non-intervention counties to determine the relative cost-effectiveness of the integrated program model vs. fragmented (vertical) care. Data was sourced from the NTDs program annual budgets and financial reports for integrated CM-NTDs and Mass Drug Administration (MDA) to determine cost drivers and effectiveness. RESULTS: The total cost incurred by the integrated CM-NTD approach from 2017 to 2019 was US$ 789,856.30, with the highest percentage of costs for program staffing and motivation (41.8%), followed by operating costs (24.8%). In the two counties implementing fragmented (vertical) disease management, approximately US$ 325,000 was spent on the diagnosis of 84 persons and the treatment of twenty-four persons suffering from NTDs. While 2.5 times as much was spent in integrated counties, 9-10 times more patients were diagnosed and treated. CONCLUSIONS: The cost of a patient being diagnosed under the fragmented (vertical) implementation is five times higher than integrated CM-NTDs, and providing treatment is ten times as costly. Findings indicate that the integrated CM-NTDs strategy has achieved its primary objective of improved access to NTD services. The success of implementing an integrated CM-NTDs approach in Liberia, presented in this paper, demonstrates that NTD integration is a cost-minimizing solution.

Current Concepts of Fracture-Related Infection.

Currently, fracture-related infection (FRI) still represents great challenges in front of orthopaedic surgeons, despite great advances that have been achieved regarding its diagnosis and treatment. Although both FRI and prosthetic joint infection (PJI) belong to osteoarticular infections and share similarities, FRI displays unique characteristics. Diagnosis of FRI is sometimes difficult owing to the nonspecific symptoms, and treatment is usually tricky, with a high risk of infection recurrence. In addition, the long disease course is associated with a significantly elevated risk of disability, both physically and psychologically. Moreover, such a disorder still poses heavy economic burdens to the patients, both personally and socially. Therefore, early diagnosis and reasonable treatment are the key issues for increasing the cure rate, decreasing the risks of infection relapse and disability, and improving the life quality and prognosis of the patients. In this review, we summarized the present concepts regarding the definition, epidemiology, diagnosis, and treatment of FRI.

Reframing Optimal Control Problems for Infectious Disease Management in Low-Income Countries.

Optimal control theory can be a useful tool to identify the best strategies for the management of infectious diseases. In most of the applications to disease control with ordinary differential equations, the objective functional to be optimized is formulated in monetary terms as the sum of intervention costs and the cost associated with the burden of disease. We present alternate formulations that express epidemiological outcomes via health metrics and reframe the problem to include features such as budget constraints and epidemiological targets. These alternate formulations are illustrated with a compartmental cholera model. The alternate formulations permit us to better explore the sensitivity of the optimal control solutions to changes in available budget or the desired epidemiological target. We also discuss some limitations of comprehensive cost assessment in epidemiology.

As Superbugs Flourish, Bacteriophage Therapy Recaptures Researchers' Interest.

This Medical News article discusses the resurgence of phage therapy research for antibiotic-resistant infections.

O manejo de infecções nos pacientes em cuidados paliativos em fase final de vida e processo ativo de morte / The management of infections in palliative care patients in the end-of-life and active process of death

Introdução: O cuidado paliativo é uma abordagem que visa melhorar a qualidade de vida de indivíduos, adultos e crianças e seus familiares, que convivem com doenças que ameaçam a vida. As pessoas em cuidados paliativos podem apresentar quadros de infecção devido a imunossupressão, presença de comorbidades, desidratação e ressecamento da pele, diminuição da função dos neutrófilos e da imunidade celular, pelo uso de corticoides, além da caquexia. As infecções podem provocar sintomas como fadiga, dor, desconforto e representam um grande desafio no cuidado. Os indivíduos com esse quadro demandam ações de enfermagem específicas mediante as terapias propostas pela equipe multiprofissional. Objetivo: Analisar como ocorre o manejo de infecções nos pacientes em cuidados paliativos em fase final de vida e processo ativo de morte em dois serviços hospitalares de saúde. Método: Trata-se de um estudo observacional, analítico e retrospectivo, que foi realizado em dois hospitais localizados no município de Ribeirão Preto, estado de São Paulo, que prestam atendimento a indivíduos em cuidados paliativos e seus familiares. Foram incluídos os prontuários de indivíduos em cuidados paliativos em fase final de vida ou processo ativo de morte, de ambos os sexos, com idade superior a 18 anos, que foram diagnosticados com infecção no período de janeiro a dezembro de 2019 em sua última internação antes do óbito. Foram coletadas, dos prontuários, informações referentes às variáveis sociodemográficas, clínicas e as ações implementadas pela equipe de enfermagem. Resultados: A amostra foi constituída por 113 prontuários, nos quais o diagnóstico oncológico foi o mais prevalente. Houve predominância do diagnóstico clínico para infecção, sendo o foco principal o pulmonar, em indivíduos em fase final de vida. A terapia antimicrobiana foi indicada para 97,3% dos casos. A mediana da duração da antibioticoterapia foi de 7 dias para os indivíduos em fase final de vida e de 2 dias para aqueles em processo ativo de morte. Já o tempo decorrido do início da antibioticoterapia até o óbito foi de 9 dias para os indivíduos em fase final de vida e de 2 dias para aqueles em processo ativo de morte. As intervenções de enfermagem mais frequente foram aferição de sinais vitais, cuidados com a pele e mudança de decúbito; e os procedimentos mais frequentes realizados pela enfermagem foram troca de fralda, punção venosa para inserção de cateter e punção venosa para coleta de exames. Conclusão: O manejo da infecção nos pacientes em cuidados paliativos em fase final de vida e processo ativo de morte ocorre por meio de cuidados e procedimentos que geram desconforto físico, entretanto visando o alívio dos sintomas. Além disso, nota-se a alta frequência de prescrição de antibióticos, principalmente pela via endovenosa. Tais achados devem ser documentados, uma vez que nos convida a refletir sobre nossas atitudes práticas e sobre o que significa estar confortável para essas pessoas, possibilitando incorporar esta informação no desenho de intervenções focadas para potencializar a experiência de conforto

Introduction: Palliative care is an approach that improves the quality of life of individuals, adults and children and their families, who live with life-threatening diseases. People in palliative care may present with infection due to immunosuppression, presence of comorbidities, dehydration and dryness of the skin, decrease in neutrophil function and cellular immunity, due to the use of corticosteroids, in addition to cachexia. Infections can cause symptoms such as fatigue, pain, discomfort and represent a major challenge in care. Individuals with this condition demand specific nursing actions through the therapies proposed by the multidisciplinary team. Objective: To analyze how infections are managed in palliative care patients in the final stage of life and in the active process of death in two hospital health services. Method: This is an observational, analytical and retrospective study, which was carried out in two hospitals located in the city of Ribeirão Preto, state of São Paulo, which provide care to individuals in palliative care and their families. The medical records of individuals in palliative care in the final stage of life or in the active process of death, of both sexes, aged over 18 years, who were diagnosed with infection in the period from January to December 2019 in their last hospitalization before death. Information regarding sociodemographic and clinical variables and the actions implemented by the nursing team were collected from the medical records. Results: The sample consisted of 113 medical records, in which the oncological diagnosis was the most prevalent. There was a predominance of the clinical diagnosis for infection, the main focus being the pulmonary, in individuals in the final stage of life. Antimicrobial therapy was indicated for 97.3% of cases. The median duration of antibiotic therapy was 7 days for individuals in the final stage of life and 2 days for those in the active process of dying. The time elapsed from the beginning of antibiotic therapy to death was 9 days for individuals in the final stage of life and 2 days for those in the active process of death. The most frequent nursing interventions were measuring vital signs, skin care and changing positions; and the most frequent procedures performed by nursing were diaper changes, venipuncture for catheter insertion and venipuncture for collection of exams. Conclusion: The management of infection in palliative care patients in the final stage of life and in the active process of death occurs through care and procedures that generate physical discomfort, however aiming at relieving symptoms. In addition, there is a high frequency of prescription of antibiotics, mainly by the intravenous route. Such findings must be documented, as they invite us to reflect on our practical attitudes and on what it means to be comfortable for these people, making it possible to incorporate this information into the design of interventions focused on enhancing the experience of comfort

The PRINCIPAL Network: A Model to Optimize Infection Care and Prevention in Pediatric Oncology in the Latin American Region.

PURPOSE: Children with cancer are at high risk for poor outcomes, and health care providers are often unfamiliar with best practices in infection care and prevention (IC&P) in this small and fragile population. Graduates of training courses in IC&P in immunocompromised hosts identified a need for a community that would enable members to share health care experiences, provide resources for continuing medical education, and foster collaborative research and quality improvement opportunities. We developed a Latin American network, Prevencionistas e Infectólogos para Cáncer Pediátrico en América Latina, to grow and sustain the expertise of the clinical workforce in IC&P. Here, we describe the network, how we built it, and its early outcomes. METHODS: We began by codesigning the mission, vision, objectives, and values. We then established the structure for leadership and network management to provide a functional uniformity and sustainability. Virtual meetings with network members and strategic in-person gatherings optimized the use of the time and resources of the network. RESULTS: The network has seen good participation by members and candidates for membership, who have provided feedback on case-based learning. Members have attended training sessions on quality improvement, research in human subjects, and IC&P in pediatric oncology at national and regional meetings and workshops. Network members have presented their work at regional and global meetings, and publications are beginning to emerge from this community. A direct effect of the Prevencionistas e Infectólogos para Cáncer Pediátrico en América Latina network has been the creation of a similar network for the Asia Pacific region, and a third network is being planned. CONCLUSION: We have demonstrated the power of a discipline-specific network structure to facilitate sharing of evidence-based information that enhances the quality-of-care delivery in pediatric oncology.

Remembrance of infections past.

Host-derived metabolite trains the microbiota to develop colonization resistance.

Immunometabolism in biofilm infection: lessons from cancer.

BACKGROUND: Biofilm is a community of bacteria embedded in an extracellular matrix, which can colonize different human cells and tissues and subvert the host immune reactions by preventing immune detection and polarizing the immune reactions towards an anti-inflammatory state, promoting the persistence of biofilm-embedded bacteria in the host. MAIN BODY OF THE MANUSCRIPT: It is now well established that the function of immune cells is ultimately mediated by cellular metabolism. The immune cells are stimulated to regulate their immune functions upon sensing danger signals. Recent studies have determined that immune cells often display distinct metabolic alterations that impair their immune responses when triggered. Such metabolic reprogramming and its physiological implications are well established in cancer situations. In bacterial infections, immuno-metabolic evaluations have primarily focused on macrophages and neutrophils in the planktonic growth mode. CONCLUSION: Based on differences in inflammatory reactions of macrophages and neutrophils in planktonic- versus biofilm-associated bacterial infections, studies must also consider the metabolic functions of immune cells against biofilm infections. The profound characterization of the metabolic and immune cell reactions could offer exciting novel targets for antibiofilm therapy.

The rationale for including osteopathic manipulative treatment in the management of infections: a hermeneutic review.

INTRODUCTION: As the prevalence of drug-resistant infections continues to outpace the development of new antibiotics, we must explore all reasonable options for enhancing the effectiveness of existing anti-infectives. The emergence of novel pathogens without initial drug treatments or vaccines, typified by the severe acute respiratory syndrome coronavirus-2 pandemic, further underscores the need for non-pharmacologic adjunctive measures for infection management. Osteopathic manipulative treatment (OMT) may represent such an adjunct. AREAS COVERED: PubMed, CINAHL, Google Scholar, Cochrane databases and relevant chapters of major osteopathic texts were searched for animal experiments, case reports, observational studies, non-randomized, and randomized trials pertaining to infection, OMT, and the complications or safety of OMT. OMT was associated with one or more of the following: decreased bacterial colony counts in lung tissue; changes in immunologic profiles manifested by significant differences dendritic cells and levels of IL-8, MCP-1, MIP-1a, and G-CSF; shorter durations of IV antibiotics; decreased length of hospitalization; decreased rates of respiratory failure and death; decreased post-surgical lengths of stay; and enhanced patient satisfaction. EXPERT OPINION: Preliminary, lower-grade evidence suggests that OMT can improve some infection-related outcomes, and is safe. The role of OMT in infection management should undergo further controlled trials without delay.

The immune landscape in BCR-ABL negative myeloproliferative neoplasms: inflammation, infections and opportunities for immunotherapy.

Breakpoint cluster region-Abelson (BCR-ABL) negative myeloproliferative neoplasms (MPNs) are chronic myeloid neoplasms initiated by the acquisition of gene mutation(s) in a haematopoietic stem cell, leading to clonal expansion and over-production of blood cells and their progenitors. MPNs encompass a spectrum of disorders with overlapping but distinct molecular, laboratory and clinical features. This includes polycythaemia vera, essential thrombocythaemia and myelofibrosis. Dysregulation of the immune system is key to the pathology of MPNs, supporting clonal evolution, mediating symptoms and resulting in varying degrees of immunocompromise. Targeting immune dysfunction is an important treatment strategy. In the present review, we focus on the immune landscape in patients with MPNs - the role of inflammation in disease pathogenesis, susceptibility to infection and emerging strategies for therapeutic immune modulation. Further detailed work is required to delineate immune perturbation more precisely in MPNs to determine how and why vulnerability to infection differs between clinical subtypes and to better understand how inflammation results in a competitive advantage for the MPN clone. These studies may help shed light on new designs for disease-modifying therapies.

Characteristics and recognition of early infections in patients treated with commercial anti-CD19 CAR-T cells.

The characteristics of infections following chimeric antigen receptor T (CAR-T) cells targeting CD19 in real-word population are obscure. We analyzed infections' characteristics in the first month among consecutive patients with diffuse large B-cell lymphoma (DLBCL) (n = 60, median age, 69.3 years), treated with commercial CAR-T cells. ECOG performance status (PS) was 2-3 in most patients (58%). Infections were observed in 45% of patients (16, 27%, bacterial infections, and 14, 23%, viral infections). Bacterial infection included clinically documented infection in 7 (Pneumonia, n = 5; periodontal infection, n = 1; and cellulitis, n = 1) and microbiology documented infection (MDI) in 9 patients (Gram-negative rod, n = 5; Gram-positive cocci, n = 3, bacteremia; polymicrobial, n = 1). The most common viral infection was cytomegalovirus (CMV) reactivation (n = 10, 17%) leading to initiation of anti-CMV treatment in 6 (60%) among these patients. None had CMV disease. In univariate analysis, immune effector cell-associated neurotoxicity syndrome (ICANS) was associated with higher incidence of bacterial infection (OR=4.5, P = .018), while there was a trend for lower incidence of bacterial infections in patients with chemosensitive disease to bridging therapy (OR=0.375, P = .074). Age or PS was not associated with increased risk of bacterial infection. Increase in C-reactive protein (CRP) prior to fever onset was associated with microbiologically documented infections. We conclude that infections are common in the first month following CAR-T-cell administration, however, were not increased in elderly patients or those presenting with poorer PS. Increase in CRP prior to fever onset could support infection over cytokine release syndrome.