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.

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.

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.

Antimicrobial blue light: A 'Magic Bullet' for the 21st century and beyond?

Over the past decade, antimicrobial blue light (aBL) at 400 - 470 nm wavelength has demonstrated immense promise as an alternative approach for the treatment of multidrug-resistant infections. Since our last review was published in 2017, there have been numerous studies that have investigated aBL in terms of its, efficacy, safety, mechanism, and propensity for resistance development. In addition, researchers have looked at combinatorial approaches that exploit aBL and other traditional and non-traditional therapeutics. To that end, this review aims to update the findings from numerous studies that capitalize on the antimicrobial effects of aBL, with a focus on: efficacy of aBL against different microbes, identifying endogenous chromophores and targets of aBL, Resistance development to aBL, Safety of aBL against host cells, and Synergism of aBL with other agents. We will also discuss our perspective on the future of aBL.

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.

Hyperbaric Oxygen Therapy: An Effective Auxiliary Treatment Method for Large Jaw Cysts.

Background: To evaluate hyperbaric oxygen therapy (HBOT) on infection rates and repair rates during the treatment of large jaw cysts. Methods: A prospective randomized, non-blinded, controlled clinical trial included 90 patients with jaw cysts, randomly divided into three groups. Patients were treated with enucleations and bone substitute was used in the experimental and control groups. The experimental group received HBOT. The primary predictor variable was HBOT. The infection rate, repair rate, preoperative volume of the jaw cysts, age, and sex were statistically analyzed. The Fisher exact test was used to compare the infection rate and postoperative complications. The repair rate of the bone defects was analyzed using the repeated-measures analysis of variance and the least significant difference tests. The Kendall's coefficient of concordance and Kappa statistics were calculated to evaluate the consistency between the two investigators. Results: The infection rate was 3.4% in the experimental group, 14.3% in the blank group, and 32.1% in the control group (P<0.05). The repair rate in the experimental group was significantly higher than in the control and blank groups at 1, 3 and 6 months after surgery (P<0.05). Conclusion: The results showed that HBOT reduced the postoperative infection rate following the enucleation of large jaw cysts with bone substitute filling, and it also improved the bone repair rate.

Mesenchymal Stem Cells: Potential Therapeutic Prospect of Paracrine Pathways in Neonatal Infection.

Infection is the leading cause of admission and mortality in neonatal intensive care units. Immature immune function and antibiotic resistance make the treatment more difficult. However, there is no effective prevention for it. Recently, more and more researches are focusing on stem cell therapy, especially mesenchymal stem cells (MSCs); their potential paracrine effect confer MSCs with a major advantage to treat the immune and inflammatory disorders associated with neonatal infection. In this review, we summarize the basal properties and preclinical evidence of MSCs and explore the potential mechanisms of paracrine factors of MSCs for neonatal infection.