Metabolic adaptations in severe obesity: Insights from circulating oxylipins before and after weight loss.

BACKGROUND: The relationship between lipid mediators and severe obesity remains unclear. Our study investigates the impact of severe obesity on plasma concentrations of oxylipins and fatty acids and explores the consequences of weight loss. METHODS: In the clinical trial identifier NCT05554224 study, 116 patients with severe obesity and 63 overweight/obese healthy controls matched for age and sex (≈2:1) provided plasma. To assess the effect of surgically induced weight loss, we requested paired plasma samples from 44 patients undergoing laparoscopic sleeve gastrectomy one year after the procedure. Oxylipins were measured using ultra-high-pressure liquid chromatography coupled to a triple quadrupole mass spectrometer via semi-targeted lipidomics. Cytokines and markers of interorgan crosstalk were measured using enzyme-linked immunosorbent assays. RESULTS: We observed significantly elevated levels of circulating fatty acids and oxylipins in patients with severe obesity compared to their metabolically healthier overweight/obese counterparts. Our findings indicated that sex and liver disease were not confounding factors, but we observed weak correlations in plasma with circulating adipokines, suggesting the influence of adipose tissue. Importantly, while weight loss restored the balance in circulating fatty acids, it did not fully normalize the oxylipin profile. Before surgery, oxylipins derived from lipoxygenase activity, such as 12-HETE, 11-HDoHE, 14-HDoHE, and 12-HEPE, were predominant. However, one year following laparoscopic sleeve gastrectomy, we observed a complex shift in the oxylipin profile, favoring species from the cyclooxygenase pathway, particularly proinflammatory prostanoids like TXB2, PGE2, PGD2, and 12-HHTrE. This transformation appears to be linked to a reduction in adiposity, underscoring the role of lipid turnover in the development of metabolic disorders associated with severe obesity. CONCLUSIONS: Despite the reduction in fatty acid levels associated with weight loss, the oxylipin profile shifts towards a predominance of more proinflammatory species. These observations underscore the significance of seeking mechanistic approaches to address severe obesity and emphasize the importance of closely monitoring the metabolic adaptations after weight loss.

Serum Arylesterase, Paraoxonase, and Lactonase Activities and Paraoxonase-1 Concentrations in Morbidly Obese Patients and Their Relationship with Non-Alcoholic Steatohepatitis.

Paraoxonase-1 (PON1) is an antioxidant enzyme associated with high-density lipoproteins (HDL). Reduced serum PON1 activity is found in diseases marked by oxidative stress and inflammation, but its role in obesity remains unclear. This study investigated PON1 activities and concentrations in morbidly obese individuals and explored the impacts of the genetic polymorphism PON1 rs662 and non-alcoholic fatty liver disease on enzymatic properties. We recruited 1349 morbidly obese patients undergoing bariatric surgery and 823 non-obese volunteers. PON1-related variables, including arylesterase, paraoxonase, and lactonase activities and PON1 concentrations, were examined. Our results showed that morbidly obese individuals exhibited higher PON1 concentrations but lower enzymatic activities than non-obese individuals. We observed inverse associations of arylesterase and paraoxonase activities with waist circumference (rho = -0.24, p < 0.001, and rho = -0.30, p < 0.001, respectively) and body mass index (rho = -0.15, p = 0.001, and rho = -0.23, p < 0.001), as well as direct associations of arylesterase, paraoxonase, and lactonase activities with HDL cholesterol (rho = 0.11, p = 0.005, rho = 0.20, p < 0.001, and rho = 0.20, p < 0.001). No significant differences were observed regarding metabolic syndrome, type 2 diabetes mellitus, hypertension, dyslipidemia, rs662 polymorphism allele frequencies, or the diagnosis of non-alcoholic steatohepatitis. Nevertheless, correlations were found between certain PON1-related variables, steatosis, and ballooning. In conclusion, changes in PON1-related variables in morbidly obese patients are dependent on the disease itself and HDL levels. The relationships between these variables and specific liver histological changes raise intriguing questions for consideration in future studies.

At-Home Foscarnet Administration in Patients with Cytomegalovirus Infection Post-Allogeneic Stem Cell Transplantation: A Unicentric, Safe, and Feasible Program.

Cytomegalovirus (CMV) infection is a relevant cause of morbimortality in patients receiving allogeneic stem cell transplantation (allo-HCT). Foscarnet (FCN) is an effective drug against CMV administered intravenously and usually on an inpatient basis. The Home Care Unit (HCU) for hematologic patients at our hospital designed an at-home FCN administration model to avoid the hospitalization of patients requiring FCN treatment. This study analyzes whether the at-home administration of FCN is as safe and effective as its hospital administration. We collected and compared demographic, clinical, analytical, and economic data of patients with CMV infection post-allo-HCT who received FCN in the hospital (n = 16, 17 episodes) vs. at-home (n = 67, 88 episodes). The proportions of patients with cured CMV infections were comparable between the two groups (65.9% vs. 76.5%, p = 0.395). The median duration of FCN treatment was 15 (interquartile range [IQR] 9-23) and 14 (IQR 11-19) days in the HCU and inpatient cohorts, respectively (p = 0.692). There were no significant differences in the FCN toxicities between groups except for hypocalcemia (26.1% vs. 58.8%, p = 0.007), which was more prevalent in the inpatient cohort. A significant cost-effectiveness was found in the HCU cohort, with a median savings per episode of EUR 5270. It may be concluded that home administration of FCN is a safe, effective, and cost-efficient therapeutic option for patients with CMV infection and disease.

Diseño y evaluación computacional de LYTACS para la degradación selectiva de MMP-2 / Computational design and evaluation of LYTACS for the selective degradation of MMP-2

Los LYTACs (LYsosome TArgeting Chimeras) son una novedosa estrategia farmacológica basada en la degradación dirigida de proteínas extracelulares y transmembrana. Su mecanismo de acción se basa en la utilización de un receptor de membrana para internalizar a una proteína diana y promover su degradación lisosomal. Hasta la fecha, su desarrollo se ha basado en el uso de anticuerpos para la unión a la proteína diana, lo cual presenta ciertas desventajas desde el punto de vista farmacocinético y sintético. El objetivo de este trabajo es diseñar un LYTAC capaz de inducir la degradación selectiva de MMP-2 (LYTAC-MMP2), una metaloproteasa de la matriz que se encuentra sobreexpresada en diversos tipos de cáncer. LYTAC-MMP2 está formado por un ligando del receptor de manosa-6-fosfato independiente de cationes (CI- MPR) y un inhibidor selectivo de MMP2 previamente descrito. Se han empleado métodos computacionales de modelado por homología, docking y dinámica molecular para estudiar el receptor CI-MPR y su mecanismo de internalización, así como para la comparación del comportamiento dinámico libre en agua de un ligando de CI-MPR descrito en la bibliografía y el LYTAC-MMP2.(AU)

LYTACs (LYsosome TArgeting Chimeras) are a novel pharmacological strategy based on the targeted protein degradation of extracellular and transmembrane proteins. Their mechanism of action is based on the use of a membrane receptor to internalize a target protein and mediate its lysosomal degradation. To date, its development has been focused on the use of antibodies for target binding, which has certain disadvantages from the pharmacokinetic and synthetic point of view. The aim of this work is to design a LYTAC capable of inducing the selective degradation of MMP-2 (LYTAC-MMP2), a matrix metalloprotease that is overexpressed in many types of cancer. LYTAC-MMP2 consists of a cation-independent mannose-6-phosphate receptor (CI-MPR) ligand and a selective MMP-2 inhibitor developed by our research group. Computational methods of homology modelling, docking and molecular dynamics have been used to study the CI-MPR receptor and its internalization mechanism, as well as for the comparison of the dynamic behaviour in water of a CI-MPR ligand described in the literature and LYTAC-MMP2.(AU)

Cycad phylogeny predicts host plant use of Eumaeus butterflies.

Eumaeus butterflies are obligate herbivores of Zamia, the most diverse neotropical genus of cycads. Eumaeus-Zamia interactions have been characterized mainly for species distributed in North and Central America. However, larval host plant use by the southern Eumaeus clade remains largely unknown, precluding a comprehensive study of co-evolution between the genera. Here, we combine fieldwork with museum and literature surveys to expand herbivory records for Eumaeus from 21 to 38 Zamia species. We inferred a time-calibrated phylogeny of Eumaeus to test for distinct macroevolutionary scenarios of larval host plant conservatism and co-evolution. We found a remarkable coincidence between Eumaeus and Zamia diversification, with the butterfly stem group diverging at the same time as the most recent radiation of Zamia in the Miocene. Cophylogenetic reconciliation analyses show a strong cophylogenetic signal between cycads and their butterfly herbivores. Bipartite model-based approaches indicate that this is because closely related Zamia species are used by the same Eumaeus species, suggesting larval host plant resource tracking by the butterfly herbivores. Our results highlight a case of tight evolution between Eumaeus butterflies and cycads, pointing to the generality of correlated evolution and phylogenetic tracking in plant-herbivore interactions across seed plants.

Solubility of Amino Acids in the Eutectic Solvent Constituted by Sodium Acetate Trihydrate and Urea and in Its Mixture with Water.

Industrial fish and aquaculture processing leads to the generation of a huge quantity of by-products, whose accumulation and mismanagement involve serious environmental consequences as well as high economic losses. Taking advantage of these residues as a source of added-value compounds must be a priority in a circular economy. This work is a preliminary study to analyze the possibility of using the eutectic mixture of urea and sodium acetate trihydrate as a solvent for collagen extraction. To that end, the solid-liquid equilibrium of the system was determined in order to define the exact composition and temperature of the eutectic. The solubility in this solvent of the main amino acids that constitute fish collagen was studied at several temperatures and atmospheric pressure. At 308.15 K, solubilities of the major constituents of the target protein, namely L-proline, trans-4-hydroxy-L-proline, and glycine, were 0.19, 0.16, and 0.12 (mass fraction), respectively. These values increased with temperature. Dilution with water (50 wt%) allowed operation at lower temperature and led to an increase in the solubilities. The van 't Hoff model was satisfactorily used to correlate the experimental data and to calculate apparent properties of dissolution. All the dissolution processes studied herein are endothermic, non-spontaneous, and enthalpy-driven. Both the eutectic and its mixture with water are promising solvents for the design of an environmentally benign process for collagen extraction.

Retinal Nerve Fiber Layer Analysis in Children With Migraine With and Without Aura Using Optical Coherence Tomography: A Case-Control Study.

PURPOSE: To evaluate retinal nerve fiber layer (RNFL) thickness in children with migraine, with and without aura, compared to healthy controls using optical coherence tomography (OCT). METHODS: In this cross-sectional case-control study, patients with a diagnosis of migraine with aura (MwA) or without aura (MwoA) were considered and healthy children were included as controls. Age, sex, duration of migraine, number of episodes per month, duration of episodes, and use of prophylactic treatment with magnesium were recorded. All patients underwent complete ophthalmologic, neurologic, and pediatric examination. Optic nerve OCT images were obtained using Heidelberg Spectralis OCT (Heidelberg Engineering) and mean global RNFL thickness and the average thickness for each sector were noted. RESULTS: Thirty-seven children were included: 17 with migraine (9 MwoA and 8 MwA) and 20 controls, the mean age being 13.8 ± 2.9 (range: 8 to 16) and 13.4 ± 2.5 (range: 7 to 16) years, respectively. No significant differences in RNFL thickness were found when comparing all patients who had migraine with healthy controls. However, children with MwA showed statistically significant reductions in RNFL thickness in the temporal (mean difference: 7.83; 95% CI: 0.52 to 15.14, P = .027) and inferior-temporal (mean difference: 16.06; 95% CI: 1.95 to 30.16, P = .027) sectors compared to patients with MwoA. None of the other sectors showed statistically significant differences between groups (all P > .05). In the migraine group, negative correlations were detected between the number of episodes per month and RNFL thickness in the nasal-superior quadrant (r = -.420; P = .021). CONCLUSIONS: Children with MwA may present a decrease in RNFL thickness, which is associated with the number of episodes per month. [J Pediatr Ophthalmol Strabismus. 2023;60(3):196-202.].

Efficacy and safety of the PreserFlo implant with mitomycin C in childhood glaucoma after previous failed glaucoma surgeries.

PURPOSE: This study aims to evaluate the efficacy and safety of the PreserFlo MicroShunt (Santen, Osaka, Japan) in lowering intraocular pressure (IOP) in childhood glaucoma patients with previous failed glaucoma surgeries. METHODS: This is a prospective case review of consecutive PreserFlo procedures performed in childhood glaucoma patients after failed surgeries. Age, sex, diagnosis, and previous glaucoma surgeries, as well as visual acuity, IOP, and treatment in the preoperative visit and all follow-up visits were collected. Outcome measures included IOP reduction from baseline, mean IOP change from baseline at month 6, medication use at 6 months, complications, adverse events, and need for further procedures. RESULTS: Fourteen patients were included, 8 (57%) males and 6 (43%) females; the mean age was 27.5 ± 13.5 years. Nine patients (64%) had at least two trabeculectomies, and 6 patients (43%) had at least one trabeculectomy and a glaucoma drainage implant. The mean IOP change from baseline was 11.3 ± 4.9 mmHg at 12 months. At 12 months, 12 patients (86%) presented ≥ 20% IOP lowering from baseline, and 11 patients (79%) presented ≥ 30%. The mean medication count decreased from 3.9 ± 0.7 (baseline) to 0.7 ± 1.3 (12 months). No intraoperative complications were reported. No adverse events were noted. No secondary filtration surgery was required, although bleb needling was required in one case, 1 month after the surgery. CONCLUSIONS: PreserFlo with MMC can be used successfully to treat uncontrolled IOP in childhood glaucoma cases with previous failed surgeries. Larger studies with longer follow-up are needed to further explore the role of the device in resistant childhood glaucoma cases.

Abducens and Trochlear Nerve Palsies After COVID-19 Vaccination: Report of Two Cases.

The authors report two cases of an abducens palsy and a trochlear nerve palsy, respectively, in two patients who received a coronavirus disease 2019 (COVID-19) vaccine 2 weeks previously. Given the lack of other symptoms, normal test results, and spontaneous resolution of the diplopia, a likely association with the COVID-19 vaccine was suggested. [J Pediatr Ophthalmol Strabismus. 2022;59(5):e50-e53.].

Midterm results of a new personalized knee implant for total knee arthroplasty: implant survivorship and patient-reported outcome after five years' follow-up.

PURPOSE: The Persona® system is a newly launched implant designed for total knee arthroplasty (TKA) with technical innovations intended for a better functional outcome and higher flexion range. The aim of this study is to evaluate midterm outcomes and survivorship of a cohort of patients with a minimum of 5-year follow-up and to confirm previous results described in the literature. METHODS: A cohort of 91 knees (85 patients) that underwent a patella-preserving TKA with the Persona® implant and who were followed for a mean of 5.9 years' period was included in the study. Functional values were measured: Oxford Knee Score (OKS), Knee Society Knee score (KSKS) and Knee Society Function score (KSFS). Range of movement (ROM), lower limb axis correction, mobilization and complications were also registered at the last follow-up and underwent statistical analysis. RESULTS: We found a low rate of complications or radiological changes with an implant-related revision rate of 2.19%. Mean results for PROMS were 44.21 ± 4 in OKS, 90.94 ± 2.4 in KSS and 97.88 ± 9.6 in KSFS. Mean postoperative ROM was 120.8º ± 12.37º. There was no change in implant positions at the final follow-up. We found radiolucent lines in 3 knees (3.29%). CONCLUSION: At a mean follow-up of 5.9 years, the implant-related cumulative percentage revision rate was 3.3% (2 of 91) at a mean follow-up of 5.9 years, with good clinical and functional results.

Banana Pseudo-Stem Increases the Water-Holding Capacity of Minced Pork Batter and the Oxidative Stability of Pork Patties.

Banana pseudo-stem (BPS), which is rich in fibre and polyphenols, is a potential functional ingredient for the food industry. In this study, BPS was added at concentrations of 1.5, 3.0, and 4.5 g/kg to a minced pork batter to evaluate its performance as a filler and to pork burger patties to evaluate its performance as a natural antioxidant. The effects of BPS were compared with those of carrageenan and ascorbate, which are a conventional binder and antioxidant, respectively. The performance of BPS was similar to that of carrageenan in terms of the cooking yield and texture of the cooked batter. BPS reduced the brightness of fresh patties and appeared to reduce oxidative discolouration during the frozen storage of raw patties. Moreover, BPS reduced the levels of thiobarbituric acid reactive substances (TBARS) during the refrigerated and frozen storage of cooked patties. A greater decrease in TBARS formation was observed with 4.5 g BPS/kg compared with 0.5 g sodium ascorbate/kg during refrigerated storage. In contrast to ascorbate, BPS promoted the presence of lipid-derived volatile compounds induced by thermal breakdown in the headspace of cooked patties. Nonetheless, this effect was reduced as the amount of BPS in the patties increased. In cooked minced meat products, BPS could increase cooking yields and lipid oxidative stability during storage and might result in a more intense flavour.

Hospital and outpatient models for Hematopoietic Stem Cell Transplantation: A systematic review of comparative studies for health outcomes, experience of care and costs.

The number of Hematopoietic Stem Cell Transplantations has risen in the past 20 years. The practice of outpatient Hematopoietic Stem Cell Transplantation programs is increasing in an attempt to improve the quality of patient care and reduce the demand for hospital admission. A systematic review of 29 comparative studies between in-hospital and outpatient treatment of Hematopoietic Stem Cell Transplantation, with no restriction by outpatient regime was conducted. This study aims to analyse the current evidence on the effects of the outpatient model on patient-centred outcomes, comparing both in-hospital and outpatient models for autologous and allogeneic HSCT using the Triple Aim framework: health outcomes, costs and experience of care. We found evidence on improved health outcomes and quality of life, on enhanced safety and effectiveness and on reduced overall costs and hospital stays, with similar results on overall survival rates comparing both models for autologous and allogeneic patients. We also found that the outpatient Hematopoietic Stem Cell Transplantation is a safe practice as well as less costly, it requires fewer days of hospital stay both for autologous and allogeneic transplantations. Under a situation of an increasing number of transplants, rising healthcare costs and shortages of hospital capacity, incorporating outpatient models could improve the quality of care for people requiring Hematopoietic Stem Cell Transplantation programs.

Long-Term Outcomes of 496 Anatomical Cementless Modular Femoral Stems: Eleven to Twenty Years of Follow-Up.

BACKGROUND: The aim of the study is to assess the long-term outcomes of this specific stem (anatomical cementless modular stem ESOP), to review the survivorship, complication rate, and radiographic and clinical outcomes. METHODS: Descriptive and analytical retrospective longitudinal observational study of patients was operated on total hip arthroplasty between 1998 and 2007. Four hundred ninety-six prostheses corresponding to 447 patients were reviewed, mean age was 65.8 years (standard deviation [SD] ±11.6 years), and median follow-up time was 13.4 years (range 1-20). The most used cups were cementless (75.8%). The most frequent friction pairs were metal-polyethylene (53.1%) and ceramic-polyethylene (24.2%). Main variables analyzed were stem survival, subsidence, coronal orientation, osteolysis, reintervention, and Oxford Hip Score. RESULTS: From 496 implants, there were 22 lost to follow-up (4.4%). Stem revision was performed in 51 patients: 26 periprosthetic joint infections (2-stage revision), 16 periprosthetic fractures, and 8 one-stage revisions (6 real aseptic loosening with negative culture after revision). The stem survivorship at more than 15 years for any reason was 89.2% and for aseptic loosening 97.97%. No specific complications were found due to modularity. The mean subsidence and orientation was 2.06 mm (SD ±5.11 mm) and 0.41° varus (SD ±2.20°) respectively. Subsidence >5 mm or varus >5° was associated with a higher revision rate. Osteolysis was found in 110 patients (zone I = 79, VII = 57), associated with zirconium-polyethylene, without relationship to the stem revision rate or Oxford Hip Score. CONCLUSION: To our knowledge, this study represents the largest series of this stem, revealing an excellent survival rate and long-term clinical outcomes similar to the best results of classical cementless stems published in the literature.

Physical Properties of Flours Obtained from Wasted Bread Crusts and Crumbs.

One third of the food produced in the world is wasted. Bread is one of the most wasted foods both during the distribution process and in households. To use these breads, it is necessary to get to know the properties of the flours that can be obtained from them. The purpose of this work is to know how the type of bread and its zone (crumb or crust) influence the characteristics of the flours obtained from the wasted bread. For this, flours made from the crumbs and crusts of eight different breads have been analysed. Their hydration properties, cold and post-heating rheology and gelling properties as well as the colour of flours and gels have been studied. Bread flours present higher water-holding capacity (WHC) and water-binding capacity (WBC) values and higher elastic modulus (G') and viscous modulus (G") values, both in cold conditions and after heating, than wheat flours. However, they generate weaker gels. Crust flours, and the gels obtained from them, are darker than those from crumbs and their gels. In terms of hydration and rheology, pan and wholemeal bread flours are generally lower than other bread flours. These flours also generate softer gels, possibly caused by the dilution of starch with other components. It can be concluded that the properties shown by wasted bread flours allow them to be reintroduced in the food chain as an ingredient in different products.

Granular Cell Tumor of the Hand: Unusual Malignancy of a Previous Benign Lesion: A Case Report.

CASE: Malignant granular cell tumors are uncommon soft-tissue tumors. We describe a granular cell tumor that presented as a benign hand nodule diagnosed by biopsy and image. The patient refused local excision. After 15 years, the patient came back because of symptomatic growth, and a malignant granular cell tumor was diagnosed, with metastatic disease. Despite surgical disarticulation and adjuvant treatment, she died after 8 months. The pathological examination revealed the tumor had progressed to malignant behavior. CONCLUSIONS: Our findings highlight the importance of a closer follow-up. Although unusual, we must be aware of the possibility of a change of behavior from benign to malignant granular cell tumor.

The avoidance of G-CSF and the addition of prophylactic corticosteroids after autologous stem cell transplantation for multiple myeloma patients appeal for the at-home setting to reduce readmission for neutropenic fever.

BACKGROUND: Autologous stem cell transplantation (ASCT) remains the standard of care for young multiple myeloma (MM) patients; indeed, at-home ASCT has been positioned as an appropriate therapeutic strategy. However, despite the use of prophylactic antibiotics, neutropenic fever (NF) and hospital readmissions continue to pose as the most important limitations in the outpatient setting. It is possible that the febrile episodes may have a non-infectious etiology, and engraftment syndrome could play a more significant role. The aim of this study was to analyze the impact of both G-CSF withdrawal and the addition of primary prophylaxis with corticosteroids after ASCT. METHODS: Between January 2002 and August 2018, 111 MM patients conditioned with melphalan were managed at-home beginning +1 day after ASCT. Three groups were established: Group A (n = 33) received standard G-CSF post-ASCT; group B (n = 32) avoided G-CSF post-ASCT; group C (n = 46) avoided G-CSF yet added corticosteroid prophylaxis post-ASCT. RESULTS: The incidence of NF among the groups was reduced (64%, 44%, and 24%; P<0.001), with a non-significant decrease in hospital readmissions as well (12%, 6%, and 2%; P = 0.07). The most important variables identified for NF were: HCT-CI >2 (OR 6.1; P = 0.002) and G-CSF avoidance plus corticosteroids (OR 0.1; P<0.001); and for hospital readmission: age ≥60 years (OR 14.6; P = 0.04) and G-CSF avoidance plus corticosteroids (OR 0.07; P = 0.05). CONCLUSIONS: G-CSF avoidance and corticosteroid prophylaxis post ASCT minimize the incidence of NF in MM patients undergoing at-home ASCT. This approach should be explored in a prospective randomized clinical trial.

Mycobacterium lentiflavum. Infección pulmonar en una paciente inmunocompetente / Mycobacterium lentiflavum. Pulmonary infection in an immunocompetent patient

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Impact of intensifying primary antibiotic prophylaxis in at-home autologous stem cell transplantation program for lymphoma patients.

Despite the use of fluoroquinolone (FQ) prophylaxis, neutropenic fever (NF) is the most frequent cause of hospital readmission in ambulatory care programs for patients treated with autologous stem cell transplantation (ASCT). We analyzed the impact of intensifying primary prophylaxis with the addition of piperacillin/tazobactam (PT) to FQ. Between January 2002 and August 2018, 154 lymphoma patients conditioned with BEAM were included (40% received ceftriaxone (Ct) plus FQ and 60% PT plus FQ). NF and hospital readmission were required in 84 vs. 41% (p < .0001) and 12 vs. 1% (p = .007) of patients within the Ct and PT groups, respectively. The multivariate analysis showed that PT plus FQ retained its independent protective factor for NF (odds ratio (OR): 0.13; p < .001) and for hospital readmission (OR: 0.07; p = .01). The use of PT and FQ prophylaxis may effectively prevent episodes of NF and hospitalizations in lymphoma patients managed in our at-home ASCT care model.