Resumption Of Therapy Research Articles

P62 USE OF ANTIVIRAL FOR PAUCISINTOMATIC COVID-19 INFECTION IN MULTIPLE MYELOMA PATIENTS UNDERGOING TREATMENT

Patients with multiple myeloma are at increased risk of mortality from COVID-19 infection and show a lower rate of sieroconversion after vaccination and usually late negativization. In this regard, some studies have shown slight changes in mortality during the post-vaccine era. COVID-19 infection, during treatment creates several issues such as discontinuation of active treatment for the disease and a rapid negativization is useful to allow early resumption of therapy. From February 2022, it is possible to set up antiviral treatment with Nirmatrelvir or Molnupiravir in paucisymptomatic patients by reducing hospitalization and evolution in more severe infection. In this study, we collect data on 75 patients with active Multiple Myeloma and COVID-19 infection from Center District (Lazio, Umbria, Marche, Abruzzo) to evaluate the efficacy of this treatment. Of 75 pts, 57 (76%) were in first line of treatment and 18 (24%) in different lines; 62 (82.6%) were treated with antivirals, specifically 49 (65%) with oral antivirals (Nirmartelvir or molnupinavir) and 14 (18.6%) with intravenous antivirals (remdesivir); the remaining 13 (17.4%) patients had no treatment. Of the 62 patients treated with antivirals, 14 (22.6%) were hospitalized for worsening general condition, and 5 (8%) died. This group of patients resolved the infection with swab negativization with a median of 10 days (range 4-72) while the 13 patients who did not undergo any antiviral treatment presented a median of negativization of 15 days. (range 5-20). The majority of patients (67/75 subjects; 89%) had been vaccinated with at least two doses of mRNA vaccine; of these, 54 patients were treated with antivirals presenting a median time to negativization of 9 days compared with 16 days for the unvaccinated and antiviral-treated (P=NS). No difference in hospitalization and mortality. Mortality from COVID-19 infection in the sample was 8% (6/75). In conclusion despite the limitations of the sample size, the use of antivirals in patients with multiple myeloma under active treatment seems to offer a more rapid negativization of the infection promoting a rapid resumption of chemotherapy treatment despite an important effect on mortality and hospitalization. A larger sample will be useful in providing further information on mortality and hospitalization in this patient setting

Surgical treatments for medication-related osteonecrosis of the jaws: advantages and limitations

Objective: The purpose of this paper is to discuss the surgical methods available for the treatment of MRONJ, pointing out their advantages and limitations. Methodology: An integrative review of the literature was performed by searching the PubMed virtual database using the MeSH term "bisphosphonate associated osteonecrosis of the jaw/surgery" and including 26 publications. Results: Surgical intervention is presented as a treatment option in an attempt to reduce disease progression with the recognition that this early intervention may predict beneficial outcomes for the patient. Surgical approaches confer superior treatment outcomes over conservative treatments, with success rates of 80-90% and 10-62%, respectively. To establish treatment, consideration should be given to therapy for removing nonhealing exposed bone, which can be accomplished through curettage, sequestrectomy, and surgical resection. When approaching soft tissue, different flaps can be performed, according to their indications. Conclusion: Surgical treatment has shown maintenance of mucosal coverage, improved quality of life, and quick resumption of antiresorptive therapy for all stages of the disease, with high rates of therapeutic success. However, continued efforts should be encouraged to investigate the best treatment for this pathology.

Secondary prevention after intracerebral haemorrhage.

Intracerebral haemorrhage (ICH) has high mortality in the acute phase and poor functional outcome in the majority of survivors. ICH recurrence is a major determinant of long-term prognosis and is the most feared complication of antithrombotic treatment. On the other hand, ICH patients are at high risk of future ischaemic vascular events. This narrative review provides a critical analysis of the current knowledge on the topic. We performed a Pubmed search with the following terms 'intracerebral haemorrhage', 'stroke', 'outcome', 'secondary prevention', 'anticoagulation' and 'atrial fibrillation', including only English written studies with no time restrictions. Blood pressure management is the cornerstone of secondary ICH prevention, regardless of ICH location or underlying cerebral small vessel disease. Resumption of antiplatelet and anticoagulation therapy is often challenging, with limited evidence from randomized trials. Clinical and imaging predictors can inform the stratification of ICH recurrence risk and might identify patients at very high probability of future haemorrhagic events. This narrative review provides a summary of the main diagnostic tools and therapeutic strategies available for secondary prevention in ICH survivors. Appropriate recognition and treatment of modifiable risk factors for ICH recurrence might improve outcomes in ICH survivors. Ongoing randomized trials might provide novel insights and improve long-term management.

Practice variability in the perioperative management of pediatric moyamoya disease in North America

BackgroundRevascularization surgery decreases the long-term risk of stroke in children with moyamoya but carries an increased risk of perioperative ischemic events. Evidence-based approaches to safe perioperative management of children with moyamoya are limited. We aimed to understand practice variability in perioperative moyamoya care. MethodsNeurologists, neurosurgeons, and intensivists practicing in North America with expertise in perioperative pediatric moyamoya care participated in a 138-item anonymous survey focused on interdisciplinary perioperative care surrounding indirect revascularization surgery. ResultsMany perioperative care practices vary substantially between participants. Timing of resumption of antiplatelet therapy postoperatively, choice of sedative agents and vasopressors, goal blood pressures, rate and duration of intravenous fluid administration, and red blood cell transfusion thresholds are among the most variable practices. ConclusionsThis practice variability survey highlights several important knowledge gaps and areas of equipoise that should be targets for future investigation and consensus-building efforts.

Resumption of anticoagulant therapy after major bleeding and the risk of negative events in patients with atrial fibrillation (based on REGistry of Long-term AnTithrombotic TherApy-2 - REGATA)

It is necessary to strive to resume anticoagulants for patients with atrial fibrillation who have a high risk of thrombosis after the development of large bleeding. Due to the fact that death in these patients is caused not by a recurrence of fatal bleeding, but by the development of stroke in case of refusal of anticoagulant therapy. To evaluate the effect of the resumption of anticoagulant therapy on the risk of recurrence of major bleeding, thrombosis and death in patients with atrial fibrillation who have suffered major bleeding. To evaluate the frequency of bleeding, thrombosis and death in patients with atrial fibrillation after major bleeding according to prospective follow-up data for one year. The recurrence rate of major bleeding after the resumption of therapy was 21.7% per year. The frequency of fatal bleeding was 2.2%. In the anticoagulant withdrawal group, the incidence of thrombotic complications (ischemic stroke and myocardial infarction) was significantly higher compared to patients who resumed therapy. The frequency of death from all causes was significantly higher in the group of patients who did not resume anticoagulant therapy. Half of the deaths were due to cardiovascular causes. The presence of more than 5 points of the Charlson Comorbidity Index was a predictor of the development of the sum of all adverse events. The resumption of anticoagulant therapy after the development of major bleeding in patients with atrial fibrillation reduces the risk of thrombosis and death at a cost, while increasing the risk of recurrence of non-fatal bleeding.

Эффективность и безопасность различных режимов отмены ингибиторов фактора некроза опухоли альфа при длительной ремиссии ювенильного идиопатического артрита без системных проявлений: результаты проспективного простого рандомизированного исследования

Including the tumor necrosis factor TNF inhibitors (TNFi) in the management guidelines for children with juvenile non-systemic juvenile idiopathic arthritis (JIA) has significantly increased the effectiveness of antirheumatic treatment. However, the guidelines of TNFa withdrawal when disease remission is achieved remains unclear. Objective. To study the efficacy and safety of different TNFi withdrawal regimens in patients with juvenile idiopathic arthritis without systemic manifestations due to the achievement of long-term disease remission. Patients and methods: The prospective simple randomized trial included 76 patients with JIA without non-systemic juvenile idiopathic arthritis, with a disease remission duration of ≥24 months, developed under the conditions of treatment with TNFi. Of these, 38.2% are male, the average age is 11.6 years; 67 (88.2%) patients received etanercept (0.8 mg / kg / week. subcutaneously 1 time per week), the rest – adalimumab (24 mg/m2 subcutaneously 1 time in 2 weeks). Depending on the withdrawal regimen, patients were divided into three groups: in the I group, one-time withdrawa was presented, in the II group, the interval between administrations was of two times and the III group was reduced by a dose of two times. The main indicator of the study: preservation of the stage of inactive disease / remission (according to the criteria for remission of C. Wallace) for 6, 12 and 18 months after the withdrawal of TNFi. Results. At the time of withdrawal of TNFi, the average duration of the disease was 7.3 years, the duration of therapy with TNFa was 5 years, remission – was 4.4 years. For 6, 12 and 18 months after the withdrawal of TNFi, the stage of remission persisted in 44 (57.9%), 21 (27.6%) and 18 (23.7%) patients. Exacerbation of disease was registered in 58/76 (76%) patients. Biologic therapy was resumed in 56/58 children, in all cases the stage of inactive disease was reached. Among patients with exacerbation of JIA, 23/56 (41%) continued to receive disease-modifying antirheumatic drugs. Predictors of successful withdrawal of TNFa in patients with non-systemic JIA 6 and 12 months after discontinuation of the biological therapy were the female sex, the absence of HLA B27, antinuclear factor and long-term methotrexate therapy; predictors of exacerbation - increasing in the serum concentration of calprotectin (S-100 protein), the presence of subclinical synovitis according to ultrasound and MRI of the joints and uveitis. Conclusion. After the withdrawal of TNFi, the remission stage for 6 and 12 months persisted more than in half and one third of patients. The withdrawal regimens did not affect the duration of the remission of disease. The resumption of biological therapy in the exacerbation stage of JIA made it possible to reach the remission stage in most patients. Predictors of successful withdrawal of TNFi in patients with non-systemic JIA 6 and 12 months after discontinuation of the biological therapy were the female sex, the absence of HLA B27, antinuclear factor and long-term methotrexate therapy; predictors of exacerbation – increasing in the serum concentration of calprotectin (S-100 protein), the presence of subclinical synovitis according to ultrasound and MRI of the joints and uveitis. The presence of exacerbation predictors makes it impractical the withdrawal of biological therapy due to the high risk of developing an exacerbation of disease. Key words: (TNF)-alpha inhibitors, juvenile idiopathic arthritis, long-term remission, withdrawal predictors, high-sensitivity C-reactive protein (hsCRP), serum calprotectin (S-100 protein)

CTIM-21. NRG-BN010: A SAFETY RUN-IN AND PHASE II STUDY EVALUATING THE COMBINATION OF TOCILIZUMAB, ATEZOLIZUMAB, AND FRACTIONATED STEREOTACTIC RADIOTHERAPY IN RECURRENT GLIOBLASTOMA – TRIAL IN PROGRESS

Abstract BACKGROUND The glioblastoma (GBM) tumor microenvironment (TME) is characterized by a paucity of effector T cells and massive infiltration of immunosuppressive tumor-associated macrophages (TAMs). Inhibition of the interleukin-6 receptor (IL6R) has been demonstrated in preclinical models to repolarize TAMs toward an immunostimulatory phenotype, rendering GBM more susceptible to PD-1/PD-L1 inhibition. Additional preclinical data suggest that fractionated stereotactic radiotherapy (FSRT) can stimulate the release and presentation of tumor-specific antigens, acting as an in-situ vaccine and potentially converting a “cold” TME to a T cell-inflamed state. We designed a safety run-in and phase II study to evaluate the efficacy, safety, and impact on the TME of the combination of IL6R inhibition (tocilizumab), PD-L1 inhibition (atezolizumab), and FSRT in patients with recurrent GBM (rGBM). METHODS NRG-BN010 (NCT04729959) is open to enrollment for adults with rGBM following prior radiotherapy and has 3 components: a safety run-in to determine the recommended phase II dose (RP2D) of the treatment regimen, a phase II single-arm nonsurgical cohort to assess efficacy of the treatment regimen at the RP2D, and a window-of-opportunity surgical cohort. Once the safety run-in (n=12, 3 + 3 design) has determined the RP2D, the phase II and surgical cohorts will open. Phase II patients (n=25, Simon 2-stage design, primary endpoint objective radiographic response) receive an initial pre-FSRT cycle of tocilizumab (plus atezolizumab if included in the RP2D). Within 3-7 days later, the patient receives FSRT (8 Gy x 3 fx), followed by resumption of systemic therapy. Surgical cohort patients (n=16, 1:1 randomization) receive a neoadjuvant cycle of atezolizumab with (n=8) vs. without (n=8) tocilizumab, then FSRT 3-7 days later, then surgical resection 7-14 days after FSRT. Post-operatively, all patients resume systemic therapy at the RP2D. Fresh tumor tissues will be subjected to deep immune profiling to understand the impact of tocilizumab on TAMs in the GBM TME.

RADT-09. PREOPERATIVE STEREOTACTIC RADIOSURGERY FOR LARGE CEREBRAL METASTASES – A PROSPECTIVE CLINICAL TRIAL SHOWING EFFICACY AND DECREASED TIME TO RESUMPTION OF IMMUNOTHERAPY

Abstract INTRODUCTION Preoperative stereotactic radiosurgery (SRS) is an emerging therapeutic strategy for treatment of brain metastasis requiring surgical resection. Prior reports have been highly-controlled, excluding very large brain metastases. Here, we report a prospectively-collected preoperative series reflective of a real-world neurosurgical patient cohort, with a particular focus on resumption of immunotherapy. METHODS Our series included Nf27 prospective preoperative compared to concurrently collected Nf37 postoperative patients. Demographic, SRS volumes/dose, pre/postoperative immunotherapy, and clinical outcomes were collected. Subsequent univariate comparisons between groups were performed. RESULTS Pre/postoperative tumor volumes (19.1 [range: 2.4-65.1] vs. 12.5 [3.6-80.3]cc, p=0.20); local tumor control at 1 year (77.6% vs. 71.4%, p=0.616); overall survival (1.0 [0.8-2.2] vs. 1.3 [0.7-NR] years, p=0.8) were comparable between groups. Rates of LMD (3.7% vs. 8.0%, p=0.39) and subsequent WBRT (8.0% vs. 16.2%, p=0.46) were not statistically different. OR time (168 vs. 173 min, p=0.64), estimated blood loss (133 vs. 180 mL, p=0.31), and wound infections (1 vs. 1, p=1.00) were not significantly different.An ostensible advantage to preoperative SRS is that steroids may be weaned more quickly to allow resumption of immunotherapy. Median steroid taper length was significantly shorter (8 vs. 21.5 days, p=0.007), and median daily Dexamethasone dose at 1 week post-op was significantly lower in the preoperative group (1 vs. 7mg d, p=0.007). All preoperative patients eligible for resumption of immunotherapy (Nf5) resumed treatment within 6 weeks. Conversely, only 2/6 in postoperative patients resumed treatment within 6 weeks, (p=0.07), while 4 failed to resume immunotherapy altogether. In patients initiating immunotherapy after OR/SRS, time to initiation was non-significantly lower in the preoperative group (52[38-84] vs.163[108-208] days, p=0.06). CONCLUSIONS Preoperative SRS is safe and provides comparable local tumor control rate even in large tumors ( >20cc). In patients requiring resumption of immunotherapy, preoperative SRS may provide a faster pathway towards resumption of systemic therapy.

Latent and Active Tuberculosis Infection in Patients with Inflammatory Bowel Disease

Latent tuberculosis (TB) infections (LTBI) impose clinical challenges in terms of the diagnosis and treatment of inflammatory bowel disease (IBD), especially in TB-endemic areas. While steroids and biologics have become increasingly useful in the treatment of patients with moderate-to-severe IBD, the risk of reactivation or developing TB is increased due to their potent immunosuppressive effects. Tumor necrosis factor-alpha inhibition may result in the activation of a latent TB infection, and most cases manifest as more severe forms of disseminated TB. All potential users of immunosuppressive therapy should be screened for LTBI, and appropriate measures for the management of latent and active TB should be undertaken with immediate initiation of anti-TB treatment. Biologics should be withheld during TB treatment, and the proper timing for the resumption of IBD therapy during or after TB treatment should be individualized. This review summarizes the latest knowledge on the risk assessment, detection, and management of latent and active TB infections in patients with IBD.

Systemic manifestations of IgG4-associated disease

The article presents general data on IgG4-associated disease, as well as its classification and universal diagnostic criteria. Attention is focused on the possibility of multi-organ lesions, which complicates diagnosis and treatment. A clinical case of an IgG4-associated disease involving the retroperitoneal space (retroperitoneal fibrosis), lungs (bilateral interstitial pneumonia, diffuse and focal fibroid lung), intestines (chronic colitis) in a middle-aged man is described. Sequential administration of glucocorticoids and monoclonal antibodies made it possible to bring a patient into remission, however, the recurrence of the disease required the resumption of hormone therapy at a reduced dose with a positive effect.

Resumption of Antiplatelet Therapy after Major Bleeding.

Major bleeding is a common threat in patients requiring antiplatelet therapy. Timing and intensity with regard to resumption of antiplatelet therapy represent a major challenge in clinical practice. Knowledge of the patient's bleeding risk, defining transient/treatable and permanent/untreatable risk factors for bleeding, and weighing these against thrombotic risk are key to successful prevention of major adverse events. Shared decision-making involving various disciplines is essential to determine the optimal strategy. The present article addresses clinically relevant questions focusing on the most life-threatening or frequently occurring bleeding events, such as intracranial hemorrhage and gastrointestinal bleeding, and discusses the evidence for antiplatelet therapy resumption using individual risk assessment in high-risk cardiovascular disease patients.

Anticoagulant therapy as a part of secondary stroke prevention in patients with atrial fibrillation

Atrial fibrillation (AF) is the main cause of cardioembolic ischemic stroke (IS), it occurs in 25–35% of patients with IS, and its presence increases the risk of recurrent stroke compared with patients with sinus rhythm. The main method of preventing recurrent IS in AF is the administration of oral anticoagulants (OACs); in non-valvular AF, direct OACs (DOACs) have an advantage. Meta-analysis of randomized clinical trials showed a 19% greater reduction of stroke and systemic embolism risk in the DOACs group compared to warfarin (p<0.0001), including a 51% greater hemorrhagic stroke (HS) risk reduction (p<0.0001). In an additional sub-analysis of the ARISTOTLE trial, patients with AF and a history of stroke/transient ischemic attack showed a significant reduction in the risk of all types of strokes and HS. Although no randomized trial explored the direct comparisons of drugs from the DOACs group, data from observational studies indicate the potential advantage of apixaban in terms of reducing the risk of IS. Russian 2020 clinical guidelines for AF treatment suggest that the resumption/initiation (1–3–12 days) of anticoagulant therapy after an IS should be determined by the decision of a multidis ciplinary team (neurologist, cardiologist, neuroimaging specialist) based on recurrent IS and bleeding risk assessment. According to the 2020 guidelines of the Ministry of Health, the resumption of OACs therapy after an intracranial hemorrhage in patients with AF may be recommended 4–8 weeks after the event, and the decision to reinitiate therapy, as well as after IS, should be made by a multidisciplinary team.

Short versus extended treatment with a carbapenem in patients with high-risk fever of unknown origin during neutropenia: a non-inferiority, open-label, multicentre, randomised trial

Early antibiotic discontinuation has been advocated in haematology patients with fever of unknown origin during chemotherapy-induced neutropenia, but its safety is unknown. We aimed to assess if short treatment with carbapenems is non-inferior to extended treatment. This non-inferiority, open-label, multicentre, randomised trial was done in six hospitals in the Netherlands. Adult patients (≥18 years) who were treated with intensive chemotherapy or haematopoietic stem-cell transplantation (HSCT) for a haematological malignancy, and had fever of unknown origin during high-risk neutropenia (<0·5 × 109/L expected for ≥7 days) were eligible. After onset of fever, patients received either 500 mg intravenous imipenem-cilastatin four times a day or 1000 mg intravenous meropenem three times a day. Between 48 h and 72 h of treatment, participants were randomly assigned (1:1) by a computer-generated sequence to receive a short-term (72 h [60-84]; short treatment group) or extended (≥9 days until being afebrile for 5 days or neutrophil recovery; extended treatment group) carbapenem regimen. The composite primary endpoint was treatment failure, defined as recurrent fever or a carbapenem-sensitive infection between day 4 and day 9 and septic shock or respiratory failure or death from day 4 until neutrophil recovery. The study was designed to assess the non-inferiority of the short treatment compared with the extended treatment regimen, with a non-inferiority margin of 10%. The primary outcome was adjudicated by an independent outcome committee, who were masked to treatment allocation, and was analysed in the intention-to-treat and per-protocol populations. The trial is completed and registered with ClinicalTrials.gov, NCT02149329. Between Dec 1, 2014, and July 1, 2019, 281 patients were included in the intention-to-treat analysis: 144 (51%) patients were assigned to the short treatment group and 137 (49%) to the extended treatment group. Median age was 59 years (IQR 52-65); 109 (39%) patients were women and 172 (61%) were men; 205 (73%) patients received HSCT. In the intention-to-treat analysis, 28 (19%) of 144 patients in the short treatment group versus 21 (15%) of 137 patients in the extended treatment group had treatment failure (adjusted risk difference [ARD] 4·0% [90% CI -1·7% to 9·7%]; p=0·25). In the per-protocol analysis (n=225), 24 (23%) of 104 patients in the short treatment group and 19 (16%) of 121 patients in the extended treatment group had treatment failure (ARD 7·3% [0·3% to 14·9%]; p=0·11). The most common grade 3-5 infection-related adverse events were mucositis (23 [20%] of 114 adverse events in the short treatment group vs 28 [29%] of 98 adverse events in the extended treatment group), fever of unknown origin (20 [18%] vs 16 [16%] events), and bacteraemia (15 [13%] vs 13 [13%] events). The number of serious adverse events were higher in the short treatment group (23 [16%] of 144 patients) than in the extended treatment group (14 [10%] of 137 patients), due to an increased rate of readmission (17 [12%] patients in the short treatment group vs ten [7%] in the extended treatment group). Death before 30 days after neutrophil recovery occurred in five (3%) participants in the short treatment group: two due to progressive leukaemia, two due to candidaemia, and one due to Enterococcus faecium bacteraemia and drug-induced pneumonitis. One (1%) patient died in the extended treatment group due to candidaemia. None of the deaths were related to carbapenem-sensitive infections. Early discontinuation of carbapenem treatment in patients with febrile neutropenia of unknown origin does not result in increased treatment failure. Our study supports short treatment if patients are afebrile after 3 days of carbapenem treatment. However, because secondary analyses suggested that serious adverse events and all-cause mortality occurred more often in patients who are persistantly febrile the short treatment group, we recommend vigilance for non-susceptible pathogens and early resumption of empirical therapy in patients who are deteriorating. The Netherlands Organisation for Health Research and Development and Fonds NutsOhra.

The long and short of antibiotic management for neutropenic fever in patients with haematological malignancy

Neutropenic fever is a common complication of therapy for haematological malignancy and in about 40% of episodes, no clinical focus or microbiological cause is identified. 1 Verlinden A Jansens H Goossens H et al. Safety and efficacy of antibiotic de-escalation and discontinuation in high-risk hematological patients with febrile neutropenia: a single-center experience. Open Forum Infect Dis. 2022; 9ofab624 Crossref PubMed Scopus (6) Google Scholar , 2 Averbuch D Orasch C Cordonnier C et al. European guidelines for empirical antibacterial therapy for febrile neutropenic patients in the era of growing resistance: summary of the 2011 4th European Conference on Infections in Leukemia. Haematologica. 2013; 98: 1826-1835 Crossref PubMed Scopus (343) Google Scholar , 3 Aguilar-Guisado M Espigado I Martín-Peña A et al. Optimisation of empirical antimicrobial therapy in patients with haematological malignancies and febrile neutropenia (How Long study): an open-label, randomised, controlled phase 4 trial. Lancet Haematol. 2017; 4: e573-e583 Summary Full Text Full Text PDF PubMed Scopus (93) Google Scholar The optimal strategy for antibiotic management in the setting of neutropenic fever with no identified source is yet to be defined. Common strategies include early de-escalation from empiric therapy to antibiotic prophylaxis until neutrophil recovery or complete cessation of antibiotic therapy with different cessation thresholds used. 2 Averbuch D Orasch C Cordonnier C et al. European guidelines for empirical antibacterial therapy for febrile neutropenic patients in the era of growing resistance: summary of the 2011 4th European Conference on Infections in Leukemia. Haematologica. 2013; 98: 1826-1835 Crossref PubMed Scopus (343) Google Scholar , 4 Freifeld AG Bow EJ Sepkowitz KA et al. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of america. Clin Infect Dis. 2011; 52: e56-e93 Crossref PubMed Scopus (2014) Google Scholar A cellular recovery threshold (neutrophil count ≥0·5×109/L) for cessation has been recommended, 4 Freifeld AG Bow EJ Sepkowitz KA et al. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of america. Clin Infect Dis. 2011; 52: e56-e93 Crossref PubMed Scopus (2014) Google Scholar but, new data suggest the use of clinically guided cessation using clinical stability and resolution of fever for earlier antibiotic cessation. 1 Verlinden A Jansens H Goossens H et al. Safety and efficacy of antibiotic de-escalation and discontinuation in high-risk hematological patients with febrile neutropenia: a single-center experience. Open Forum Infect Dis. 2022; 9ofab624 Crossref PubMed Scopus (6) Google Scholar , 3 Aguilar-Guisado M Espigado I Martín-Peña A et al. Optimisation of empirical antimicrobial therapy in patients with haematological malignancies and febrile neutropenia (How Long study): an open-label, randomised, controlled phase 4 trial. Lancet Haematol. 2017; 4: e573-e583 Summary Full Text Full Text PDF PubMed Scopus (93) Google Scholar Earlier antibiotic cessation compared with continuation until resolution of neutropenia is associated with lower antibiotic exposure and no significant difference in rates of clinical failure, safety, or mortality. 1 Verlinden A Jansens H Goossens H et al. Safety and efficacy of antibiotic de-escalation and discontinuation in high-risk hematological patients with febrile neutropenia: a single-center experience. Open Forum Infect Dis. 2022; 9ofab624 Crossref PubMed Scopus (6) Google Scholar , 3 Aguilar-Guisado M Espigado I Martín-Peña A et al. Optimisation of empirical antimicrobial therapy in patients with haematological malignancies and febrile neutropenia (How Long study): an open-label, randomised, controlled phase 4 trial. Lancet Haematol. 2017; 4: e573-e583 Summary Full Text Full Text PDF PubMed Scopus (93) Google Scholar Short versus extended treatment with a carbapenem in patients with high-risk fever of unknown origin during neutropenia: a non-inferiority, open-label, multicentre, randomised trialEarly discontinuation of carbapenem treatment in patients with febrile neutropenia of unknown origin does not result in increased treatment failure. Our study supports short treatment if patients are afebrile after 3 days of carbapenem treatment. However, because secondary analyses suggested that serious adverse events and all-cause mortality occurred more often in patients who are persistantly febrile the short treatment group, we recommend vigilance for non-susceptible pathogens and early resumption of empirical therapy in patients who are deteriorating. Full-Text PDF

Moderate Colitis Not Requiring Intravenous Steroids Is Associated with Improved Survival in Stage IV Melanoma after Anti-CTLA4 Monotherapy, But Not Combination Therapy.

BackgroundFor patients with melanoma, gastrointestinal immune-related adverse events are common after receipt of anti-CTLA4 therapy. These present difficult decision points regarding whether to discontinue therapy. Detailing the situations in which colitis might predict for improved survival and how this is affected by discontinuation or resumption of therapy can help guide clinical decision-making.Materials and MethodsPatients with stage IV melanoma receiving anti-CTLA4 therapy from 2008 to 2019 were analyzed. Immune-related colitis treated with ≥50 mg prednisone or equivalent daily or secondary immunosuppression was included. Moderate colitis was defined as receipt of oral glucocorticoids only; severe colitis was defined as requiring intravenous glucocorticoids or secondary immunosuppression. The primary outcome was overall survival (OS).ResultsIn total, 171 patients received monotherapy, and 91 received dual checkpoint therapy. In the monotherapy group, 25 patients developed colitis and a nonsignificant trend toward improved OS was observed in this group. Notably, when colitis was categorized as none, moderate or severe, OS was significantly improved for moderate colitis only. This survival difference was not present after dual checkpoint therapy. There were no differences in known prognostic variables between groups, and on multivariable analysis neither completion of all ipilimumab cycles nor resumption of immunotherapy correlated with OS, while the development of moderate colitis did significantly affect OS.ConclusionThis single-institution retrospective series suggests moderate colitis correlates with improved OS for patients with stage IV melanoma treated with single-agent anti-CTLA4, but not dual agent, and that this is true regardless of whether the immune-checkpoint blockade is permanently discontinued.

Illustration of exacerbating cortical superficial siderosis on close-up MRIs after resumption of anticoagulant therapy. (P15-10.009)

Illustration of exacerbating cortical superficial siderosis on close-up MRIs after resumption of anticoagulant therapy. (P15-10.009)

B-14 | Time to Resumption of Cancer Therapy while using Different Stent Types in Cancer Patients Undergoing Percutaneous Coronary Intervention

The goal of revascularization in cancer patients undergoing PCI is not only to treat underlying coronary disease but to also allow timely resumption of cancer therapy (CaTX). We sought to evaluate time to resumption of CaTX in cancer patients while using different stent types including bare metal stents (BMS), drug eluting stents (DES) and nano coated COBRA stents.

Detectable Serum Concentration with Prophylactic Inhaled Tobramycin in Lung Transplant Recipients

<h3>Purpose</h3> Inhaled tobramycin (iTOBI) is used in bilateral lung transplant recipients (LTRs) to prevent PsA colonization. Pharmacokinetic studies show that iTOBI is not systemically absorbed, making it an alternative to intravenous formulations. Case reports exist of LTRs on iTOBI developing renal failure with detectable tobramycin troughs (DTTs). The purpose of this review is to describe the incidence of DTT in LTRs receiving iTOBI immediately post-transplant. <h3>Methods</h3> This single-center, retrospective review included patients in their index lung transplant admission who received iTOBI with a DTT (≥ 0.5 mg/L). All LTRs received iTOBI 300 mg q12hr prophylaxis for at least one month with levels drawn for cause when concerned for accumulation. Primary outcome was the number of LTRs with DTTs. Secondary outcomes included duration of therapy and incidence of SCr increase ≥ 0.3 mg/dL within 48 hours (AKI). Descriptive statistics were used to analyze baseline characteristics and outcomes. <h3>Results</h3> We reviewed 211 LTRs from January 2014 to August 2021. Twenty patients (9.5%) met inclusion criteria with 32 DTTs and 4 were excluded due to undetectable troughs. Median time to initial DTT was 10 (2-34) days of therapy. AKI occurred within a week prior to 84% of DTT, with a median of 3 days to elevated trough. Median time to DTT clearance (undetectable level or resumption of therapy) was 2 days. Therapy was discontinued in 10% of patients due to concern for nephrotoxicity (Table 1). <h3>Conclusion</h3> iTOBI therapy may cause systemic drug levels in the early post-transplant phase. Given known association of systemic tobramycin with nephrotoxicity, particularly in the presence of nephrotoxic medications, iTOBI trough surveillance may be prudent to guide therapy. Rapid DTT clearance may render repeat levels unnecessary. Larger studies are needed to assess the renal risk, timing of iTOBI accumulation in LTRs and thresholds for serum monitoring.

Use Of Sacubitril/valsartan In Patients With Cardiogenic Shock On Inotropic Support

Introduction The initiation of sacubitril/valsartan (S/V) after hemodynamic stabilization in patients hospitalized for acute decompensated heart failure has been shown to be safe and effective. There are limited data suggesting that S/V is safe in patients in cardiogenic shock. The optimal timing of initiation or resumption of therapy remains uncertain. Hypothesis S/V is safe and tolerable for patients in cardiogenic shock requiring inotropic support. Methods We identified patients with an ICD 9/10 code diagnosis of heart failure with reduced ejection fraction who had been admitted to the cardiac intensive care unit of a quaternary care medical center between January 1, 2017 and December 31, 2020. Within this cohort, we identified 19 patients who were treated with S/V while receiving inotropic support. Demographics and clinical characteristics (laboratory results and invasive hemodynamics) were collected. Opening hemodynamics were obtained within 24 hours of admission and closing hemodynamics were obtained after weaning off or selecting a stable discharge dose of inotrope. Differences between clinical characteristics were compared using paired Wilcoxon signed rank tests. Results 19 patients (100%) received milrinone and 3 patients (15.8%) additionally received dobutamine during their hospitalization. Cardiac index increased from 1.70 L/min/m2 [interquartile range [IQR], 1.50-2.20 L/min/m2] to 2.50 L/min/m2 ([IQR, 2.20-2.70 L/min/m2]; p<0.001) and systemic vascular resistance decreased from 1490 dynes/sec/cm5 [IQR, 1340-1741 dynes/sec/cm5] to 945 dynes/sec/cm5 ([IQR, 864-1102 dynes/sec/cm5]; p<0.001). Serum creatinine and potassium remained stable from admission to discharge (p for both > 0.05). At discharge, 14 patients (73.7%) were prescribed S/V. Of the patients discharged on S/V, 5 (35.7%) were also discharged on milrinone. S/V was discontinued prior to discharge due to hypotension in 4 patients (21.1%) and acute kidney injury in 1 patient (5.3%). At 3 months post-discharge, a majority of patients (68.4%) remained on S/V. Conclusions Patients in cardiogenic shock requiring inotropic support can safely receive S/V without a significant increase in serum creatinine or potassium. Further analyses of larger cohorts should explore the ideal timing for initiating or resuming S/V in patients receiving inotropic support. Establishing the safety and tolerability of this practice may lead to earlier adoption and/or decreased interruption of guideline directed medical therapy. The initiation of sacubitril/valsartan (S/V) after hemodynamic stabilization in patients hospitalized for acute decompensated heart failure has been shown to be safe and effective. There are limited data suggesting that S/V is safe in patients in cardiogenic shock. The optimal timing of initiation or resumption of therapy remains uncertain. S/V is safe and tolerable for patients in cardiogenic shock requiring inotropic support. We identified patients with an ICD 9/10 code diagnosis of heart failure with reduced ejection fraction who had been admitted to the cardiac intensive care unit of a quaternary care medical center between January 1, 2017 and December 31, 2020. Within this cohort, we identified 19 patients who were treated with S/V while receiving inotropic support. Demographics and clinical characteristics (laboratory results and invasive hemodynamics) were collected. Opening hemodynamics were obtained within 24 hours of admission and closing hemodynamics were obtained after weaning off or selecting a stable discharge dose of inotrope. Differences between clinical characteristics were compared using paired Wilcoxon signed rank tests. 19 patients (100%) received milrinone and 3 patients (15.8%) additionally received dobutamine during their hospitalization. Cardiac index increased from 1.70 L/min/m2 [interquartile range [IQR], 1.50-2.20 L/min/m2] to 2.50 L/min/m2 ([IQR, 2.20-2.70 L/min/m2]; p<0.001) and systemic vascular resistance decreased from 1490 dynes/sec/cm5 [IQR, 1340-1741 dynes/sec/cm5] to 945 dynes/sec/cm5 ([IQR, 864-1102 dynes/sec/cm5]; p<0.001). Serum creatinine and potassium remained stable from admission to discharge (p for both > 0.05). At discharge, 14 patients (73.7%) were prescribed S/V. Of the patients discharged on S/V, 5 (35.7%) were also discharged on milrinone. S/V was discontinued prior to discharge due to hypotension in 4 patients (21.1%) and acute kidney injury in 1 patient (5.3%). At 3 months post-discharge, a majority of patients (68.4%) remained on S/V. Patients in cardiogenic shock requiring inotropic support can safely receive S/V without a significant increase in serum creatinine or potassium. Further analyses of larger cohorts should explore the ideal timing for initiating or resuming S/V in patients receiving inotropic support. Establishing the safety and tolerability of this practice may lead to earlier adoption and/or decreased interruption of guideline directed medical therapy.

Тактика возобновления лечения пациентов с неоваскулярной возрастной макулярной дегенерацией после перерыва антиангиогенной терапии

Purpose. To determine the preferred strategy for resuming treatment in patients with neovascular agerelated macular degeneration after interruption of anti-angiogenic therapy due to COVID-19 pandemic. Material and methods. Seventy patients (80 eyes, 52 men and 18 women, mean age 73.1 ± 9.6 years) with nAMD of the first and second year of treatment, who interrupted the course of antiangiogenic intravitreal therapy due to restrictions due to the COVID-19 pandemic were included, as well as the group of the first year of treatment, without violation of the treatment regimen. When therapy was resumed, patients of the second year received treatment in the “fixed dosing” regimen (1 time in 2 months), or in an “pro re nata” regimen. Patients of the first year continued treatment in a “fixed dosing” regimen. All patients before the initiation of the treatment, before and after treatment interruption, and also 6 months after the resumption of anti-angiogenic therapy, received a standard ophthalmic examination and optical coherence tomography. Results. Six months after resuming of antiangiogenic therapy, functional parameters in patients of the “fixed dosing” regimen and “pro re nata” did not differ significantly (p = 0.85), with a decrease in the number of injections by 30% in the subgroup of the “pro re nata” regimen (p = 0.0001). A long interruption in the first year of nAMD treatment does not allow for a significant increase in visual acuity even when using the most effective “fixed” regimen when therapy is resumed. Conclusion. For patients with nAMD of the second year of treatment “pro re nata” regimen allows performing fewer intravitreal injections comparable to the “fixed dosing” regimen with similar functional results. Treatment interruption during the first year of the treatment precludes achieving a significant improvement in visual acuity even with “fixed dosing” regimen. Keywords: neovascular age-related macular degeneration, anti-VEGF therapy, aflibercept, optical coherence tomography, treatment interruption, COVID-19.