Resumption Of Therapy Research Articles

Resumption of Anticoagulant Therapy in a Severe Trauma Patient with a Mechanical Aortic Valve Replacement

Resumption of Anticoagulant Therapy in a Severe Trauma Patient with a Mechanical Aortic Valve Replacement

PS1163 PATIENT‐BASED PROSPECTIVE REAL WORLD DATA ANALYSIS SHOWS THAT THE DURATION OF TREATMENT INTERRUPTIONS WITH SUBSEQUENT RESUMPTION OF IDELALISIB THERAPY CAN VARY FROM DAYS TO MONTHS

Background:Idelalisib, a first‐in‐class PI3Kδ‐inhibitor, is licensed in the European Union in relapsed chronic lymphocytic leukemia (CLL) and refractory follicular lymphoma (FL). Treatment should be continued until disease progression or unacceptable toxicity and may continue for several months or years. Optimal therapy management is therefore important and may include temporary treatment interruptions (TIs) and dose modifications to manage idelalisib associated adverse drug reactions (ADRs).Aims:Recent data from a retrospective analysis of idelalisib clinical studies suggest that patients may benefit from optimal ADR management of idelalisib via TI and subsequent resumption of therapy [Ma et al. ASH 2018]. Here we analyzed frequency and duration of TIs within a prospective observational study. To understand the effect of TIs on the course of disease, we additionally analyzed lymphocyte counts during and after treatment interruption on an individual patient level.Methods:Post‐hoc analysis of a prospective, two‐cohort, multicenter, non‐interventional post‐authorization safety study (PASS) reporting real world safety and effectiveness data on the use of idelalisib in Germany. Inclusion of patients was based on the physician's decision to initiate treatment with idelalisib in accordance with the European Summary of Product Characteristics. Detailed methods, patient characteristics and results were already published at two conferences [Hoechstetter et al. DGHO 2018; Hoechstetter et al. ASH 2018]. Descriptive statistics were used for data analysis. Idelalisib TIs were defined as documented interruptions with subsequent resumption of idelalisib therapy.Results:96 patients (84 CLL and 12 FL patients) enrolled at 45 sites were included until data cut in February 2018 with a median follow‐up of 9.7 months. 58 patients had documented permanent discontinuation of idelalisib therapy. 49 patients had one or more documented TIs with 26 patients (one TI n = 20, two TI n = 6) subsequently resuming therapy. After interruptions, treatment was resumed with the standard or a reduced idelalisib dose of 150 mg or 100 mg twice daily, respectively. The most frequently reported reason for both dose reduction and TI was ADR, only 9 TIs followed an adverse event (AE) not related to idelalisib. The 3 most commonly reported ADRs (events) resulting in TI were diarrhea (9), pulmonary complications (4) and rash (3). The duration of TIs varied widely from only a few to 235 days. The median (range) duration of a single TI was 15 (1–235) days, representing 15 (1–86) days for the first and 16 (5–235) days for the second interruption, respectively. 9 patients had a single interruption with a duration of >30 days. Patient level data demonstrate stable or only moderate changes in lymphocyte counts during this treatment interruption.Summary/Conclusion:Optimal management of idelalisib therapy to achieve best outcomes for patients may include temporary TIs and/or dose modifications. However, little information is available about the duration of idelalisib TIs and the possibility to resume therapy in routine clinical practice. Our analysis of prospectively collected real world data shows that the duration of TIs may vary widely from a few days to several months with about 50% of patients with a TI resuming idelalisib therapy. Patient level data suggest that lymphocyte counts were relatively stable during and after TIs. Our results therefore provide evidence that idelalisib treatment may be interrupted to allow treatment of ADRs/AEs with subsequent resumption of idelalisib therapy.image

Immune-mediated colitis after resumption of immune checkpoint inhibitor therapy.

2577 Background: Immune checkpoint inhibitor (ICI) therapy is often suspended because of immune-mediated diarrhea and colitis (IMDC). We examined the recurrence rate and risk factors for IMDC after ICI resumption. Methods: This retrospective multicenter study examined patients who resumed ICI therapy after improvement of IMDC between 1/2010 and 11/2018. Univariate and multivariate logistic regression analyses assessed the association of clinical covariates and IMDC recurrence. Results: Of the 167 patients in our analysis, 32 resumed an anti-CTLA-4 agent and 135 an anti-PD-1/L1 agent. The median duration from IMDC to restart of ICI treatment was 49 days (IQR, 23-136). IMDC recurred in 57 (34%) patients overall (44% of those resuming an anti–CTLA-4 and 32% resuming an anti–PD-1/L1 agent); 47 of these patients (82%) required immunosuppressive therapy for recurrent IMDC (Table). The median duration from ICI resumption to IMDC recurrence was 53 days (IQR 22-138). On multivariate logistic regression, patients who received anti-PD-1/L1 therapy at initial IMDC had a higher risk of IMDC recurrence (odds ratio [OR], 3.45, 95%CI, 1.59-7.69; P<0.01). Risk of IMDC recurrence was higher for patients who required immunosuppression for initial IMDC (OR, 3.22; 95%CI, 1.08-9.62; P=0.02) or had longer duration of IMDC symptoms in the initial episode (OR, 1.01; 95%CI, 1.00-1.03; P=0.03). Risk of IMDC recurrence was lower for those who resumed anti–PD-1/L1 therapy than for those who resumed anti–CTLA-4 therapy (OR, 0.30; 95%CI, 0.11-0.81; P=0.02). Conclusions: One-third of patients who resumed ICI treatment after IMDC experienced recurrent IMDC. IMDC recurrence was less frequent after resumption of anti–PD-1/L1 than after anti–CTLA-4. Characteristics of recurrent IMDC based on resumed ICI therapy. [Table: see text]

Reversal and Resumption of Antithrombotic Therapy in LVAD-Associated Intracranial Hemorrhage

Little data exist regarding reversal and resumption of antithrombotics after left ventricular assist device (LVAD)-associated intracranial hemorrhage. Prospectively collected data of LVAD patients with intracranial hemorrhage were reviewed. Coagulopathy reversal agents, antithrombotic regimens, and thrombotic (venous thromboembolism, ischemic stroke, myocardial infarction) and hemorrhagic (recurrent intracranial hemorrhage, gastrointestinal bleed, anemia requiring transfusion) complications were recorded. Of 405 patients, intracranial hemorrhage occurred in 39 (10%): 23 intracerebral hemorrhages, 10 subarachnoid hemorrhages, and 6 subdural hematomas. Of 27 patients who received antithrombotic reversal, 8 (30%) had inadequate coagulopathy reversal, and 3 of these patients had hemorrhage expansion or died before repeat imaging. One (4%) patient had a thrombotic complication (deep vein thrombosis). Antithrombotic therapy was resumed in 17 (100%) survivors in a median time 8 days for antiplatelet agents and 14 days for warfarin. Recurrent intracranial hemorrhage occurred within a median of 7 days of antithrombotic resumption, while ischemic stroke occurred in a median of 428 days. Patients who resumed antiplatelets alone (n= 4) had a trend toward more thrombotic events (1.37 versus 0.14 events/patient-year [EPPY]; p=0.08), including more fatal thrombotic events (0.34 EPPY versus 0.08 EPPY; p= 0.89) compared with thoseresuming warfarin ± antiplatelet (n= 14). Nonfatal hemorrhage event rates were 0.34 EPPY in thewarfarin ± antiplatelet versus 0 EPPY in the antiplatelet-alone group (p= 0.16). No fatal hemorrhagic events occurred. Reversal of anticoagulation appears safe after LVAD-associated intracranial hemorrhage, though inadequate reversal was common. Resumption of warfarin ± antiplatelet was associated with fewer fatal and nonfatal thrombotic events compared with antiplatelets alone, though more nonfatal hemorrhage events occurred.

Resumption of anticoagulant therapy after anticoagulant-related gastrointestinal bleeding: A systematic review and meta-analysis

IntroductionOral anticoagulation (OAC) is permanently discontinued in up to 50% of patients following a gastrointestinal (GI) bleed. A previous meta-analysis showed a reduced risk of thromboembolism and death, and a non-statistically significant increased risk of re-bleeding associated with resumption. We conducted an updated meta-analysis to determine the risks of recurrent GI bleeding, thromboembolism, and death in patients who resumed OAC compared to those who did not. Materials and methodsWe searched EMBASE, MEDLINE, and the Cochrane Central Register of Controlled Trials for new references from January 2014 to September 2017. Randomized controlled trials and observational studies involving adults with OAC-related GI bleeding were included. Risk of bias was assessed using the Cochrane Collaboration's ROBINS-I tool. Pooled relative risk (RR) ratios were calculated using a random-effects model. ResultsWe identified 12 observational studies involving 3098 patients. There was an increased risk of recurrent GI bleeding (RR 1.91, 95% CI 1.47–2.48, I2 = 0%, 11 studies), and a reduced risk of thromboembolism (RR 0.30, 95% CI 0.13–0.68, I2 = 59.8%, 9 studies) and death (RR 0.51, 95% CI 0.38–0.70, I2 = 71.8%, 8 studies) in patients who resumed OAC compared to those who did not. Eleven studies were judged to be at serious risk of bias due to confounding. ConclusionsResuming OAC after OAC-related GI bleeding appears to be associated with an increase in recurrent GI bleeding, but a reduction in thromboembolism and death. Further prospective data are needed to identify patients for whom the net clinical benefit favours OAC resumption and the optimal timing of resumption.

The effect of tyrosine kinase inhibitor interruption and interferon use on pregnancy outcomes and long-term disease control in chronic myeloid leukemia

The management of CML in pregnancy is challenging with the need to balance disease control against potential teratogenic effects of TKI therapy. In this multi-center case-cohort study of 16 women in chronic phase, CML ceased TKI treatment pre- or post-conception during their first pregnancy. Thirteen patients were on imatinib; 9 ceased their TKI prior to conception and 7 ceased at pregnancy confirmation. Twelve patients had achieved either MMR or better at time of TKI cessation. Eleven women lost MMR during pregnancy and two patients lost CHR. Fourteen women reestablished MMR on TKI recommenced. The depth molecular response prior to conception appeared to correlate well with restoration of disease control on TKI recommencement though duration of MMR did not appear to be as important. While interruption of TKI treatment for pregnancy usually leads to loss of molecular response, loss of hematological response is uncommon and disease control is reestablished with resumption of therapy in the majority of women.

Safety and Efficacy of Long Term Suppression of PI3Kinase Pathway By Small Molecule PI3K-Delta Inhibitor, Leniolisib in Apds (Activated PI3Kδ Syndrome)

▪Inherited gain-of-function mutations in PIK3CD encoding PI3Kδ (phosphoinositide 3-kinase delta) lead to accumulation of senescent T cells, lymphadenopathy, splenomegaly and immune-deficiency (Activated PI3Kδ Syndrome, APDS). Clinical manifestations include multilineage cytopenias and susceptibility to B cell Non-Hodgkins Lymphoma.We recently reported use of leniolisib (CDZ173), a novel, potent and selective oral PI3Kd inhibitor in six APDS patients in a 12-week, open-label, multi-center, within-subject dose-escalation study (Rao et al, Blood 23 November 2017). Leniolisib was safe and well tolerated and led to a dose-dependent reduction in PI3K/AKT pathway activity and improved the immune dysregulation with normalization of circulating transitional and naïve B cells and reduction in PD-1+CD4+ and senescent CD57+CD8+ T cells. Elevated serum IgM and other biomarkers including IFNg, TNF, CXCL13 and CXCL10 normalized or decreased with leniolisib. Cytopenias and lymphoproliferation improved in all patients with index lymph node sizes and spleen volumes reduced by 39% and 40%, respectively.Here we report the long term follow up safety and efficacy data in all six patients (Table 1) who have continued treatment with leniolisib in an extension study at 70 mg b.i.d (ClinicalTrials.gov number NCT02859727). These patients have been treated for up to 949 days (as of July 20th 2018). Three of them were lymphoma survivors. Three patients were treated with rapamycin prior to starting leniolisib. No patient in the 12-week clinical trial or in the long term extension study has experienced any significant adverse events. Notably, side effects prevalent with mTOR or other PI3K inhibitors such as diarrhea/colitis, skin rashes, susceptibility to infections or liver enzyme elevation were absent. Three patients have stopped immunoglobulin supplementation as a reflection of the normalization of their B cell function. Cytopenias, including anemia, thrombocyopenia, neutropenia and lymphopenia have continued to improve. (Figure 1: Showing representative improvement of laboratory data including normalization of IgM for patient 002, following 18 months of treatment with leniolisib; Figure2: Showing improvement of lymphoproliferation in CT scans from 2016 and 2018 for Patient 003. This patient stopped leniolisib for 15 months from October 2016 until January 2018 leading to worsening lymphoproliferation that improved promptly on resumption of therapy). Available data on longterm safety, effects on lymphoproliferation and immune dysregulation in the ongoing leniolisib extension study will be shared during the meeting.The results support safe and efficacious long term inhibition of PI3Kδ protein as a new targeted therapeutic approach in APDS and other disorders of nonmalignant lymphopoliferation associated with hyperactive PI3Kinase pathway. [Display omitted] DisclosuresRao:novartis: Research Funding. Dalm:Novartis: Research Funding. Sediva:Novartis: Research Funding. van Hagen:Novartis: Research Funding. Cabanski:Novartis: Employment. Valentin:Novartis: Employment. de Buck:Novartis: Employment. Kalis:Novartis: Employment. Hasselberg:Novartis: Employment. Burkhart:Novartis: Employment. Kucher:Novartis: Employment. Sloth:Novartis: Employment. Uzel:Novartis: Research Funding.

Effectiveness of resuming ustekinumab therapy in psoriasis patients with metabolic disorders. Clinical experience

Psoriasis is a chronic immune-mediated inflammatory skin disease with possible damage to the musculoskeletal system, affecting 2-3 % of the adult population of the planet. To date, special attention in the treatment of psoriasis is paid to the comorbid background, since it is known that it can aggravate the course of psoriasis and affect the effectiveness of therapy. The purpose of psoriasis therapy is to achieve clean or almost clean skin, sustainable improvement of psoriatic arthritis, improving the quality of life, all this became possible with the advent of genetically engineered biological drugs. However, in the treatment of genetically engineered biological drugs there are “pain points”: primary inefficiency, “the effect of slipping”, the scheme of transition from one drug to another, the safety of the combined use of GIBP and system-based drugs, interruption of therapy.Objective. To study the therapeutic efficacy of ustekinumab in psoriasis patients with forced interruption of treatment, taking into account metabolic disorders.Materials and methods. 52 patients with a diagnosis of plaque psoriasis receiving ustekinumab for 3 years were under observation, which were divided into 2 groups, depending on body weight and metabolic disorders.Results. More than 80 % of patients taking the drug at a dosage of 45 mg, and at a dosage of 90 mg, to week 12 therapy reached PASI 75. By week 24, the proportion of patients in group I who reached PASI 75 was 96.3 %, in group II — 88.0 %.By week 48 PASI 75 reached 90.4 % patients: in group I — 100 % patients, in group II — 80.0 % patients.At 76 weeks, patients were interrupted ustekinumab treatment in connection with the purchase of the drug. The duration of treatment interruption ranged 36 weeks. By week 112, 86.5 % patients in both groups had a relapse of psoriasis, which was assessed by the loss of the therapeutic response of PASI 75.By week 124 (12 weeks after the resumption of therapy) 82.7 % patients reached PASI 75: in group I — 92.6 % patients, in group II — 72.0 % patients.After 16 weeks (week 128), all patients 100 % achieved PASI 75 IN group I. In group II to week 128 PASI 75 was observed in 80 % patients.Conclusion. With the resumption of treatment of patients with psoriasis with ustekinumab after a long interruption, there is a rapid and complete restoration of therapeutic effectiveness, however, in patients with psoriasis with metabolic disorders, there is a decrease in efficiency after the resumption of therapy in comparison with patients without abdominal obesity, which can determine the further strategy and tactics of management of such patients.

Antithrombotic Therapy after Bleeding in Elderly Polimorbid Patient: Our Time Challenge

In recent years, there has been a clear trend towards an increase in the number of elderly patients suffering from several polymorbid diseases, which considerably complicates the forecast and tactics of management. A clinical case of an elderly patient, suffering for a long time from type 2 diabetes mellitus, receiving insulin and treated with programmed hemodialysis due to terminal chronic renal failure, and suffering from atrial fibrillation in permanent form, is presented. The patient was hospitalized in theCityClinicalHospital№1 named after N.I. Pirogov due to acute repeated myocardial infarction. An emergency percutaneous coronary intervention was performed, the infarct-dependent artery was stented with a drug-eluted stent. The postoperative period complicated by the development of acute blood loss associated with bleeding from the upper sections of the gastrointestinal tract, and severe anemia of the combined genesis (posthemorrhagic, renal). This situation required doctors to make non-standard decisions in the choice of antithrombotic therapy. This clinical case illustrates the difficulties in elderly polymorbid patient management in real clinical practice and the controversial issues arising in the prescribing the antithrombotic therapy, especially after bleeding had developed. The supporting guidelines cannot answer all the questions which the daily practice poses to the doctor. In each case, the resumption of antithrombotic therapy and its optimal choice for an elderly polymorbid patient with developed bleeding is the subject of discussion and presented a real challenge for the treating physician.

Prevention of surgical site infection via antibiotic administration according to guidelines after gynecological surgery.

We modified the antimicrobial prophylaxis of surgical site infection (SSI) according to the guidelines of the Japanese Society of Chemotherapy and Japan Society of Infectious Diseases (hereinafter referred to as optimization) and measured outcomes. From April 2016 to March 2017, we performed cesarean section and open hysterectomy with optimization, and compared the outcome to that of surgery performed without optimization between April 2014 and March 2016. We measured the rates of antibiotic discontinuation, appropriate antibiotic selection, SSI incidence, resumption of antibiotic therapy and fever incidence, as well as the length of postoperative hospital stay and medical expenses for antibiotics to evaluate the appropriateness and outcomes of antibiotic prophylaxis. Optimization resulted in a change in the method of selecting antibiotics for cesarean section, but there was no change in SSI incidence rate (0.74% vs 0.0%, P = 0.36). Optimization reduced the use of antibiotics and medical expenses of hysterectomy (median reduction of 50% and 78% for hysterectomy without or with lymphadenectomy, respectively). However, there was no change in outcome regarding SSI incidence (5.7% vs 0.0%, P = 0.11 and 7.8% vs 9.5%, P = 0.77, respectively). Appropriate use of antibiotics according to guidelines reduced antibiotic dose and medical expenses, but there was no change in outcome regarding SSI incidence rate. These findings suggested that implementation of dosing regimens according to the guidelines would be useful to reduce antibiotic medicine costs and prevent resistant bacteria and complications associated with antibiotics.

Management of Upper Gastrointestinal Bleeding by an Internist

Nonvariceal upper gastrointestinal bleeding (UGIB) carries high morbidity and mortality, which can be lowered by timely evaluation and management. This article presents a comprehensive literature review and current guidelines for the management of nonvariceal UGIB by an internist. Pre-endoscopic management includes optimal resuscitation, and making a decision about holding the anticoagulation and antiplatelet therapy versus continuation due to risk of thrombosis. Proton pump inhibitors (PPIs) are beneficial for both ulcer and nonulcer diseases as they reduce the risk of re-bleeding by clot stabilization. Endoscopy should only be performed after hemodynamic stability has been achieved and should not be delayed by more than 24 hours. Resumption of anticoagulation and antiplatelet therapy is based on endoscopic findings and thromboembolic risk. The patient should be discharged on PPIs and should be followed up by a primary care physician.

766 RESUMPTION OF ANTITHROMBOTIC THERAPY AFTER ROUTINE ENDOSCOPY: PHYSICIAN DOCUMENTATION AND PATIENT OUTCOMES

Management of antiplatelet (AP) and anticoagulant (AC) agents before and after endoscopic procedures is a common dilemma. Failure to resume AP/AC agents is associated with increased cardiovascular, neurologic, and thromboembolic events. While recent ASGE guidelines recommend that AP/AC should be reinitiated after endoscopy, it is unclear how often endoscopists formally document AP/AC resumption recommendations and the impact on adverse events (AE). To determine the rate of documentation for resumption of AP/AC medication after routine endoscopy and the associated AE risk rate. We retrospectively identified all patients who underwent endoscopy during a five-year period (1/2012-12/2016) at a single academic medical center. Patients were included if they were on AP and/or AC therapy including novel oral anticoagulants. Data was extracted from the Northwestern Enterprise Data Warehouse to include: demographic and provider information, procedures performed, post procedure recommendations (documented in the endoscopy report), and delayed AE. Patients on aspirin (ASA) alone were analyzed separately. Delayed AE after endoscopy were identified by reviewing documentation during patient visits up to 12 months after the endoscopy. A total of 9094 procedures were performed during the study period, in 6165 unique patients taking AP/AC therapy (Table 1). Of these, 67% (n=6052) were performed on patients taking ASA only while 33% (3042) were performed in patients taking an alternative AP/AC agent with or without ASA (Table 1). The majority (92%) of cases were performed using moderate sedation. Immediate procedure-related (AE) were documented in 0.17% (n= 16). Recommendations regarding resumption of AP/AC medications were documented in 11.7 % (n=1066) of all procedures, and in 21.5% (n=2388) of procedures performed in patients taking a non-ASA AC/AP. However, recommendations were made more often after publication of the ASGE guideline in 2015 (OR 1.27, CI 1.01-1.59), in patients undergoing polypectomy (OR 4.29, CI 3.54-5.20) or hemostasis (OR 3.19, CI 2.37-4.28), and when a fellow was present for the procedure (OR 1.72, CI 1.43-2.06) (Table 2). The overall delayed adverse event rate after endoscopy was 16% (n=1423). The majority of AE (81%) occurred in patients without documented AP/AC recommendations. Despite a significant rate of adverse events when antithrombotic medications are withheld, recommendations for resumption of therapy are not frequently documented after endoscopic procedures. Ultimately, the responsibility falls on the endoscopist to ensure this recommendation is communicated clearly to the patient and documented in the medical record. Quality improvement projects with the aim of increasing appropriate documentation are needed.Table 2: Predictors of Documentation for Resumption of AP/AC and Delayed AEView Large Image Figure ViewerDownload Hi-res image Download (PPT)

Antiplatelet therapy for patients undergoing coronary artery bypass surgery.

Considerable variation in the use and duration of antiplatelet medications during the perioperative and postoperative care of patients undergoing coronary artery bypass grafting (CABG) reflects the limited number of studies focused directly on these patients as well as the variation in the results reported. In this review we highlight the incidence and mechanisms of graft closure as well as the evidence in support of antiplatelet therapy that is balanced by the impact of antiplatelet therapy on the risk of bleeding to provide recommendations for the use of this therapy in patients undergoing CABG. Low-dose acetylsalicylic acid (ASA; ≤ 160 mg daily) reduces the incidence of perioperative myocardial infarction, acute renal injury, and mortality without increasing the risk of bleeding and so is recommended both before and after CABG. The use of dual antiplatelet therapy with ASA plus a P2Y12 antagonist adds a greater risk of bleeding. While additional studies are required, we can make the following recommendations: because of increased bleeding and mortality when patients are treated with clopidogrel preoperatively, CABG should be delayed for five days. Because of increased bleeding when patients are treated with ticagrelor preoperatively, CABG should be delayed for three days. Because of increased bleeding when patients are treated with prasugrel preopera-tively, CABG should be delayed for seven days. For patients who had a coronary stent placed preoperatively or had an acute coronary syndrome preoperatively, resumption of therapy with their P2Y12 antagonist postoperatively for 12 months reduces the subsequent incidence of cardiovascular events.

Bone flap salvage in acute surgical site infection after craniotomy for tumor resection.

Craniotomy surgical site infections are an inherent risk and dreaded complication for the elective brain tumor patient. Sequelae can include delays in resumption in adjuvant treatments for multiple surgeries if staged cranioplasty is pursued. Here, the authors review their experience in operative debridement of surgical site infections with single-stage reimplantation of the salvaged craniotomy bone flap. A prospectively maintained database of a single surgeon's neuro-oncology patients from 2009 to 2017 (JRF) was queried to identify 11 patients with surgical site infection after craniotomy for tumor resection. All patients underwent a protocol of aggressive operative debridement including drilling the bone edges and intraoperative flap sterilization with single-stage reimplantation, followed by tailored-antibiotic therapy. Ten of the 11 patients with frankly contaminated bone flaps from surgical site infection were able to be salvaged in a single-stage procedure. Five of these patients underwent adjuvant chemotherapy and/or radiation without secondary complication. There was one treatment failure in a delayed fashion which required additional surgery for craniectomy; however, this occurred after adjuvant treatment was administered. Surgical debridement and bone flap salvage is safe and cost-effective in managing acute surgical site infections after craniotomy for tumors. Additionally, this practice is likely beneficial in expediting the resumption of cancer therapy.

Clinical efficacy of combined 125I brachytherapy and intermittent androgen deprivation for locally mediate-high risk prostate cancer

Objective To evaluate the clinical efficacy of combined 125I brachytherapy and intermittent androgen deprivation for locally mediate-high risk prostate cancer. Methods A total of 25 patients with prostate cancer ranging from 64 to 85 years old (average age of 75) were recruited. The PSA level of these patients was 10.3~354.8 ng/mL, and the Gleason score was 7~9. All patients were clinically staged as T2~T3N0M0. Under continual epidural anesthesia in the lithotomy position, these patients underwent transrectal ultrasound scans from the basement of the prostate to the apex. Pictures were transmitted to the computer system to undergo three-dimensional reconstruction of the prostate and intra-operational planning. According to the plan, patients received 125I brachytherapy under the guidance of the transrectal ultrasound. All patients underwent maximal androgen blockage (MAB) therapy after surgery. Treatment was stopped when PSA fell to 0 ng/mL and stabilized for 2 months. The criterion for the resumption of hormonal therapy was a continuously increasing PSA level as detected in 3 consecutive tests. Results All 25 patients completed the surgery without complications. The number of implanted seeds was 85~110, with an average of 93. The follow-up period was 8~20 months, with an average of 12 months. One case was diagnosed with bone metastasis 10 months after the surgery. Within the 3 to 6 months after surgery, all the PSA levels fell below the normal level. Ten cases did not reach 0 ng/mL, so they continued the hormonal therapy. Five cases had increasing PSA levels 5~16 months after surgery, so MAB was restarted. After that, the PSA levels decreased to 0 ng/mL within 3~6 months. Two cases changed into hormone independent prostate cancer and bone metastasis occurred in these patients. At the end of the follow up period, the remaining 17 patients' PSA level was 0~1.2 ng/mL, and 10 patients of them had a PSA level less than 0.2 ng/mL. Early complications included mild to moderate urethral irritation (24%, 6/25), acute urine retention (8%, 2/25) and rectal irritation or bloody stool (16%, 4/25). Conclusions The combination of intermittent androgen deprivation and 125I brachytherapy is an effective and safe treatment for locally advanced prostate cancer. Key words: Prostatic Neoplasms; Iodine

Clinical Significance of Interferon-γ Neutralizing Autoantibodies Against Disseminated Nontuberculous Mycobacterial Disease.

Interferon-γ neutralizing autoantibodies (nIFNγ-autoAbs) are reported in patients with disseminated nontuberculous mycobacteria (NTM) infection and may function by increasing the infection risk. Notwithstanding, the prevalence of nIFNγ-autoAbs as well as the clinical presentation, diagnosis, and natural history of disseminated NTM infection in these patients is poorly understood. In this retrospective observational study, data and sera for 331 Japanese subjects with mycobacterial infection were collected and analyzed. IFNγ-autoAb titers in sera were quantified using an enzyme-linked immunosorbent assay; neutralizing capacity was evaluated via flow cytometry. Disseminated NTM was identified in 50 human immunodeficiency virus-uninfected patients. Of these, 30 of 37 (81%) immunocompetent patients had an increased nIFNγ-autoAb titer whereas only 1 of 13 (7.7%) immunodeficient patients had an increased nIFNγ-autoAb titer (P < .0001, χ2 test). Presenting symptoms were nonspecific and NTM infection was not included in the differential diagnosis in most cases. All patients with disseminated NTM and an increased serum nIFNγ-autoAb level received prolonged antimicrobial therapy. In 6 cases when antibiotic treatment was discontinued, NTM infection recurred and required resumption of antibiotic therapy for infection control. The mortality rate was 3.2% in disseminated NTM patients with nIFNγ-autoAbs and 21% in those without. nIFNγ-autoAbs were present in most patients with disseminated NTM infection without a diagnosis of clinical immunodeficiency. Diagnosis of disseminated NTM requires a high degree of suspicion and can be improved by measuring serum nIFNγ-autoAb titer. Long-term antibiotic therapy helps prevent recrudescent NTM infection.

Blood pressure after blinded, randomized withdrawal, and resumption of baroreceptor-activating therapy.

Baroreceptor-activating therapy (BAT) has been shown to control resistant hypertension in one sham-controlled and further observational studies. Incremental but significant reincrease of blood pressure (BP) have been described after open-label temporary withdrawal of such therapy. Our study in 16 randomized patients investigated the course of automated office, ambulatory, and home BP in a randomized, controlled cross-over design. After 4 weeks of blinded and randomized withdrawal in hypertension-controlled long-term carriers of BAT (2.67 ± 1.3 years, 145/104 mmHg), the primary end point of 35 mmHg difference, similar to initial BP drop after BAT initiation, was not reached in any patient. Ambulatory BP rose significantly during BAT off by 10/8 ± 4/3 mmHg (3.13/2.10, P = 0.007/0.002) and automated office BP by 10/4 ± 2/1 (4.17/0.58, P = 0.005/0.03) at 4 weeks after BAT on while mean home BP did not change significantly by 2/2 ± 3/2 mmHg (-5.9/-3.5, P = 0.6/0.5). Our data in a limited study population show, that BP rise after temporary BAT withdrawal is significant but does not reach a magnitude comparable with the initial drop after de novo implantation. Such results points to preserved hypertension control after electrical BAT withdrawal and deserves further pathophysiological and clinical clarification.

Antithrombotic Treatment Management in Patients with Intracerebral Hemorrhage: Reversal and Restart.

Intracerebral hemorrhage is the pathological accumulation of blood within the brain. It is a type of stroke more likely to be lethal or to severely disable the patient and results from a wide variety of causes. On the other hand antithrombotic therapy is used for the prevention or/and the therapy of thromboembolic episodes. Antithrombotic drugs are very effective in reducing risk or mortality rate after a thromboembolic event, yet they are associated with significant hemorrhages. The aim of this article is to review current literature for intracerebral hemorrhage and antithrombotic therapy and offer recommendations on the reversal, the discontinuation and the resumption of antithrombotic therapy. Current literature has been reviewed for intracerebral hemorrhage associated with three major categories of patients, those with atrial fibrillation, those with prosthetic mechanical valves and those with venous thromboembolism. Antithrombotic therapy is categorized in antiplatelet agents and anticoagulants. The risk of intracerebral hemorrhage, of a thromboembolic event and of a rebleeding with or without antithrombotic therapy was also reported. Although no one can deny the usefulness of antithrombotic therapy a therapeutic strategy should be developed in order to optimize the clinical decision of stopping, reversing and restarting antithrombotic treatment. This review concludes in strong recommendations, yet a multidisciplinary panel by a stroke physician or neurologist, a cardiologist, a neuroradiologist and a neurosurgeon should evaluate the benefits and the risks for each patient and decide the best therapeutic strategy.

Resumption of Antithrombotic Therapy in LVAD-associated Intracranial Hemorrhages (P2.273)

Resumption of Antithrombotic Therapy in LVAD-associated Intracranial Hemorrhages (P2.273)

Outcomes in elderly patients admitted to the intensive care unit with solid tumors

BackgroundAs the population ages and cancer therapies improve, there is an increased call for elderly cancer patients to be admitted to the intensive care unit (ICU). This study aimed to assess short-term survival and prognostic factors in critically ill patients with solid tumors aged ≥65 years.MethodsWe conducted a retrospective study. The primary endpoint was ICU mortality. Resumption of anticancer therapy in patients who survived the ICU stay and 90-day mortality were secondary endpoints. All patients aged ≥65 years admitted to the ICU of Georges Pompidou Hospital (Paris, France) between 2009 and 2014 were eligible.ResultsOf 2327 eligible elderly patients (EP), 262 (75.0 ± 6.7 years) with solid tumors were analyzed. These patients were extremely critically ill (SAPS 2 61.9 ± 22.5), and 60.3% had metastatic disease. Gastrointestinal, lung and genitourinary cancers were the most common types of tumors. Mechanical ventilation was required in 51.5% of patients, inotropes in 48.1% and dialysis in 12.6%. Most patients (66.7%) were admitted for reasons unrelated to cancer, including sepsis (30.5%), acute respiratory failure (28.2%) and neurological problems (8.0%). ICU mortality in patients with cancer was 33.6 versus 32.6% among patients without cancer (p = 0.75). Among the cancer EP, the 90-day mortality was 51.9% (n = 136). In multivariate analysis, increased SAPS 2 score and primary tumor site were associated with 90-day death, whereas previous anticancer therapies and poor performance status were not. Among survivor patients from ICU with anti-tumoral treatment indication, 77 (52.7%) had resumption of anticancer treatment.ConclusionsElderly solid tumor patients admitted to the ICU had a mortality rate similar to EP without cancer. Prognostic factors for 90-day mortality were more related to severity of clinical status at admission than the presence or stage of cancer, suggesting that early admission of EP with cancer to the ICU is appropriate.