Repeated Doses of Adriamycin May Be Safely Delivered through the Intraosseous Route In Different Bones In Swine

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4344-4344
Author(s):  
Rodrigo Lima ◽  
Lais Navarro ◽  
Fernando Cesani ◽  
Hal K. Hawkins ◽  
Frederick Huang ◽  
...  
Keyword(s):  
Vascular Access ◽  
Research Funding ◽  
Chemotherapeutic Agents ◽  
Histological Evaluation ◽  
High Dose ◽  
Drug Infusion ◽  
Left Tibia ◽  
Versus Group ◽  
Group 2 ◽  
Group 1

Abstract Abstract 4344 Background: Vascular access is critical to the management of patients undergoing chemotherapeutic treatments. Chemotherapy regimens are delivered via long-term vascular access, which are associated with increased rate of infection and vessel damage. The safety of intraosseous (IO) drug delivery of common cardiovascular drugs has been well established and is accepted as the primary alternative to IV access. The safety of multiple rounds of tissue disruptive chemotherapeutic agents via the IO route, however, is unknown. A 2007 study conducted by this group examined single dose administration of Mitomycin, Adriamycin, and CHOP (cyclophosphamide, doxorubicine hydrochloride, Oncovin, and prednisolone) through the IO route. Results suggested that the IO route of infusing chemotherapy agents could be a safe alternative to IV infusion, based on the short-term evaluation of 7 days. But in a 2008 follow-up study of Adriamycin administered through the IO route in the same bone 3 times over a 72-day period, 10 of 14 animals suffered osteomyelitis and/or fractures in the bones used for the infusions. The current study was designed to explore different drug administration regimens designed to prevent these complications. Method: This study consisted of two groups of swine, each receiving three rounds of Adriamycin infusions, in three different limbs spaced 21 days apart. Group 1: (High Dose-High Concentration, n = 6): 60mg/m2 of Adriamycin was delivered into the bone over 15 minutes (concentration 2mg/ml). Group 2: (Low Dose-Low Concentration, n=6): 25mg/m2 of Adriamycin was delivered into the bone over 15 minutes (concentration 0.4 mg/ml). Sedation was induced with Ketamine, Xylazine, and Telazol and maintained with Propofol. An IO needle (EZ IO, Vidacare Corporation, Shavano Park, TX) was aseptically placed into the left humerus (first infusion), or left tibia (second infusion), or right tibia (third infusion). Saline was delivered before (manual syringe flush of 10 ml) and after the IO drug infusion (10ml/min over 5 minutes via syringe pump) in both groups. Radiographic images were obtained before and after every drug infusion and prior to euthanasia. Animals were monitored daily for signs of pain, swelling, or tissue necrosis and treated as needed for the duration of the study. Thirty days after the last drug infusion, animals were anesthetized and euthanized. Bone samples were harvested and sent for histological evaluation. A scoring system, in which changes in morphology were scored on a 0 to 4 scale with 4 representing the most severe changes, was used for the histological evaluation. Result: The clinical complications observed were related to the usual adverse events of the drug, such as diarrhea and vomiting observed during the first week post injection in both groups. There was no clinical, radiological, or histological evidence of osteomyelitis or fracture. Radiological evaluation showed a delay of the healing process and an increase of the osteoblastic activity in the bones previously injected with Adriamycin in both groups. Histological evaluation showed higher scores for blood (p<0.001), scar (p=0.002), and edema (p=0.04) in the left tibia of the animals of Group 1 versus Group 2. There was a higher incidence of normal marrow tissue present in the left tibia of the animals of Group 2 (p=0.04) and a higher incidence of normal bone spicules was found in the right tibia of the animals of Group 2 versus Group 1 (p=0.04). Conclusion: The IO delivery of lower dose and diluted concentrations of Adriamycin was safer and resulted in less tissue abnormality when compared with higher dose/higher concentration. The IO route with rotation of sites for placement of IO needles may be a feasible option for Adriamycin or other vesicant delivery. Disclosures: Lima: Vidacare Corporation: Research Funding. Navarro:Vidacare Corporation: Research Funding. Philbeck:Vidacare Corporation: Employment. Miller:Vidacare Corporation: Employment, Equity Ownership.

scholarly journals Efficacy of Chemotherapy or Chemo-Anti-PD-1 Combination after Unsatisfactory Response of Anti-PD-1 Therapy for Relapsed and Refractory Hodgkin Lymphoma: A Retrospective Series from Lysa Centers

Blood ◽  
2017 ◽  
Vol 130 (Suppl_1) ◽  
pp. 652-652
Author(s):  
Cédric Rossi ◽  
Julia Gilhodes ◽  
Marie Maerevoet ◽  
Charles Herbaux ◽  
Pauline Brice ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Hodgkin Lymphoma ◽  
Research Funding ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Complete Response ◽  
High Rate ◽  
High Dose ◽  
Group 2 ◽  
Group 1

Abstract Introduction: Hodgkin lymphoma (HL) pts who relapse after high-dose therapy (HDT) and autologous stem cell transplantation (ASCT) and brentuximab vedotin (BV) therapy have a poor outcome. For these relapsed and refractory (R/R) HL pts, anti-PD-1 therapy gives a high rate of objective responses. However, the rate of complete response (CR) remains modest and in the updated results of anti-PD-1 therapy clinical trials, about 50% of pts are still without progressive disease after one year of treatment. As anti-PD-1 therapy modifies the anticancer immune response, we hypothesize that anti-PD-1 therapy may increase sensitivity to chemotherapy (CT) given after anti-PD-1 therapy (sequential strategy) or in combination with anti-PD-1 therapy after an unsatisfactory response to immunotherapy (concomitant strategy). We retrospectively analyzed these two clinical situations in 30 R/R HL pts from LYSA centers treated with anti-PD-1 therapy. Methods: We included R/R HL pts from 14 LYSA centers who received anti-PD-1 therapy in the context of clinical trials (N=4) or an authorization for temporary use (ATU) from the French medical drug agency (N=26). Before the anti-PD-1 therapy, pts had received a median of six (range, 2-14) lines of therapy, 69% had HDT+ASCT, 14% had allograft and 93% had been treated with BV. We considered two groups of pts: i. 19 pts (63%) in whom the anti-PD-1 therapy was stopped at the introduction of CT (Group 1); ii. 11 pts (37%) with an unsatisfactory response to anti-PD-1 therapy in whom a combination of CT with immunotherapy was initiated to optimize the response (Group 2). The quality of the response after the introduction of CT was evaluated retrospectively by each treating physicians according to Cheson 2007 or 2014 criteria. We also determined whether new CT treatments after and in combination with anti-PD-1 therapy led to unexpected toxicities and whether new treatment schedules made pts eligible for allograft. Results: At the start of anti-PD-1, the median age of pts was 37 years old (range, 20-75), 24% had Ann Arbor III/IV stages, 34% had B symptoms and 21% had a performance status (PS) of 2-3. Patients received a median of 10 infusions (range, 2-52) of anti-PD-1 therapy with nivolumab (N=26, 87%) or pembrolizumab (N=4, 13%). The best responses achieved during anti-PD-1 therapy were a complete response (CR) for 5 patients, a partial response (PR) for 17 pts, stable disease (SD) for 2 pts and progression for 6 pts. In group 1, 17 pts were in progression, one pt in PR, and another pt in SD at the end of anti-PD-1 therapy alone. In group 1, after anti-PD-1 therapy, the pts were treated with vinblastine (N=3), gemcitabine (N=2) or bendamustine alone (N=3) or in combination with BV (N=4), GVD (N=1), ICE (N=1), DHAP (N=1), escalated BEACOPP (N=1), vinorelbine (N=1), vepeside (N=1) and caelyx (N=1). In group 2, before the combination, the response status was progression for 7 pts and PR for 4 pts. In group 2, to optimize the response to anti-PD-1, pts received vinblastine (N=7), gemcitabine (N=2) and BV (N=2). In the 28 evaluable pts, 11/18 (61%) in group 1 and 9/10 (90%) in group 2 showed an improved response after chemotherapy alone or combination with anti-PD-1 therapy respectively. In group 1, there were 6 CR (32%), 5 PR (26%), 1 SD (5%) and 6 PD (32%) (Figure 1B). In group 2, there were 5 CR (45%), 5 PR (45%) and 1 SD (10%) (Figure 1A). Of note, among the ten pts treated with vinblastine, 4 were in CR, 3 in RP, 1 in SD and 2 in progression. No unexpected toxicity was observed during the CT. Four pts had an allograft after the sequential CT (N=3) and concomitant CT strategy (N=1). Three pts were in CR 274, 279 and 480 days after the allograft and the fourth has not yet been evaluated. Allografts are now scheduled for 6 pts. With a median follow-up of 9.1 months (95%CI, 6.1-14) following the initiation of chemotherapy (alone or combined) the median PFS and OS were 8.4 and 14.6 months, respectively. Conclusions: Our retrospective study showed that pts with an unsatisfactory response or PD with anti-PD-1 therapy had a new objective response with CT alone (61%) or CT in combination with anti-PD-1 therapy (90%). This response could make some pts eligible for allograft. Prospective clinical trials are needed to confirm the synergistic effect of CT with anti-PD-1 therapy and to determine which CT provides the best results in combination with these checkpoint inhibitors. Figure 1 Figure 1. Disclosures Ysebaert: Janssen: Consultancy, Research Funding, Speakers Bureau. Ghesquières: Celgene and Mundipharma: Consultancy, Honoraria; Roche: Research Funding.

scholarly journals A Prospective Phase II Trial of Lenalidomide and Dexamethasone ( LEN-DEX) in POEMS Syndrome

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 36-36 ◽  
Author(s):  
Arnaud Jaccard ◽  
Anne Lazareth ◽  
Lionel Karlin ◽  
Sylvain Choquet ◽  
Laurent Frenzel ◽  
...  
Keyword(s):  
Research Funding ◽  
Plasma Cells ◽  
Bone Marrow Involvement ◽  
Poems Syndrome ◽  
High Dose ◽  
Neurological Improvement ◽  
Engraftment Syndrome ◽  
Prospective Phase ◽  
Group 2 ◽  
Group 1

Abstract Background. POEMS syndrome is a rare form of B cell dyscrasia combining a proliferation usually of plasma cells, a polyneuropathy, osteocondensing bone lesions and multiple other clinical signs. The pathogenesis is not well understood but VEGF plays a major role. In patients with one or two sclerotic plasmacytoma and no bone marrow involvement, first line therapy should include radiation. For patients with diffuse sclerotic lesions, bone marrow involvement or absence of any bone lesion and for those who have not demonstrated stabilization of their disease 3 to 6 months after completing radiation systemic therapy is indicated, the most effective being high dose chemotherapy with autologous stem cell transplant (ASCT). Radiation of a single lesion is effective in about every other case and is accompanied by a fairly slow improvement of the neurological symptoms, often after initial worsening. ASCT seems to be accompanied by a number of important complications, in particular engraftment syndrome. Outside these 2 treatments there is no consensus therapy. Lenalidomide (LEN), a drug without serious neurological toxicity, has the advantage of being both anti-angiogenic and cytotoxic to malignant plasma cells (Richardson PG, Blood 2002;100(9):3063-7). We have recently reported a series of 20 French patients with POEMS syndrome treated by LEN with a good efficacy. We now report the first 27 patients of a prospective phase II trial using LEN + dexamethasone (LEN-DEX), 2 cycles preceding radiation or high dose treatment trying to obtain a rapid clinical response and to avoid engraftment syndrome or 9 cycles followed by 1 year LENalone in patients who cannot receive radiation or ASCT. Methods. Newly diagnosed or relapsing patients with POEMS syndrome who needed to be treated were eligible. Patients who can be treated by local radiation or intensive treatment with stem cell support receive two 28 day cycles of LEN 25 mg PO Days 1-21 and DEX 40 mg PO Days 1,8,15,22 before radiation or intensive treatment (Group 1), the other patients receive 9 cycles of the same LEN-DEX (Group 2) and then 12 cycles of continuous low dose LEN (10 mg). LEN dose was tapered to 10 mg for patients with a creatinine clearance between 30 and 50 ml/min and DEX to 20 mg for patients above 75 years of age and for those who were frail patients. Main eligibility criteria included a diagnosis of POEMS syndrome according to criteria by Dispenzieri et al (Am J Hematol 2012;87(8):804-14), an age of 18 or more, a creatinine clearance above 30 ml/min, no prior treatment with or contraindication to LEN and no uncontrolled thrombosis. Serum and plasma VEGF, serum electrophoresis, immunofixation and free light chain measurements were centrally monitored. Neurologic evaluations were performed using the Overall Neuropathy Limitations Scale (ONLS), the Neurological Impairment Scale (NIS) and the 10 meter walk test (10MWT). The primary endpoint was evaluation of the effectiveness of LEN-DEX combination using biological responses (decrease of monoclonal protein and serum VEGF level) and secondary endpoints were clinical and particularly neurological responses. Results. Twenty-seven patients have been included in 12 centres, median age was 61 (range 32-75), the median follow-up was 6.6 months (range 2-24). Eighteen patients were in group 1, with radiotherapy in 10 patients and ASCT in 8 patients; 9 patients were in group 2. Nineteen patients were in first line and 8 already treated. Only 2 patients experienced grade 3-4 adverse events due to LEN (cytopenia) and 2 patients had allergic rashes, no thrombotic event occurred. No engraftment syndrome was noted in the 5 patients already treated with ASCT. To date, no patient have died. Evolution of VEGF median values in serum and plasma, M-spike and dFLC levels and evolution of neurological measurements are reported in table 1. Neurological improvement was very rapid in some patients, using ONLS and 10MWT 11/18 evaluable patients had a neurological improvement after 2 cycles with an improvement of 1 or more of the ONLS score and/or change of 0.1 m/s or more in the 10MWT. Only one patient who progressed after nine cycles received another therapy. Conclusion. This is the first prospective trial of LEN-DEX in POEMS syndrome. This combination seems well tolerated in this disease with a good efficacy on VEGF measurements and rapid neurological improvement in the majority of patients. Updated data will be presented at the meeting. Figure 1 Figure 1. Disclosures Jaccard: Celgene: Drug supply to Trial Other. Tournilhac:mundipharma: Honoraria, Other, Research Funding; GSK: Honoraria, Other, Research Funding; Roche: Honoraria, Other, Research Funding. Moreau:celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees.

scholarly journals Treatment Practices and Outcomes in Older Adults with Relapsed/Refractory Diffuse Large B-Cell Lymphoma Treated in the Veterans Health Administration

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4205-4205 ◽  
Author(s):  
Ahmad S Halwani ◽  
Kelli M Rasmussen ◽  
Vikas Patil ◽  
Catherine Li ◽  
Christina Young ◽  
...  
Keyword(s):  
Older Patients ◽  
Research Funding ◽  
High Dose ◽  
High Dose Therapy ◽  
Employment Equity ◽  
Treatment Practices ◽  
Dose Therapy ◽  
Equity Ownership ◽  
Group 2 ◽  
Group 1

Abstract Background: Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive Non-Hodgkin lymphoma, with approximately one third of patients not responding (or relapsing) after receiving first-line (1L) therapy, typically a multi-agent chemoimmunotherapy regimen containing rituximab and doxorubicin. These patients may be treated with a second-line (2L) chemotherapy (CT) or chemoimmunotherapy (CIT) regimen, with the intention to proceed to a high-dose therapy followed by an autologous stem cell transplant (SCT). Unfortunately, a significant proportion of older patients are unable to tolerate such treatment. There is little data on treatment practices and outcomes in older DLBCL patients receiving 2L CT or CIT after failure of 1L therapy. Using electronic healthcare record data from the largest integrated health system in the United States, the Veterans Health Administration (VHA), we examined real-world outcomes of DLBCL patients ≥ 65 years of age receiving 2L CT or CIT following 1L therapy with rituximab and doxorubicin containing regimens. Methods: DLBCL patients diagnosed from 2001-2015 and treated at the VHA were identified by linking information from the VA Clinical Registry System (VACRS) in the VHA Corporate Data Warehouse (CDW) to administrative, laboratory and pharmacy data, and clinical notes in the CDW. Patients were included in the analysis if they: had no evidence of a prior malignancy, were diagnosed with DLBCL, received 1L therapy containing rituximab and doxorubicin for ≥ 21 days, then subsequently received a 2L CT or CIT, and were ≥ 65 years of age at time of 2L treatment. Patient age, gender, race/ethnicity; stage at diagnosis, lactate dehydrogenase (LDH), and Charlson Comorbidity Index (CCI) were extracted from VACRS and/or CDW. Patients were censored at end of study observation period (Dec 31, 2016) or if a second cancer diagnosis occurred following their DLBCL diagnosis. Patients were divided into 2 groups: Group 1 included patients receiving a 2L regimen that, per the National Comprehensive Cancer Network (NCCN) guidelines, is typically used with intention to proceed to high-dose therapy; Group 2 included patients receiving a regimen that, per NCCN, is used in non-candidates for high-dose therapy. Receipt of SCT was identified using ICD codes and/or clinical notes. Results: 230 DLBCL patients met our inclusion criteria. Of these, 223 (97%) were male and 171 (74%) were of non-Hispanic, white ethnicity. Baseline characteristics (at time of 1L) were as follows: 156 (68%) had stage III-IV disease, 154 (67%) had LDH > ULN, and median CCI was 4 (IQR:2-5). The majority of patients (217, 94%) received RCHOP as 1L, with the remaining receiving RCHOP + etoposide (13, 6%). Two thirds of patients, (151, 66%) started 2L within 1 year of starting 1L with a median of 10.6 months between start of 1L and start of 2L. Patients were almost equally divided between the two groups, with Group 1 (109, 47%) and Group 2 (121, 53%). Of the 109 Group 1 patients, 68 (62%) received ifosfamide, carboplatin, etoposide (ICE) +/- rituximab (R), and 22 (20%) received etoposide, methylprednisolone, cytarabine, cisplatin (ESHAP) +/- R. Of the 109 Group 1 patients, 14 (13%) proceeded to SCT within VHA (SCT outside VHA was not extracted for this study). The remaining 121 Group 2 patients received 2L therapy with the following: bendamustine (B) +/- R (28, 23%), gemcitabine, oxaliplatin (Gem-Ox) +/- R (21, 17%), cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) +/- R (17, 14%), cyclophosphamide, etoposide, vincristine, prednisone (CEOP) +/- R (14, 12%), cyclophosphamide, etoposide, prednisone, procarbazine (CEPP) +/- R (12, 10%); CHOP + etoposide +/- R (6%), lenalidomide +/- R (6%). Fewer than 10 of these patients proceeded to SCT. The median OS of all patients was 8 months. Conclusions: This is the first study that details treatment practices and outcomes in a nationwide cohort of older adult patients (≥ 65 years old) with relapsed/refractory DLBCL. Approximately half of these older patients did not receive or were not candidates for regimens typically used with intent for high-dose therapy and autologous transplant. OS for the entire cohort was less than a year. Despite significant advances in available treatments for DLBCL, there remains an unmet need in treatment of relapsed/refractory DLBCL, especially in older patients who have difficulty tolerating high-dose regimens. Disclosures Halwani: Takeda: Research Funding; Seattle Genetics: Research Funding; Pharmacyclics: Research Funding; Miragen: Research Funding; Kyowa Hakko Kirin: Research Funding; Immune Design: Research Funding; Genentech, Inc.: Research Funding; Bristol-Myers Squibb: Research Funding; Amgen: Research Funding; Abbvie: Research Funding. Schulz:Genentech: Employment, Equity Ownership; Roche: Equity Ownership. Li:Roche: Equity Ownership; Genentech: Employment. Masaquel:Genentech: Employment, Equity Ownership; Roche: Equity Ownership. Halloran:Genentech, Inc.: Employment, Equity Ownership; Janssen Pharmaceuticals, Inc: Employment, Equity Ownership. Delong-Sieg:Roche: Equity Ownership; Genentech, Inc.: Employment. Sauer:Genentech: Research Funding; Abbvie: Research Funding; Pharmacyclics: Research Funding; COHRDATA: Research Funding; Amgen: Research Funding.

scholarly journals Interventional nephrology and vascular access practice: A perspective from South and Southeast Asia

2021 ◽  
pp. 112972982110113
Author(s):  
Raja Ramachandran ◽  
Vinant Bhargava ◽  
Sanjiv Jasuja ◽  
Maurizio Gallieni ◽  
Vivekanand Jha ◽  
...  
Keyword(s):  
Southeast Asia ◽  
Vascular Access ◽  
Central Catheter ◽  
Middle Income ◽  
Middle Income Countries ◽  
South And Southeast Asia ◽  
Group 2 ◽  
Venous Fistula ◽  
Economic Constraints ◽  
Group 1

South and Southeast Asia is the most populated, heterogeneous part of the world. The Association of Vascular Access and InTerventionAl Renal physicians (AVATAR Foundation), India, gathered trends on epidemiology and Interventional Nephrology (IN) for this region. The countries were divided as upper-middle- and higher-income countries as Group-1 and lower and lower-middle-income countries as Group-2. Forty-three percent and 70% patients in the Group 1 and 2 countries had unplanned hemodialysis (HD) initiation. Among the incident HD patients, the dominant Vascular Access (VA) was non-tunneled central catheter (non-TCC) in 70% of Group 2 and tunneled central catheter (TCC) in 32.5% in Group 1 countries. Arterio-Venous Fistula (AVF) in the incident HD patients was observed in 24.5% and 35% of patients in Group-2 and Group-1, respectively. Eight percent and 68.7% of the prevalent HD patients in Group-2 and Group-1 received HD through an AVF respectively. Nephrologists performing any IN procedure were 90% and 60% in Group-2 and Group 1, respectively. The common procedures performed by nephrologists include renal biopsy (93.3%), peritoneal dialysis (PD) catheter insertion (80%), TCC (66.7%) and non-TCC (100%). Constraints for IN include lack of time (73.3%), lack of back-up (40%), lack of training (73.3%), economic issues (33.3%), medico-legal problems (46.6%), no incentive (20%), other interests (46.6%) and institution not supportive (26%). Routine VA surveillance is performed in 12.5% and 83.3% of Group-2 and Group-1, respectively. To conclude, non-TCC and TCC are the most common vascular access in incident HD patients in Group-2 and Group-1, respectively. Lack of training, back-up support and economic constraints were main constraints for IN growth in Group-2 countries.

Epidural Clonidine or Bupivacaine as the Sole Analgesic Agent during and after Abdominal Surgery 

1999 ◽  
Vol 90 (5) ◽  
pp. 1354-1362 ◽  
Author(s):  
Marc De Kock ◽  
Philippe Gautier ◽  
Athanassia Pavlopoulou ◽  
Marc Jonniaux ◽  
Patricia Lavand'homme
Keyword(s):  
High Dose ◽  
General Anesthetics ◽  
Visual Analogue Pain ◽  
Pain Scores ◽  
Arterial Blood ◽  
Sedation Scores ◽  
Group 3 ◽  
Group 2 ◽  
High Doses ◽  
Group 1

Background The rationale of this study was to compare high-dose epidural clonidine with a more commonly used agent, such as bupivacaine. This was performed to give a more objective idea of the relative analgesic potency of epidural clonidine. Methods Sixty patients undergoing intestinal surgery during propofol anesthesia were studied. At induction, the patients received epidurally a dose of 10 micrograms/kg [corrected] clonidine in 7 ml saline followed by an infusion of 6 micrograms [corrected] x kg(-1) x h(-1) (7 ml/h) (group 1, n = 20), a dose of 7 ml bupivacaine, 0.5%, followed by 7 ml/h bupivacaine, 0.25% (group 2, n = 20), or a dose of 7 ml bupivacaine, 0.25%, followed by 7 ml/h bupivacaine, 0.125% (group 3, n = 20). Intraoperatively, increases in arterial blood pressure or heart rate not responding to propofol (0.5 mg/kg) were treated with intravenous alfentanil (0.05 mg/kg). Additional doses of propofol were given to maintain an adequate bispectral index. The epidural infusions were maintained for 12 h. In cases of subjective visual analogue pain scores up to 5 cm at rest or up to 8 cm during coughing, the patients were given access to a patient-controlled analgesia device. Results During anesthesia, patients in group 1 required less propofol than those in groups 2 and 3 (78 [36-142] mg vs. 229 [184-252] mg and 362 [295-458] mg; P &lt; 0.05) and less alfentanil than patients in group 3 (0 [0-0] mg vs. 11 [6-20] mg; P &lt; 0.05). Analgesia lasted 380 min (range, 180-645 min) in group 1 versus 30 min (range, 25-40 min) in group 2 and 22 min (range, 12.5-42 min) in group 3 (P &lt; 0.05). There was no suggestion of a hemodynamic difference among the three groups except for heart rates that were significantly reduced in patients in group 1. Sedation scores were significantly higher in this group during the first 2 h postoperatively. Conclusion Our results show that high doses of epidural clonidine potentiate general anesthetics and provide more efficient postoperative analgesia than the two bupivacaine dosage regimens investigated.

scholarly journals NIMG-46. RADIOGENOMIC FEATURES PREDICT CLINICALLY RELEVANT GENOME-WIDE ALTERATION SIGNATURES IN GLIOBLASTOMA

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii158-ii158
Author(s):  
Nicholas Nuechterlein ◽  
Beibin Li ◽  
James Fink ◽  
David Haynor ◽  
Eric Holland ◽  
...  
Keyword(s):  
Machine Learning ◽  
Feature Selection ◽  
Molecular Subtypes ◽  
Feature Selection Method ◽  
Selection Method ◽  
Versus Group ◽  
Mri Features ◽  
Genome Wide ◽  
Group 2 ◽  
Group 1

Abstract BACKGROUND Previously, we have shown that combined whole-exome sequencing (WES) and genome-wide somatic copy number alteration (SCNA) information can separate IDH1/2-wildtype glioblastoma into two prognostic molecular subtypes (Group 1 and Group 2) and that these subtypes cannot be distinguished by epigenetic or clinical features. However, the potential for radiographic features to discriminate between these molecular subtypes has not been established. METHODS Radiogenomic features (n=35,400) were extracted from 46 multiparametric, pre-operative magnetic resonance imaging (MRI) of IDH1/2-wildtype glioblastoma patients from The Cancer Imaging Archive, all of whom have corresponding WES and SCNA data in The Cancer Genome Atlas. We developed a novel feature selection method that leverages the structure of extracted radiogenomic MRI features to mitigate the dimensionality challenge posed by the disparity between the number of features and patients in our cohort. Seven traditional machine learning classifiers were trained to distinguish Group 1 versus Group 2 using our feature selection method. Our feature selection was compared to lasso feature selection, recursive feature elimination, and variance thresholding. RESULTS We are able to classify Group 1 versus Group 2 glioblastomas with a cross-validated area under the curve (AUC) score of 0.82 using ridge logistic regression and our proposed feature selection method, which reduces the size of our feature set from 35,400 to 288. An interrogation of the selected features suggests that features describing contours in the T2 abnormality region on the FLAIR MRI modality may best distinguish these two groups from one another. CONCLUSIONS We successfully trained a machine learning model that allows for relevant targeted feature extraction from standard MRI to accurately predict molecularly-defined risk-stratifying IDH1/2-wildtype glioblastoma patient groups. This algorithm may be applied to future prospective studies to assess the utility of MRI as a surrogate for costly prognostic genomic studies.

scholarly journals A tissue-engineered urinary conduit in a porcine urinary diversion model

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Arkadiusz Jundziłł ◽  
Piotr Kwieciński ◽  
Daria Balcerczyk ◽  
Tomasz Kloskowski ◽  
Dariusz Grzanka ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Urinary Diversion ◽  
Porcine Model ◽  
Histological Evaluation ◽  
Metabolic Complications ◽  
Group 3 ◽  
Group 2 ◽  
The Right ◽  
Group 1

AbstractThe use of an ileal segment is a standard method for urinary diversion after radical cystectomy. Unfortunately, utilization of this method can lead to numerous surgical and metabolic complications. This study aimed to assess the tissue-engineered artificial conduit for urinary diversion in a porcine model. Tissue-engineered tubular polypropylene mesh scaffolds were used for the right ureter incontinent urostomy model. Eighteen male pigs were divided into three equal groups: Group 1 (control ureterocutaneostomy), Group 2 (the right ureter-artificial conduit-skin anastomoses), and Group 3 (4 weeks before urostomy reconstruction, the artificial conduit was implanted between abdomen muscles). Follow-up was 6 months. Computed tomography, ultrasound examination, and pyelogram were used to confirm the patency of created diversions. Morphological and histological analyses were used to evaluate the tissue-engineered urinary diversion. All animals survived the experimental procedures and follow-up. The longest average patency was observed in the 3rd Group (15.8 weeks) compared to the 2nd Group (10 weeks) and the 1st Group (5.8 weeks). The implant’s remnants created a retroperitoneal post-inflammation tunnel confirmed by computed tomography and histological evaluation, which constitutes urostomy. The simultaneous urinary diversion using a tissue-engineered scaffold connected directly with the skin is inappropriate for clinical application.

High-dose enoxaparin in the treatment of abdominal angiostrongyliasis in Swiss mice

2017 ◽  
Vol 92 (6) ◽  
pp. 662-667 ◽  
Author(s):  
A.S.S. Sandri ◽  
R. Rodriguez ◽  
M.M. Costa ◽  
S.M. Porto ◽  
D. Schwingel ◽  
...  
Keyword(s):  
Survival Rates ◽  
Mesenteric Arteries ◽  
High Dose ◽  
Control Groups ◽  
Intestinal Infarction ◽  
Intestinal Lesions ◽  
Group 2 ◽  
High Doses ◽  
And Control ◽  
Group 1

AbstractAbdominal angiostrongyliasis (AA) is caused by Angiostrongylus costaricensis, which inhabits mesenteric arteries. There is no drug treatment for AA, and since intestinal infarction due to thrombi is one of the main complications of the disease, the use of anticoagulants may be a treatment option. Thus, we aimed to assess the effect of high doses of enoxaparin on the prevention of ischaemic intestinal lesions and on the survival of mice infected with A. costaricensis. Twenty-four mice were infected with L3 of A. costaricensis and divided equally into two groups: Group 1, control treated with placebo, and Group 2, treated daily with enoxaparin (2.5 mg/kg) for 50 days. All mice were subjected to necropsy and histological analysis. The results from gross and microscopic assessments showed no variation in the prevalence of lesions between the groups. An analysis was also performed among survivors and non-survivors, showing that animals that died often presented lesions, such as granulation tissue in the serosa, and intestinal infarction and adhesion. The mortality rate did not vary between the enoxaparin-treated and control groups. Thus, we showed that high doses of enoxaparin have no protective effect against AA, as the survival rates and lesions of mice did not vary between the treated and control groups. Considering that the use of prophylactic doses was also shown to be ineffective in a previous study, we do not recommend the use of enoxaparin for AA treatment.

scholarly journals FEATURES OF HEMATOLOGICAL INDICES IN PATIENTS WITH IMPAIRED CARDIAC FUNCTION IN UP-TO-DATE CLINICAL PRACTICE

2021 ◽  
Vol 19 (4) ◽  
Author(s):  
V.K. Tashchuk ◽  
R.A. Nesterovska ◽  
V.O. Kalarash
Keyword(s):  
New York ◽  
White Blood Cells ◽  
Heart Association ◽  
Functional Class ◽  
Hematological Indices ◽  
Neutrophil Lymphocyte Ratio ◽  
Versus Group ◽  
Significant Difference ◽  
Group 2 ◽  
Group 1

Purpose – to investigate the distribution of hematological indices in patients withcardiac insufficiency.Material and methods. Data of 26 case histories with diagnosis of IHD have beenanalyzed. Patients with stable angina pectoris of II-III functional class (FC), Diffusecardiosclerosis, complicated in 17 patients with syndromic manifestations of HF II-IIIFC according to New York Heart Association (NYHA), made up group 1, and 9 patientswithout CH -group 2. Of the group 1 surveyed, there were 8 men and 9 women. Ratioindex of leucocytes and erythrocyte sedimentation rate (ESR): L/ESR=L×ESR/100;Neutrophil-lymphocyte ratio index (N/Li); Lymphocyte to monocyte ratio index (Li / Mo);Lymphocyte to eosinophil index (Li/ E) was used among hematological markers.Results. Analyzing the haemogram data, it was found that group 1 patients, unlike group2 patients, had a significantly higher overall white blood cell count (7,96±1,73) × 109and (4,22 ± 0,24) × 109; p<0,05 due to the number of neutrophils (69,41 ± 6,21) % ascompared to group 2 (51,78±1,79)%; p<0,05 as well as a lower level of lymphocyteswas defined in group 1 (22,06±4,07)% versus group 2 (38,55±1,01)%; p<0,05. In genderstudies, men show elevated levels of eosinophils (4,12±0,83)%, as opposed to women(1,56±0,73) %; p<0,05 and lower level of lymphocytes (18,38±1,69)% versus (25,33±2,24)%; p<0,05 and women had a high level of total white blood cells (9,36±0,66) ×109 thanmen (6,36±0,99)×109; p<0,05, in particular lymphocytes. Analysis of hematologicalindices showed that there was a statistically significant difference in determining theN / Li index, which was increased in group 1 patients (3,28±0,78) у.о versus group 2(1,34±0,05) у.о, p<0,05.Conclusion. In gender comparisons, there is an increase in lymphocytes among womencompared to men, so we can assume that women are less susceptible to systemicinflammation. The increase in the N/Li index ratio is due to severe cardiovascularconsequences among patients with coronary heart disease complicated by heart failure.

scholarly journals Effects of Pituitary Surgery and High-Dose Cabergoline Therapy on Metabolic Profile in Patients With Prolactinoma Resistant to Conventional Cabergoline Treatment

2021 ◽  
Vol 12 ◽  
Author(s):  
Rosa Pirchio ◽  
Renata S. Auriemma ◽  
Domenico Solari ◽  
Mauro Arnesi ◽  
Claudia Pivonello ◽  
...  
Keyword(s):  
Medical Therapy ◽  
Metabolic Profile ◽  
Ldl Cholesterol ◽  
Fasting Glucose ◽  
Pituitary Surgery ◽  
High Dose ◽  
Fasting Insulin ◽  
Beneficial Impact ◽  
Group 2 ◽  
Group 1

ObjectiveControl of prolactin excess is associated with the improvement in gluco-insulinemic and lipid profile. The current study aimed at investigating the effects of pituitary surgery and medical therapy with high dose cabergoline (≥2mg/week) on metabolic profile in patients with prolactinoma resistant to cabergoline conventional doses (&lt;2mg/week).DesignThirty-four patients (22 men, 12 women, aged 33.9 ± 12.5 years) with prolactinoma (4 microadenomas and 30 macroadenomas) were included in the present study. Among them 17 (50%) received pituitary surgery (PS, Group1) and 17 (50%) medical therapy with high dose cabergoline (Group 2).MethodsIn the whole patient cohort, anthropometric (weight, BMI) and biochemical (fasting glucose and insulin, triglycerides, total, HDL and LDL-cholesterol, HOMA-IR, HOMA-β and ISI0) parameters were evaluated before and within 12 months after treatment.ResultsIn Group 1, prolactin (p=0.002), total cholesterol (p=0.012), and triglycerides (p=0.030) significantly decreased after pituitary surgery compared to the baseline. Prolactin significantly correlated with fasting glucose (r=0.056, p=0.025). In Group 2, fasting insulin (p=0.033), HOMA-β (p=0.011) and ISI0 (p=0.011) significantly improved compared to baseline. Postoperative cabergoline dose significantly correlated with Δfasting glucose (r=-0.556, p=0.039) and ΔLDL cholesterol (r=- 0.521, p=0.046), and was the best predictor of ΔLDL cholesterol (r2 = 0.59, p=0.002) in Group 1.ConclusionsThe rapid decrease in PRL levels induced by PS might improve lipid metabolism, whereas HD-CAB might exert a beneficial impact on both insulin secretion and peripheral sensitivity, thus inducing a global metabolic improvement.

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