Baseline PT Research Articles

Incidence, characteristics, and risk factors of hypofibrinogenemia induced by generic tigecycline: a retrospective study.

The objective of this study was to evaluate the incidence, clinical features, and risk factors of generic tigecycline-associated hypofibrinogenemia. A single-center retrospective study was conducted in adult patients treated with generic tigecycline. Clinical data were extracted from the electronic medical records. The endpoint was tigecycline-related hypofibrinogenemia, defined as a condition with no abnormality in fibrinogen before tigecycline application, but developing hypofibrinogenemia upon prescription. The risk factors were determined by logistic regression analysis, and the ROC curve was subsequently established. A total of 240 adults prescribed generic tigecycline from May 1st to November 30th 2023 were included. It was shown that hypofibrinogenemia is a frequent side effect of generic tigecycline, with an adverse reaction rate of 42.9% (103/240). However, the incidence of adverse reactions to generic drugs was lower than in previous studies. The cumulative dose of tigecycline (OR:1.002, 95%CI 1.001-1.002, P < 0.001), baseline FIB (OR:0.995, 95%CI 0.992-0.997, P < 0.001), baseline PT (OR:1.247, 95%CI 1.071-1.452, P = 0.004) and baseline ALB (OR:0.931, 95%CI 0.879-0.986, P = 0.025) were identified as independent prognostic factors of tigecycline-related hypofibrinogenemia. We recommend intensive monitoring of coagulation function in patients exhibiting the aforementioned risk factors for generic tigecycline-associated hypofibrinogenemia to ensure patients safety.

Costs of Surgery in Adult Spinal Deformity: Do Higher Cost Surgeries Lead to Better Outcomes?

This was a retrospective study. To assess the impact of surgical costs on patient-reported outcomes in adult spinal deformity (ASD). With increased focus on delivering cost-effective health care, interventions with high-resource utilization, such as ASD surgery, have received greater scrutiny. ASD patients aged 18 years and older with BL and 2-year data were included. Surgical costs were calculated using the 2021 average Medicare reimbursement by Current Procedural Terminology code. Costs of complications and reoperations were intentionally excluded. Patients were ranked into tertiles by surgical cost: highest surgical costs (HC) and lowest surgical costs (LC). They were propensity score matched to account for differences in baseline age and deformity. Bivariate logistic regressions assessed odds of achieving outcomes. Four hundred twenty-one patients met inclusion (60.7yr, 81.8% female, Charlson Comorbidity Index: 1.6, 27.1kg/m 2 ), 139 LC and 127 HC patients. After propensity score matching, 102 patients remained in each cost group with an average reimbursement of LC: $12,494 versus HC: $29,248. Matched cohorts had similar demographics and baseline health-related quality of life. Matched groups had similar baseline sagittal vertical axis (HC: 59.0 vs. LC: 56.7mm), pelvic incidence and lumbar lordosis (HC: 13.1 vs. LC: 13.4°), and pelvic tilt (HC: 25.3 vs. LC: 22.4°). Rates of complications were not significantly different between the cost groups. Compared with the LC group, by 2 years, HC patients had higher odds of reaching substantial clinical benefit in Oswestry Disability Index [odds ratio (OR): 2.356 (1.220, 4.551), P =0.011], in Scoliosis Research Society-Total [OR: 2.988 (1.515, 5.895), P =0.002], and in Numerical Rating Scale Back [OR: 2.739 (1.105, 6.788), P =0.030]. Similar findings were appreciated for HC patients in the setting of Schwab deformity outcome criteria. Although added cost did not guarantee an ideal outcome, HC patients experienced superior patient-reported outcomes compared with LC patients. Although cost efficiency remains an important priority for health policy, isolating cost reduction may compromise outcomes and add to future costs of reintervention, particularly with more severe baseline deformity. 3.

Association between PT, PT-INR, and in-hospital mortality in critically ill patients with tumors: A retrospective cohort study.

Prothrombin time (PT) and PT-INR are independent predictors of mortality in patients with cancer. The PT and PT-INR of cancer patients are independent predictive variables of mortality. However, whether the PT or PT-INR is related to in-hospital mortality in severely ill patients with tumors remains unknown. This was a case-control study based on a multicenter public database. This study is a secondary analysis of data extracted from 2014 to 2015 from the Electronic Intensive Care Unit Collaborative Research Database. The data relevant to seriously ill patients with tumors were obtained from 208 hospitals spread throughout the USA. This research included a total of 200,859 participants. After the samples were screened for patients with combination malignancies and prolonged PT-INR or PT, the remaining 1745 and 1764 participants, respectively, were included in the final data analysis. The key evaluation methodology was the PT count and PT-INR, and the main outcome was the in-hospital mortality rate. After controlling for confounding variables, we found a curvilinear connection between PT-INR and in-hospital mortality (p < 0.001), and the inflection point was 2.5. When PT-INR was less than 2.5, an increase in PT-INR was positively associated with in-hospital mortality (OR 1.62, 95% CI 1.24 to 2.13), whereas when PT-INR was greater than 2.5, in-hospital mortality was relatively stable and higher than the baseline before the inflection point. Similarly, our study indicated that the PT exhibited a curvilinear connection with in-hospital mortality. On the left side of the inflection point (PT <22), a rise in the PT was positively linked with in-hospital mortality (OR 1.08, 95% CI 1.04 to 1.13, p < 0.001). On the right side of the inflection point, the baseline PT was above 22, and the in-hospital mortality was stable and higher than the PT count in the prior range (OR 1.01, 95% CI 0.97 to 1.04, 0.7056). Our findings revealed that there is a curved rather than a linear link between the PT or PT-INR and in-hospital mortality in critically ill cancer patients. When these two laboratory results are below the inflection point, comprehensive therapy should be employed to reduce the count; when these two laboratory results are above the inflection point, every effort should be made to reduce the numerical value to a value below the inflection point.

Comparison of Outcome of Bleeding with Single and Dual Antiplatelet Therapy in Beating Heart Surgery

Objective: To compare the outcome of Bleeding with Single and Dual Antiplatelet Therapy in Beating Heart Surgery Methodology: A total of 102 cases between 25 to 60 years, of either gender, advised CABG procedure and suitable for beating heart surgery were included in the study. Whereas those with known bleeding diathesis, not suitable candidate for beating heart surgery and with concomitant valvular heart disease were excluded from the study. These cases were enrolled through wards of Cardiothoracic Surgery Department, Shaikh Zayed Hospital, Lahore. Three groups were formed A,B and C. Group-A was assigned to DAPT, Group-B was SAPT (single anti platelet therapy) and Group ”C” was on DAPT that is ASPRIN 75 mg and CLOPIDOGREL 75mg till the time of surgery. Control group A was compared with group B (SAPT) and group C (DAPT) for bleeding risk. The indications of blood products transfusion was assessed by baseline HCT platelet counts, PT and APTT. The CABG was carried out through a full sternotomy incision, under general anesthesia by using routine cardio protective measures and surgical techniques. Operating surgeon decided for on pump or off pump CABG. All patients were assessed and managed in ICU after Coronary artery bypass grafting. Duty doctor and anesthetist decided about transfusion of any allogenic blood product. Transfusion decision was made on the basis of routine laboratory values of APTT, ACT, and INR of PT, as well as on Hb. and HCT levels. Moreover, the need of non-self blood products was predicted. Results: In our study, mean age was calculated as 52.65+7.48 years, 50.32+5.68 years and 48.47+5.96 years respectively, 61.76%(n=21) in Group-A, 52.94%(n=18) in Group-B and 44.12%(n=15) in Group-C were male whereas 38.24%(n=13) in Group-A, 38.24%(n=16) in Group-B and 55.88%(n=19) in Group-C were females, comparison of Perioperative blood loss as 597.29+129.26 in Group-A, 643.18+65.42 in Group-B and 654.70+59.16 in Group-C, p value was 0.02. Conclusion: We concluded that Dual Antiplatelet Therapy have more chances of Peri-Operative bleeding as compare to heparin only or Single Antiplatelet Therapy in Coronary artery bypasses grafting on Beating heart. However, it has advantage of short pre procedure stay, reduced chances of ischemic events, less chance of canula related cellulitis and less chances of HIT. Whereas the cases administered with Heparin alone are having a greater chance of canula related cellulitis, expensive, prolonged pre procedure hospital stay with increased chances of HIT (Heparin induced thrombocytopenia. Keywords: CABG , Perioperative bleeding, Dual Antiplatelet Therapy, Single Antiplatelet Therapy

193. Should our corrective realignments be tailored to different frailty states?

<h3>BACKGROUND CONTEXT</h3> Adult spinal deformity is associated with severe pain and disability. Recent literature has shown that surgical intervention can significantly improve patients' quality of life and lessen disease burden. As many patients requiring spine surgery are elderly and often frail, restoration of alignment targets may differ. The literature is scarce on how different frailty states affect realignment goals. <h3>PURPOSE</h3> Modify the age-adjusted alignment goals using the Frailty Index to optimize outcomes in surgical adult spinal deformity (ASD) patients. <h3>STUDY DESIGN/SETTING</h3> Retrospective cohort study of a prospective multicenter database of ASD patients. <h3>PATIENT SAMPLE</h3> This study included 245 ASD patients. <h3>OUTCOME MEASURES</h3> Complications, HRQLs (SRS-22, ODI, SF-36). <h3>METHODS</h3> Operative ASD patients (scoliosis ≥20°, SVA ≥5cm, PT ≥25°, or TK ≥60°) with available baseline and 2-year radiographic and HRQL data were included. ASD frailty index was used to stratify patients into not frail (NF) and frail (F) categories. Linear regression analysis established normative radiographic thresholds, utilizing previously published age specific US-Normative ODI values (Lafage et al) and the frailty index, based on a cohort of patients with an ideal clinical outcome (no major complications, no PJK, and an SRS-satisfaction of >4). Patients were considered "matched" if 2-year postop alignment was within 1 standard deviation (+1SD overcorrected-1SD undercorrected). <h3>RESULTS</h3> A total of 245 patients included (57±15yrs, 82% female, 26±5.14kg/m2, ASD-FI: 2.9±1.6, CCI: 1.8 ±1.7). Patients had a mean level fused of 11.1±4.4, LOS of 7.7 days±4.4, EBL of 1577 mL, operative time of 377 min, with 63% undergoing an osteotomy. In terms of surgical approach, 69.9% posterior-only, and 29.3% had a combined approach. Primary analyses demonstrated correlation between baseline frailty index, PT, PI-LL, SVA, and ODI, (p<0.05). Linear regression analysis developed age and frailty adjusted alignment threshold. Thresholds for correction were found to increase with age, as previously determined by Lafage et al, as well as, increase with a higher frailty index. Frail patients, corresponding to the same age, were found on average to have a higher alignment threshold than not frail patients in SVA, PI-LL, and PT. Controlling for age, CCI, and baseline deformity, frail patients experienced less overall PJK when undercorrected in PI-LL in the Lafage Schwab age-adjusted parameters (.28[.09-.85], p=.024). Patients who achieved a match in the newly developed age and frailty-adjusted parameters in PI-LL had lower rates of PJF (5% vs 15%, p=.014 with improved HRQLs, and those matched in SVA had improved HRQLs when compared to those who were under- or overcorrected. Matched SVA patients had a shorter LOS. <h3>CONCLUSIONS</h3> Age-adjusted alignment by Lafage et al was the first study to recognize that older age warrants a lower degree of correction, and, the original SRS-Schwab criteria was modified accordingly. Alignment targets accounting for both frailty and age were developed with larger thresholds for increasing frailty. In this study, we found patients who were matched in these age and frailty adjusted thresholds had lower rates of PJF and significantly improved HRQL outcomes. <h3>FDA DEVICE/DRUG STATUS</h3> This abstract does not discuss or include any applicable devices or drugs.

COVID-19-Associated Coagulopathy: Safety and Efficacy of Prophylactic Anticoagulation Therapy in Hospitalized Adults with COVID-19

Background:COVID-19-associated coagulopathy increases mortality in patients with COVID-19 infection. The International Society of Thrombosis and Hemostasis (ISTH) has published a guidance document recommending thromboprophylaxis with low-molecular weight heparin (LMWH) for all hospitalized patients with COVID-19. Despite standard dose LMWH thromboprophylaxis, arterial and venous thrombotic events occur in up to 30-40% of COVID-19 patients admitted to the intensive care unit (ICU). It is not known if patients with coagulopathy from COVID-19 benefit from higher levels of prophylactic anticoagulation therapy. No data exist regarding the comparative safety or efficacy of intermediate dose versus standard prophylactic dose LMWH.Study Design and Methods:This is a multi-center, randomized, open-label study (NCT04360824) comparing standard prophylactic dose enoxaparin (40 mg SC daily if BMI < 30 kg/m2; 30 mg SC twice daily or 40 mg SC twice daily if BMI ≥ 30 kg/m2) versus intermediate-weight adjusted dose enoxaparin (1 mg/kg SC daily if BMI < 30 kg/m2 or 0.5 mg/kg SC twice daily if BMI ≥ 30 kg/m2) in hospitalized patients with laboratory-confirmed SARS-CoV-2 infection who are either admitted to an intensive care unit or have a modified ISTH Overt DIC score ≥ 3.Objectives:The primary endpoint is to compare all-cause 30-day mortality of patients treated with standard prophylactic dose versus intermediate-dose enoxaparin. The secondary endpoints are to determine whether the use of standard prophylactic dose versus intermediate dose enoxaparin impacts major bleeding, arterial thrombosis, venous thrombosis, time to intubation or transfusion of blood products. The exploratory endpoints are to determine the effects of SARS-CoV-2 infection on laboratory coagulation parameters to better understand the mechanism of COVID-19 coagulopathy compared to healthy control subjects; parameters include citrullinated histone H3 (H3Cit), a component of neutrophil extracellular traps. The null hypothesis is that intermediate dose enoxaparin (intervention arm) will have a mortality rate that is not less than standard prophylactic dose enoxaparin (standard of care arm). Assuming a true margin of 20%, a sample size of 82 patients in each arm of the study is required to have 80% power when testing for a difference.Baseline Data:Three centers are currently enrolling patients. As of August 1, 2020, we have enrolled 52 patients (28 males and 24 females) with a median age of 61 years (range 24-80). 51% were Caucasian, 36% Hispanic, and 16% other ethnicities. Median BMI was 31 kg/m2 (range 20-52). Baseline D-Dimer was elevated in 95% of participants with a median of 2.23 mg/mL (range 0.39-40.32). The majority of participants had normal baseline PT, PTT, and platelet levels. All patients had fibrinogen levels over 100 mg/dL with a median of 607 mg/dL. Plasma H3Cit was elevated significantly in patients with COVID-19 (n = 21) vs healthy control subjects (n = 10) (6.48 vs 1.09 ng/mL, P = 0.001).Conclusion:Baseline data for the first 52 patients enrolled confirm the presence of multiple risk factors for thrombosis such as elevated BMI, D dimer, and plasma markers of neutrophil extracellular traps. In contrast to initial reports from China, the prevalence of thrombocytopenia and hypofibrinogenemia was very low in our cohort. Hispanics represented 36% of our study population, compared with 19% of overall COVID-19 infections in the region, suggesting a higher severity of illness in this subpopulation. The enrollment of this trial is ongoing with the addition of sites that have larger African American populations. As safety and efficacy data mature, this study will help clarify the optimum dose of prophylactic enoxaparin to prevent COVID-19 associated coagulopathy.DisclosuresNo relevant conflicts of interest to declare.

The role of anterior and posterior insula in male genital response and in visual attention: an exploratory multimodal fMRI study

Several studies highlighted the role of insula on several functions and in sexual behavior. This exploratory study examines the relationships among genital responses, brain responses, and eye movements, to disentangle the role played by the anterior and posterior insula during different stages of male sexual response and during visual attention to sexual stimuli. In 19 healthy men, fMRI, eye movement, and penile tumescence data were collected during a visual sexual stimulation task. After a whole-brain analysis comparing neutral and sexual clips and confirming a role for the bilateral insulae, we selected two bilateral seed regions in anterior and posterior insula for functional connectivity analysis. Single-ROI-GLMs were run for the FC target regions. Single-ROI-GLMs were performed based on areas to which participants fixate: “Faces”, “Genitals,” and “Background” with the contrast “Genitals > Faces”. Single-ROI-GLMs with baseline, onset, and sustained PT response for the sexual clips were performed. We found stronger effects for the posterior than the anterior insula. In the target regions of the posterior insula, we found three different pathways: the first involved in visual attention, onset of erection, and sustained erection; the second involved only in the onset of erection, and the third limited to sustained erection.

10. Pelvic nonresponders, postoperative cervical malalignment, and proximal junctional kyphosis following treatment of adult spinal deformity: influence of realignment strategies on occurrence

BACKGROUND CONTEXT For surgical adult spinal deformity (ASD) patients, determining optimal restoration of alignment and spinal shape is an active area of research. Complex corrective measures taken are in ASD. Incidence of specific alignment outcomes has yet to be investigated in each of the complex realignment ideals. PURPOSE Assess alignment outcomes (pelvic nonresponse [PNR], PJK, postop cervical deformity [CD]) following ASD-corrective surgery in the context of correction relative to various alignment schemas. STUDY DESIGN/SETTING Retrospective cohort study of prospective ASD database. PATIENT SAMPLE A total of 468 ASD patients. OUTCOME MEASURES PNR, PJK, postop CD. METHODS ASD patients with preop, 6-week postop (6W), and 2-year postop (2Y) radiographic data included. PNR: 10-year mismatch (undercorrection; unimproved) from a patient's age-adjusted PT at 6W and maintained at 2Y. Pelvic responder (PR): PT ±10 match age-adjusted goals. Patients were stratified by incremental additions of corrective alignment schemas: (a) improvement in Schwab SVA, (b) matching age-adjusted PI-LL, (c) match postop “ideal” and “theoretical” Roussouly, (d) improvement in proportionality spinal score at 6W. PNR, PJK, and CD development by 2Y were compared within groups, as well as simultaneous improvement/match of the suggested corrective measures (exclusively). In a subanalysis, patients were stratified by severity of baseline PT, low ( 30°) to determine which alignment schema is necessary to achieve less PNR, PJK and postop CD. RESULTS A total of 468 patients (56.3 yrs, 76.5% F; 25.6% PNR, 40.6% PR) met inclusion criteria. Rates of postop PJK (PNR:49.2% vs PR:59.5%) and CD (18.3% vs 25.8%) were significantly less in the PNR group, p 0.050). Undercorrected age-adjusted PI-LL presented with more PNR (60.1%), whereas overcorrected had increased PJK (68.2%), p CONCLUSIONS Following ASD corrective surgery, 25.6% of patients showed residual pelvic malalignment, qualifying as pelvic nonresponders. Use of complex realignment schemas (SRS-Schwab, age-adjusted, Roussouly shape, GAP) decreased rates of pelvic nonresponse, PJK and postop cervical deformity development. Severe (>30°) baseline pelvic tilt requires particular emphasis of proportionality in addition to other realignment ideals. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.

Sex, dietary salt and AT2R impact sodium transporters along the nephron

BackgroundThe Denton lab has reported that females (F) express 4‐fold more angiotensin type 2 receptor (AT2R) than males (M), that the pressure natriuresis (P‐Nat) is activated at lower blood pressures (BP) in F vs. M wildtype (WT) mice and that this advantage is lost in F AT2R KO (KO) mice. Additionally, 7 day 5% NaCl high salt diet (HS) increased BP in F WT and AT2R‐KO, but not in M mice.AimTest the hypothesis that sexual dimorphism in P‐Nat and response to HS are due to distinct renal Na+ transporter profiles and to AT2R expression.MethodsFVB/N WT mice and AT2R‐KO mice of both sexes (n=6) were fed LS (0.02% NaCl), NS (0.24% NaCl) and HS (5% NaCl) diets. 24 hr urine was collected (day 6); kidneys were quick frozen (day 7), dissected into cortex ‘c’ and medulla ‘m,’ and homogenized for quantitative immunoblotting of: Na+/H+ exchanger 3 (NHE3), Na‐HCO3−cotransporter (NBCe1), claudin 2 (cldn2), Na‐K‐2Cl cotransporter 2 (NKCC2) and phosphorylated form (p), Na,K‐ATPase α1, Na‐Cl cotransporter (NCC, NCCp), cldn7, cotransporter kinases (SPAK and OSR1), epithelial sodium transporter (ENaC) α,β, and γ subunits and cleaved forms (‐cl), and aquaporins (AQP1, AQP2).ResultsComparing KO to WT at baseline, only m‐NKCCp and m‐AQP2 had lower abundance (by 20%) in both KO‐F and KO‐M. During LS, NS, HS diets, both genotypes maintained salt balance and similar body weights within sexes.Proximal tubule (PT)NHE3, cldn2, and NBCe1 were 30% less abundant and AQP1 40% more abundant at baseline in WT‐F and KO‐F vs WT‐M and KO‐M. LS diet paradoxically depressed NHE3 in WT‐M, WT‐F, KO‐M. In HS diet, NHE3 decreased in WT‐M and KO‐M.Loop of HenleNKCC2 and Na,K‐ATPase were 20–30% more abundant at baseline in WT‐F and KO‐F vs WT‐M and WT‐ F. HS decreased m‐NHE3 in WT‐M and KO‐F.Distal tubule (DT)NCC, NCCp, SPAK, SPAKp, OSR1p, and cldn7 were all ~ 50% more abundant in WT‐F and KO‐F vs WT‐M and KO‐M. LS diet increased NCC, NCCp in WT‐M and KO‐F; HS diet depressed NCC, NCCp in WT‐F and KO‐F (25 and 40%), c‐NKCC2 was not altered by LS or HS.Collecting ductα‐ENaC‐cl and γ‐ENaC‐cl were 50% more abundant in WT‐F and KO‐F vs. WT‐M and KO‐M. LS diet increased α‐ENaC‐cl across groups. HS diet decreased α‐ENaC‐cl in WT‐F and KO‐F (40 and 50%), but not in WT‐M or KO‐M. HS diet increased AQP2 abundance across groups and increased m‐Na,K‐ATPase in KO‐M and KO‐F (~25%).Conclusions1) Lower PT and higher DT transporters' abundance in F vs. M is not a function of the higher AT2R in WT‐F vs. M. 2) Overall, the depression of sodium transporters along the nephron (NHE3, NCC, ENaC‐cl) during HS diets is amplified in female KO vs. WT indicating that AT2R expression does not facilitate natriuresis via depression of transporter abundance. 3) The shift in P‐Nat to lower BP in F can be attributed to lower baseline PT transporters' abundance. 4) Since WT‐F have 4‐fold higher AT2R expression than WT‐M, the responses to diet salt observed only in WT‐M and KO‐F (m‐NHE3, NCC and m‐Na,K‐ATPase) may reflect similarly low AT2R levels. 5) Baseline AT2R levels are associated with higher medullary NKCC2 and AQP2 abundance which may impact concentration potential.Support or Funding InformationDK083785This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Coagulation Abnormalities and Hemostatic Surgical Outcomes in 142 Patients with Noonan Syndrome

Background: Noonan syndrome, characterized by dysmorphic facies, webbed neck, short stature, chest deformity, developmental delay and congenital heart defects, occurs as a result of mutations affecting the RAS-MAPK signaling pathway. A wide range of coagulation abnormalities are observed in these patients including: thrombocytopenia, platelet dysfunction and coagulation factor deficiencies. Screening for coagulation defects is recommended in childhood and especially prior to surgical procedures. Data available is limited and the extent of the hemostatic evaluation needed is not clearly defined. We carried out this study to outline the spectrum of coagulation abnormalities seen in patients with Noonan syndrome and their impact on surgical outcomes.Methods: In this retrospective cohort study, the electronic medical record system was queried for patients with Noonan syndrome seen at Mayo Clinic between 2000 and 2016. A detailed chart review was undertaken.Resultsi) Phenotypic correlates: 142 patients (58% male) met our study criteria, median age 21 years (range 14 days to 68 years). The referral specialty for initial evaluation was: cardiology 69 (49%), endocrinology 10 (7%), urology 10 (7%), neurology 8 (6%), pulmonary 6 (4%), orthopedic surgery 3 (2%), gastroenterology 2 (1%), psychiatry 2 (1%) and other specialties 4 (3%). Ten patients (7%) were referred for developmental delay, 13 (9%) for dysmorphism and 4 (3%) after having a family member diagnosed with Noonan syndrome. One patient (1%) presented with hematochezia. Twenty-seven (52%) of the 52 patients screened with genetic testing had a Noonan-associated gene defect. Bleeding was reported by 22 patients (15%) with a median International Society on Thrombosis and Haemostasis Bleeding Assessment Tool (ISTH-BAT) score of 2 (range 1-8). Of those tested, 11/121 (9%) patients had thrombocytopenia (platelets < 150 x 10^9/L). Screening coagulation tests were done in 58 (41%) patients, and included PT/aPTT in 43 (74%) and extended coagulation panels (including platelet function studies) in 15 (26%). Of the 22 patients with history of bleeding, 20 (90%) had screening coagulation testing. Twenty-two (38%) of patients screened had one or more coagulation laboratory abnormality. Ten (66%) patients with clinically suspected platelet dysfunction had normal platelet function analyzer (PFA)-100 testing and normal light transmission aggregometry, while 5 (33%) had decreased platelet aggregation with epinephrine. Four patients (7%) (including 2 siblings) had low vWF levels consistent with type 1 vWD, 9 (16%) had mild clotting factor deficiencies ( FIX- 3, FXII-2 and multiple clotting factors-5) and 4 (7%) had a prolonged baseline PT and/or aPTT without additional coagulation factor assessment (Table 1). Thirteen patients (9%) had both a bleeding phenotype and abnormal coagulation laboratory results.ii) Surgical outcomes: A total of 274 surgical procedures were performed in 89 patients (63%). These included: cardiac 118 (43%), orthopedic 30 (11%), ENT 27 (10%), neurosurgical 26 (10%), abdominal 17 (6%), urologic 17 (6%), gynecologic 12 (4%) thoracic 8 (3%), ophthalmologic 7 (3%), plastic surgery 5 (2%), maxillofacial 4 (1%) and lymph node dissection 3 (1%). Platelets were utilized in 26 procedures (10%), fresh frozen plasma in 19 (7%) and cryoprecipitate in 7 (3%). Two procedures were performed in patients with type 1 vWD using vWF concentrates. Abnormal intra or postoperative bleeding was seen in 5/274 procedures (1.8%) performed in 4 patients. One patient had a known functional platelet disorder, one had normal PT and aPTT and two were not screened for coagulation defects. Bleeding was managed with transfusional supportive care in 3 (60%) surgical cases, while in 2 (40%) cases patients required re-intervention to achieve surgical hemostasis (bleeding from femoral access site and pacemaker pocket hematoma). There was no mortality related to the excess perioperative bleeding.Conclusion: Varying hemostatic abnormalities are seen in patients with Noonan syndrome, ranging from thrombocytopenia to multiple coagulation factor deficiencies. Frank bleeding manifestations however are uncommon and when present are usually mild. Clinical evaluation focused on the bleeding history and basic coagulation screening allows for successful perioperative hemostatic support and good surgical outcomes. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Impacts of High-Protein Oral Nutritional Supplements Among Malnourished Men and Women with Sarcopenia: A Multicenter, Randomized, Double-Blinded, Controlled Trial

BackgroundRecent evidence suggests that nutritional interventions may improve muscle outcomes in malnutrition and sarcopenia. ObjectivesWe evaluated the effects of 2 high-quality oral nutritional supplements (ONS) differing in amount and type of key nutrients in older adult men and women. DesignA multicenter, randomized, double-blinded, controlled clinical trial. ParticipantsMalnourished and sarcopenic men and women, 65 years and older (n = 330). InterventionA 24-week intervention period with 2 energy-rich (330 kcal) ONS treatment groups: Control ONS (CONS, 14 g protein; 147 IU vitamin D3) versus Experimental ONS (EONS, 20 g protein; 499 IU vitamin D3; 1.5 g CaHMB) taken twice daily. Both ONS also contained other vitamins, minerals, and nutrients in varying amounts. MeasurementsIsokinetic peak torque (PT, Nm) leg strength, grip strength (kg), and gait speed (m·s−1) were assessed at baseline and 12 and 24 weeks. Left and right leg muscle mass (LMM, kg) were assessed by dual-energy x-ray absorptiometry (DXA). Muscle quality (MQ) was leg strength expressed relative to the tested LMM (Nm·kg−1). Subgroup analyses were performed: severe sarcopenia (low skeletal mass index, low grip strength [<30 kg men; <20 kg women], low gait speed [<0.8 m·s−1]) and mild-moderate sarcopenia (low skeletal mass index, normal gait speed, or normal grip strength). ResultsBoth ONS groups (EONS and CONS) improved PT, MQ, grip strength, and gait speed from baseline with no treatment differences. Those with severe sarcopenia (44%) exhibited lower baseline PT and MQ, with no differences in strength improvements between treatments. However, participants with mild-moderate sarcopenia exhibited higher baseline PT and MQ, with differences in strength improvements at 12 weeks (EONS > CONS, P = .032) in those with normal grip strength. There were no treatment differences based on sarcopenic severity for either grip strength or gait speed. ConclusionONS improved strength outcomes in malnourished older adults with sarcopenia. In those with mild-moderate sarcopenia, but not severe sarcopenia, consumption of the EONS improved leg muscle strength and quality compared with the standard CONS.

Circuit life versus bleeding risk: the impact of achieved activated partial thromboplastin time versus achieved filtration fraction.

Whilst prolonging hemofilter (circuit) life, heparin increases bleeding risk. The impact of achieved activated partial thromboplastin time (APTT) on circuit life and bleeding risk has not been assessed in a modern critically ill cohort. Lowering filtration fraction may be an alternative means of prolonging circuit life, but is often overlooked in critical care. An observational study of 309 consecutive circuits in a general intensive care unit was conducted using a wide target APTT range. Multilevel modeling was used to predict circuit life and bleeding according to achieved APTT and filtration fraction. Independent predictors of circuit failure (i.e. unplanned ending of treatment) included filtration fraction (P<0.001, HR 1.07 per 1% increase), peak APTT (P<0.001, HR 0.8 per 10 s increase or 0.3 APTR increase) and baseline PT (P=0.014, HR 0.91 for every 50% increase). The only significant predictor of bleeding was peak APTT (P=0.017, OR 1.05 per 10 s increase). Every 10 s APTT increase was associated with a 20% reduction in circuit failure, but a 5% increase in hemorrhage. A 3% reduction in filtration fraction was associated with the same improvement in circuit life as a 10 s increase in APTT. Increasing APTT prolongs circuit life but carries a substantial risk of bleeding even in modern practice. Filtration fraction has a large impact on circuit life in the critically ill: a 3% reduction in filtration fraction, e.g. by increasing blood flow or delivering some of the clearance via dialysis, would be expected to reduce circuit failure as much as a 10 s increase in APTT.

Fine-Tuned Surgical Planning in Adult Spinal Deformity: Determining the Lumbar Lordosis Necessary by Accounting for Both Thoracic Kyphosis and Pelvic Incidence

METHODS: This is a multicenter, prospective study of consecutive ASD patients. Inclusion criteria included: ageO18yr, ASD. Patients were stratified into the following age groups: #45yrs, 46-64, 65-74, $75. Multivariate linear regressions were conducted for baseline PT, PI-LL, and SVA with baseline ODI and age on all patients. Based on previous studies, an ODI of 40 was used as the threshold for disability. Individual patient thresholds were calculated based on their age. The thresholds were averaged across the age groups. RESULTS: 833 patients were included, (396 op, 437 nonop). Patients with only sagittal deformity for the age groups were the following: #45(18.8%), 46-64(19.4%), 65-74(40.1%), $75(50%). Age alone significantly predicted ODI (r250.17,p!0.0001). Regressions for PT (r250.27,p!0.0001), PI-LL (r250.27,p!0.0001, SVA (r250.32, p! 0.0001) including age were all predictive of ODI. Thresholds for the entire cohort were the following: PT521.964.7deg, PI-LL511.667deg, SVA56.762.5cm. Thresholds for the age groups were the following: PT (deg): #45(15.362.3), 46-64(22.661.5), 65-74(26.260.8), $75(29.160.8). PI-LL (deg): #45(1.763.5), 46-64(12.562.2), 65-74(1861.2), $75(22.461.3). SVA (cm):#45 (3.361.2), 46-64 (7.160.8), 65-74 (9.060.4),$75 (10.560.4). CONCLUSIONS: Spinopelvic radiographic thresholds correlated to moderate to severe regional low back disability increase as patients’ age. These results suggest that preoperative surgery planning and patient counseling should consider the patient’s age. Further study of Schwab SRS sagittal modifier correction goals for individual age groups is warranted. FDA DEVICE/DRUG STATUS: This abstract does not discuss or include any applicable devices or drugs.

The effects of tranexamic acid and prothrombin complex concentrate on the coagulopathy of trauma

Bleeding is the most frequent cause of preventable death after severe injury. Our purposes were to study the efficacy of tranexamic acid (TXA) and prothrombin complex concentrate (PCC) on a traumatic coagulopathy with a severe native metabolic acidosis and compare the efficacy of PCC versus fresh frozen plasma (FFP) to reverse a dilutional coagulopathy. In vitro effects of TXA and PCC were assessed with standard laboratory analysis (prothrombin time [PT]/international normalized ratio [INR]) and rotational thromboelastometry in a porcine hemorrhage with ischemia-reperfusion (H/I) model. FFP was used in comparison with PCC. In vitro doses were calculated to be the equivalent of 1-g TXA, 100-mg tissue plasminogen activator, 45-IU/kg PCC, and 4-U FFP. Agents were tested at baseline and then with severe metabolic acidosis after 6 hours of resuscitation. Thirty-one swine were studied. Baseline hematocrit was 24%, pH was 7.56, INR was 1.0, and lactate level was 1.47. Six hours after H/I, the hematocrit was 15.9%, pH was 7.1, INR was 1.7, and lactate level was 10.26. Rotational thromboelastometry revealed that maximum clot firmness at baseline was 71.71 mm and decreased to 0.29 mm with tissue plasminogen activator, representing severe fibrinolysis. Following TXA dosing, the maximum clot firmness was immediately corrected to 69.06 mm. There was no difference (p = 0.48) between TXA function at baseline pH (mean, 7.56) or acidotic pH (mean, 7.11). The mean baseline PT was 13 ± 0.49 seconds (INR, 1). After H/I and resuscitation, the mean PT was 23.03 seconds (INR, 2.1). PCC reduced the PT to 20 (INR, 1.75; p = 0.001) and FFP to 17.44 (INR, 1.47; p = 0.001). Both TXA and PCC seem to function well in reversing a traumatic coagulopathy in vitro, and TXA seems to have no loss of function in a severe metabolic acidosis. Further investigations are warranted.

Role of Terlipressin and Albumin Combination versus Albumin Alone in Hepatorenal Syndrome

Purpose: Hepatorenal Syndrome is potentially fatal complication of decompensated cirrhosis. Major pathogenetic factor is systemic arterial vasodilatation with arterial underfilling and renal vasoconstriction. Vasoconstrictor therapy (terlipressin) is used to increase systemic vasoconstriction. Albumin improves intravascular filling and reduces extent of systemic arterial vasodilatation, thus improving result of Terlipressin. We performed this study to see the impact of both modalities on disease outcome. Methods: Fifty patients hospitalized with HRS, were randomly assigned either terlipressin (1mg/4 hourly, IV), and albumin (1 g/kg followed by 20-40 g/day) (n=25) or albumin alone (n=25) for a period of 7 to 10 days. Inclusion criteria: (1) cirrhosis diagnosed by liver biopsy or clinical, biochemical, ultrasound, or endoscopic findings; (2) HRS either type 1, or type 2 with serum crt > 2mg/dL; (3) age 18 to 75 years; (4) absence of bacterial infection (5) absence of cardiovascular diseases (6) absence organic nephropathy; and (7) absence of HCC. Primary outcomes were improvement of renal function and survival at 3 months. Final analysis was conducted on an intention-to-treat basis. Comparisons between groups were performed with the use of the χ2 test or Fisher exact test and Mann-Whitney/Wilcoxon tests for continuous data. Data was analyzed with SPSS 14.0 software. Results are presented as mean ± SD. P values are 2-tailed, and values <.05 were considered statistically significant. Results: Improvement of renal function was more frequent in patients given Terli+Riba than in patients given albumin alone: 10 out of 25 patients (40%), compared with 2 out of 25 patients (8.0%), (P<.05). Patients of Terli+Alb group, 7 had type 1 HRS, and 3 had type 2 HRS. 2 patients who responded in Alb group had type 1 HRS. Duration of treatment was 10 days ± 2 days. In Terli + Alb group, serum crt decreased from 3.9 ± 0.6 to 1.2 ±0.4 mg/dL (P <.05) and MAP increased from 85 ±12 to 74 ±12 mm Hg (P =.02). There were no significant difference in 2 groups with respect to the number of patients who were alive at 3 months, 6 in the Terli+Alb group (24%) and 5 in the albumin group (20%) (P=.6). A univariate analysis of survival showed that baseline bilirubin, PT, serum crt, CPT score, MELD score and response to therapy were associated with prognosis. In multivariate analysis, predictive factors of 3-month survival were baseline MELD score and therapy response. Conclusion: Results of this study indicate that terlipressin and albumin are effective in improving renal function in patients with cirrhosis and HRS compared with albumin administration alone. However, there is no significant effect of Terli+Riba therapy on survival.

Decitabine Is Effective In Patients with Myelodysplastic Syndromes Who Failed Prior Intensive Regimen: No Negative Impact of Prior Therapy

AbstractAbstract 2936 Background:Decitabine is a hypomethylating agent (HMA) with demonstrated activity and an acceptable safety profile for the treatment of all FAB subtypes of myelodysplastic syndromes (MDS). A retrospective analysis was conducted to determine the effect of prior MDS treatment on overall response rate (ORR), duration of response, time to response, and overall survival (OS). Methods:Of 188 patients, 54 had prior MDS treatment consisting of cytotoxic chemotherapy (n=31), immunomodulators (n=21), stem cell transplant (n=4), monoclonal antibodies (n=2), oblimersen (n=1), or HMAs (n=1) were identified from two clinical trials with decitabine (Phase III, 3-day and Phase II, 5-day dosing studies). Patients were stratified on the basis of those who had received prior treatment (PT, n=54) for MDS and those who had not (NPT, n=134). Descriptive statistics were used to quantify the differences between the two groups for baseline characteristics, response rates (based on IWG 2006 criteria), safety and survival data. Results:Baseline characteristics showed the PT group had a longer time from diagnosis; the NPT group had a greater percentage of patients with High risk and Int-2 IPSS scores. There were differences noted in the baseline NPT group (5-day dosing only), with more patients with FAB classification of RAEB and RAEB-t (n=45), whereas the baseline PT group had a greater number of CMML patients (n=8). Objective response rate (ORR), overall improvement rate (OIR) and median survival were greater in NPT patients with no significant difference observed between the groups (Table 1). Patients with PT had a shorter duration of improvement (median 208 days) vs. the NPT group (median 296 days, p=NS) for the 5-day dosing study. Conclusions:Decitabine is active in patients with MDS with low rate of side effects. Prior therapy with intensive regimens have no impact on response to decitabine and such patients should be considered for hypomethylating therapy.DACO-007 Study (N=89)DACO-020 Study (N=99)PT (n=27)NPT(n=72)Chi SquarePT(n=)NPT(n=)Chi SquareORR, % (CR+PR)11.1(n=3)19.3(n=12)NS25.9(n=7)36.1(n=26)NSORI, % (CR+PR+HI)22.2(n=6)32.3(n=20)NS44.4(n=12)54.2(n=39)NSMedian OS, days (95% CI)334(183–583)462(319–513)NS548(184–802)582(447–760)NS Disclosures:Jabbour:Eisai Inc.: Editorial and statistical support, Honoraria. Kantarjian:Novartis: Research Funding; Pfizer: Research Funding; Bristol Myers Squibb: Research Funding; Novartis: Consultancy. Borthakur:Eisai Inc.: Research Funding. Cortes:Novartis: Research Funding; Pfizer: Consultancy, Research Funding; Bristol Myers Squibb: Research Funding. Ravandi:Eisai Inc.: Research Funding; Eisai Inc.: Honoraria.

Carprofen and buprenorphine prevent hyperalgesia in a model of inflammatory pain in cats

A model of nociceptive threshold determination was developed for evaluation of NSAID analgesia in cats. In a crossover study, eight cats received carprofen (4 mg/kg), buprenorphine (0.01 mg/kg) or saline (0.3 ml) subcutaneously before intradermal kaolin injection on the antebrachium to induce mild inflammation. Pressure thresholds were measured at the injected site using blunt-ended pins advanced by manual inflation of a bladder within a bracelet. Bladder pressure was recorded as threshold (PT) at the behavioural end point. Baseline PT were recorded before kaolin injection (time 0). PT was measured at 2–10 h intervals for 52 h. PT below the lower 95% confidence interval (CI) of baseline values indicated hyperalgesia. After saline, hyperalgesia was detected from 2–6 h, 22–26 h, and at 30 and 36 h. After carprofen, PT remained within the 95% CI. After buprenorphine, PT remained within the 95% CI except at 2 h. Carprofen and to some extent buprenorphine, prevented inflammatory hyperalgesia.

The Effects of Perioperatively Administered Colloids and Crystalloids on Primary Platelet-Mediated Hemostasis and Clot Formation

The Effects of Perioperatively Administered Colloids and Crystalloids on Primary Platelet-Mediated Hemostasis and Clot Formation