Study For Treatment Of Patients Research Articles

A systematic review of enrolment criteria and treatment efficacy for microvascular angina.

Microvascular angina (MVA) is an important contributor to morbidity and mortality in patients with non-obstructive coronary artery disease. Despite improvements in its recognition and diagnosis, uncertainty remains around the most effective treatment strategy, and more data are needed. We aimed to evaluate the quality of patient selection in treatment studies of MVA and provide a contemporary overview of the evidence base for the treatment of MVA. PubMed, the Cochrane Library and Google Scholar were searched from inception to 4 November 2023 for all treatment studies in patients with angina and non-obstructive coronary artery disease or coronary microvascular dysfunction. Populations with acute coronary syndrome were excluded (PROSPERO: CRD42023383075). Forty-three studies were included. By contemporary definitions of MVA according to the Coronary Vasomotor Disorders International Study Group criteria, 11 (26%) studies enrolled patients with "definitive" MVA, 24 (56%) with "suspected" MVA, and 8 (19%) did not enrol patients who met the diagnostic criteria. A total of 24 unique treatment interventions were investigated. Most studies were observational and single armed (12/24, 50%) or had a single randomised study (9/24, 38%). Ranolazine is the most well-studied intervention drug. Double-blind randomised controlled trials of ranolazine (n=6) have shown inconsistent improvements in Seattle Angina Questionnaire scores and coronary flow reserve with short-term follow-up. Treatment studies of MVA enrolled a heterogeneous population, with only a quarter meeting contemporary diagnostic criteria for definitive MVA. There is a paucity of high quality, randomised data to support any specific treatment intervention. Larger studies with robust selection criteria, blinded patient-reported outcomes, and long-term follow-up are needed.

FRONTIER: FAPi radioligand open-label, phase 1 study to evaluate safety, tolerability and dosimetry of [Lu-177]-PNT6555—A dose escalation study for treatment of patients with select solid tumors.

TPS3161 Background: Fibroblast activation protein alpha (FAP) is a 170 kDa transmembrane glycoprotein expressed during development, active tissue remodeling, and cancer. Overexpression on cancer-associated fibroblasts in the tumor microenvironment, and on some cancer cells of mesenchymal origin, leads to the presence of FAP in > 90% of epithelial tumors, making FAP a compelling anti-cancer target. PNT6555, a potent FAP-targeting compound with rapid clearance from normal tissues and prolonged tumor retention in preclinical models1, is a radioligand consisting of a DOTA chelator (1,4,7,10-tetraazacyclododecane-1,4,7,10- tetraacetic acid) and a FAP-targeting moiety (Bz-D-Ala-boroPro) connected via an aminomethyl linker. The corresponding gallium-68 and lutetium-177 chelates constitute the imaging and therapeutic theranostic pair of PNT6555 under evaluation in this phase I study. Methods: FRONTIER (NCT05432193) is a multicenter, open-label, multi-dose phase I study of PNT6555 in participants with pancreatic ductal adenocarcinoma, esophageal cancer, colorectal cancer, melanoma skin cancer, cholangiocarcinoma, or soft tissue sarcoma solid tumors with FAP over-expression. The primary aim is to evaluate the safety and tolerability of [Lu-177]-PNT6555 in order to determine a recommended phase II dose (RP2D). Dosimetry, pharmacokinetics, and tumor and immune responses will also be assessed for [Lu-177]-PNT6555, as well as safety, tolerability, and diagnostic performance of [Ga-68]-PNT6555 PET/CT. Key eligibility criteria include being refractory to prior treatment with no alternative available therapeutic options, having adequate organ function, and being FAP-positive on [Ga-68]-PNT6555 PET/CT scan, defined as ≥50% of lesions with an SUVmax of ≥1.5x the liver SUVmean. [Ga-68]-PNT6555 will be dosed at 120 - 220 MBq (3.2 - 5.9 mCi), with PET/CT initiated 90 (±30) min later. FAP-positive participants will receive [Lu-177]-PNT6555 once every 6 weeks for up to 6 cycles. Starting at 4 GBq (108 mCi) ±10%, [Lu-177]-PNT6555 may be escalated by 4 GBq, with a maximum planned dose of 12 GBq. De-escalation by 2 GBq may also occur. Dose finding will be guided by the modified toxicity probability interval (mTPI-2) statistical design with a targeted toxicity rate of 30%. The planned total sample size is 30, with targets of 3-12 DLT evaluable patients per dose level. Cohort 1 has been completed without a DLT. Enrollment to cohort 2 began in January 2023. 1. Hallet R, et al. Pre-clinical characterization of the novel fibroblast activation protein (FAP) targeting ligand PNT6555 for the imaging and therapy of cancer. Presented at SNMMI Annual Meeting April 2022; Vancouver, BC, Canada. Clinical trial information: NCT05432193 .

Evaluation of rTMS in patients with poststroke aphasia: a systematic review and focused meta-analysis.

Aphasia-acquired loss of the ability to understand or express language-is a common and debilitating neurological consequence of stroke. Evidence suggests that transcranial magnetic stimulation (TMS) can significantly improve language outcomes in patients with aphasia. Repetitive transcranial magnetic stimulation (rTMS) has been reported to improve naming in chronic stroke patients with nonfluent aphasia since 2005. We conducted a systematic review and meta-analyses of TMS treatment studies in patients with aphasia. Eight electronic databases (PubMed, Medline, Embase, Scopus, ScienceDirect, Cochrane Central Register of Controlled Trials, Journals@Ovid, and clinicaltrials.gov) were searched for articles. Relevant studies were further evaluated, and studies that met inclusion criteria were reviewed. The searches were limited to human studies written in English and published between January 1960 and January 2020. In keeping with the main objective of this review, we included all studies that carried out treatment using rTMS in stroke patients with aphasia, regardless of the trial (or experimental) design of the study. Studies that implemented between-subject or randomized controlled (RCT) design, cross-over trials, and within-subject or pre-post trials were all included. Standard mean difference (SMD) for changes in picture naming accuracy was estimated. The literature search yielded 423 studies. Fifty articles were further evaluated to be included. Eleven met all inclusion criteria and were chosen for review. Eleven eligible studies involving 242 stroke patients were identified in this meta-analysis. Further analyses demonstrated prominent effects for the naming subtest (SMD = 1.26, 95% CI = 0.80 to 1.71, p = 0.01), with heterogeneity (I2 = 69.101%). The meta-analysis continued to show that there was a statistically significant effect of rTMS compared with sham rTMS on the severity of aphasia. None of the patients from the 11 included articles reported adverse effects from rTMS. There are some strong studies evaluating the efficacy of rTMS in stroke patients but further research is required to fully establish the usefulness of this treatment. This meta-analysis indicates a clinically positive effect of rTMS with or without speech and language therapy (SLT) for patients with aphasia following stroke in overall language function and expressive language, including naming, repetition, writing, and comprehension. Low-frequency (1Hz) rTMS over the unaffected hemisphere is effective and compatible with the concept of interhemispheric inhibition. Moreover, the treatment of 1Hz rTMS for patients with aphasia after stroke was safe.

PO-1818 Prospective study of tadalafil treatment in patients treated with prostate brachytherapy in Japan.

PO-1818 Prospective study of tadalafil treatment in patients treated with prostate brachytherapy in Japan.

A meta-analysis of the effects of repetitive transcranial magnetic stimulation on aphasia rehabilitation in stroke patients

Background & Objective: Aphasia—acquired loss of the ability to understand or express language—is a common and debilitating neurological consequence of stroke. Evidence suggests that transcranial magnetic stimulation (TMS) can significantly improve language outcomes in patients with aphasia. Repetitive transcranial magnetic stimulation (rTMS) has been reported to improve naming in chronic stroke patients with nonfluent aphasia since 2005. Methods: We conducted a systematic review and meta-analyses of TMS treatment studies in patients with aphasia. Eight electronic databases (PubMed, Medline, Embase, Scopus, ScienceDirect, Cochrane Central Register of Controlled Trials, Journals@ Ovid, and clinicaltrials.gov) were searched for articles. Relevant studies were further evaluated and studies that met inclusion criteria were reviewed. We included studies if were: randomized controlled blinded clinical trials, meta-analyses or crossover designs of rTMS alone or with speech therapy or any other therapy tested with rTMS. Standard mean difference (SMD) for changes in picture naming accuracy was estimated. Results: The literature search yielded 423 studies. Fifty articles were further evaluated to be included. Eleven met all inclusion criteria and were chosen for review. Eleven eligible studies involving 301 stroke patients were identified in this meta-analysis. Further analyses demonstrated prominent effects for the naming subtest (SMD = 1.26, 95% CI = 0.80 to 1.71, P=0.01), with heterogeneity (I2 = 69.101%). The meta-analysis continued to show that there was a statistically significant effect of rTMS compared with sham rTMS on the severity of aphasia. None of the patients from the 11 included articles reported adverse effects from rTMS. Conclusions: There are some strong studies evaluating the efficacy of rTMS in stroke patients but further research is required to fully establish the usefulness of this treatment. This meta-analysis indicates a clinically positive effect of rTMS with or without speech and language therapy (SLT) for patients with aphasia following stroke in overall language function and expressive language, including naming, repetition, writing, and comprehension. Low-frequency (1 Hz) rTMS over the unaffected hemisphere is effective and compatible with the concept of interhemispheric inhibition. Moreover, the treatment of 1 Hz rTMS for patients with aphasia after stroke was safe.

Abstract 425: Expanded access program of the PLK1 inhibitor onvansertib for treatment of patients with KRAS-mutant metastatic colorectal cancer

Abstract Introduction: Chemotherapy in combination with targeted agents are standard-of-care options for first and second-line treatment of metastatic colorectal cancer (mCRC) patients. Second-line treatment of KRAS-mutated mCRC confers a dismal patient outcome with response rates of 4% to FOLFIRI (5-fluorouracil (5FU), leucovorin, irinotecan) + bevacizumab and median progression-free survival of 5.5 months (Tournigand et al., JCO 2004). PLK1 is a serine/threonine kinase, master regulator of mitosis and its overexpression is associated with poorer outcomes in CRC (Weichert et al., World J. Gastroenterol. 2005). Onvansertib is an oral and highly selective PLK1 inhibitor with demonstrated efficacy as a single agent and synergistically with irinotecan and 5-FU in CRC preclinical models. Onvansertib was granted Fast Track Designation by the Food and Drug Administration for its clinical development program and is currently being investigated in combination with FOLFIRI + bevacizumab in a phase 1b/2 clinical study for second line treatment of patients with KRAS-mutated mCRC (NCT03829410). Preliminary results indicate that onvansertib in combination with chemotherapy is safe and efficacious and that early changes in plasma KRAS mutant are predictive of clinical response (ESMO 2020, Poster #2969). Method: An expanded access program (EAP) was initiated to provide access to onvansertib for treatment of patients who do not meet eligibility criteria for enrollment in the clinical trial, and provides an opportunity to collect safety and efficacy data outside of the clinical study. Patients must be at least 18 years old, have confirmed metastatic and unresectable CRC with a KRAS mutation and have failed or progressed on standard of care systemic therapy. Patients are treated with onvansertib (15 mg/m2, Days 1 to 5 of a 14-day cycle) in combination with FOLFIRI + bevacizumab (Day 1 of each cycle). Patients are being monitored for safety, efficacy by radiographic scans, and for changes in KRAS mutant allelic frequency (MAF) in circulating tumor DNA (ctDNA) by liquid biopsy. Result: The EAP was activated on June 9th 2020. As of November 12th 2020, 19 patients have been treated at 11 clinical sites across the United States. Changes in KRAS MAF after two cycles of therapy was evaluated in 17 patients. Thirteen patients had a KRAS mutation detected in ctDNA at baseline and 8 patients showed a decrease of >50% in KRAS MAF after the first two cycles. Clinical outcomes including efficacy and its correlation with changes in KRAS MAF will be presented at the AACR Annual meeting. Conclusions: The EAP provides a path for patients who may benefit clinically, but are not eligible for the ongoing clinical trial, to gain access to onvansertib treatment. Citation Format: Manish R. Sharma, Daniel Isaac, Ryan Ramaekers, Maya Ridinger, Mark Erlander, Lawrence Mendelsohn. Expanded access program of the PLK1 inhibitor onvansertib for treatment of patients with KRAS-mutant metastatic colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 425.

Identify potent SARS-CoV-2 main protease inhibitors via accelerated free energy perturbation-based virtual screening of existing drugs

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global crisis. There is no therapeutic treatment specific for COVID-19. It is highly desirable to identify potential antiviral agents against SARS-CoV-2 from existing drugs available for other diseases and thus repurpose them for treatment of COVID-19. In general, a drug repurposing effort for treatment of a new disease, such as COVID-19, usually starts from a virtual screening of existing drugs, followed by experimental validation, but the actual hit rate is generally rather low with traditional computational methods. Here we report a virtual screening approach with accelerated free energy perturbation-based absolute binding free energy (FEP-ABFE) predictions and its use in identifying drugs targeting SARS-CoV-2 main protease (Mpro). The accurate FEP-ABFE predictions were based on the use of a restraint energy distribution (RED) function, making the practical FEP-ABFE-based virtual screening of the existing drug library possible. As a result, out of 25 drugs predicted, 15 were confirmed as potent inhibitors of SARS-CoV-2 Mpro The most potent one is dipyridamole (inhibitory constant Ki = 0.04 µM) which has shown promising therapeutic effects in subsequently conducted clinical studies for treatment of patients with COVID-19. Additionally, hydroxychloroquine (Ki = 0.36 µM) and chloroquine (Ki = 0.56 µM) were also found to potently inhibit SARS-CoV-2 Mpro We anticipate that the FEP-ABFE prediction-based virtual screening approach will be useful in many other drug repurposing or discovery efforts.

0753 Cataplexy-Free Days in a Phase 3, Placebo-Controlled, Double-Blind, Randomized Withdrawal Study of JZP-258 in Adults With Narcolepsy With Cataplexy

Abstract Introduction Sodium oxybate (SXB) is a standard of care for the treatment of cataplexy and excessive daytime sleepiness in narcolepsy. JZP-258 is an oxybate product candidate with 92% less sodium. This analysis evaluated cataplexy-free days/week, as a measure of treatment impact, in a placebo-controlled randomized withdrawal study of JZP-258 treatment in patients with narcolepsy. Methods Treatment for cataplexy at study entry included 1) SXB (SXB-only); 2) SXB plus other anticataplectics (SXB+other); 3) anticataplectics other than SXB (other anticataplectics); or 4) cataplexy treatment-naive (anticataplectic-naive). Participants (aged 18-70 years with narcolepsy with cataplexy) began JZP-258 treatment during a 12-week, open-label, optimized treatment and titration period (OLOTTP), followed by a 2-week stable-dose period (SDP). Participants were randomized to receive placebo or continue JZP-258 treatment during a 2-week, double-blind, randomized withdrawal period (DBRWP). Results Of 201 enrolled participants, 134 comprised the efficacy population (placebo, n=65; JZP-258, n=69). Median (Q1, Q3) cataplexy-free days/week at first week of OLOTTP (while initiating JZP-258) by prior treatment were SXB-only, 5.8 (2.0, 7.0); SXB+other, 6.4 (5.0, 7.0); other anticataplectics, 4.0 (1.8, 6.0); anticataplectic-naive, 3.5 (0, 5.8). At end of SDP (on stable dose of JZP-258), median (Q1, Q3) cataplexy-free days/week were 6.0 (3.5, 7.0), 6.1 (1.4, 7.0), 6.0 (2.6, 7.0), and 6.2 (4.0, 7.0), respectively. Prior to randomization, there was no difference in median cataplexy-free days/week between participants to be randomized to placebo (6.0 [3.5, 7.0]) or JZP-258 treatment (6.0 [3.0, 7.0]); during DBRWP, median cataplexy-free days/week decreased in participants randomized to placebo (3.5 [0, 5.83]) but remained similar in participants randomized to continue JZP-258 treatment (5.6 [2.8, 7.0]). The overall safety profile of JZP-258 was similar to SXB. Conclusion Number of cataplexy-free days/week increased with JZP-258 treatment in participants previously naive to oxybate. Number of cataplexy-free days/week decreased during placebo exposure in participants randomized to placebo. Support Jazz Pharmaceuticals

A Study of Secukinumab Treatment in Patients With Plaque Psoriasis and Coexisting Non-alcoholic Fatty Liver Disease (NAFLD)

A Study of Secukinumab Treatment in Patients With Plaque Psoriasis and Coexisting Non-alcoholic Fatty Liver Disease (NAFLD)

Phase 2a Study of NBMI Treatment in Patients With Atypical Parkinsons (PSP or MSA)

Phase 2a Study of NBMI Treatment in Patients With Atypical Parkinsons (PSP or MSA)

Antimicrobial Treatment of Infective Endocarditis, Caused by <i>Enterococcus Faecalis

The frequency of infective endocarditis (IE) has increased 3 times over the past 30 years. The incidence of IE morbidity is recorded in all countries of the world and in the Russian Federation more than 40 people per 1 million population get sick. One of the most frequent causative agents of infective endocarditis is Enterococcus faecalis (E. faecalis), which takes the third place in the structure of the frequency of IE pathogens. Enterococcal IE remains a disease with high mortality, despite the emergence of new groups of antibacterial drugs. This review includes the results of studies of the efficacy and safety of various antimicrobial regimens of IE caused by E. faecalis. The analysis of data from foreign and native studies of antimicrobial treatment in patients with infective endocarditis, accompanied by enterococcal bacteremia is presented in the review. The search for literature performed by using medical databases: MEDLINE, EMBASE, eLIBRARY. The current review included studies of the efficacy and safety of antimicrobial treatment. The main antibiotic therapy regimens of IE caused by E. faecalis include 2 beta-lactam antibiotics or a combination of ampicillin and gentamicin, according to the results of 5 found studies. Found antimicrobial regimens significantly did not affect mortality. Data from international registries testify to the efficacy and safety of daptomycin monotherapy for enterococcal endocarditis. Linezolid and daptomycin are the main drugs of treating infective endocarditis caused by vancomycin-resistant enterococci. Native studies report of a high level of resistance of enterococcal strains to beta-lactam antibacterial drugs. The duration of fever, the frequency of surgical heart valves interventions, the duration of bacteremia are not fully represented in each of the studies, and it is difficult to evaluate these factors. Ampicillin+ceftriaxone and ampicillin+gentamicin are the main antimicrobial treatment regimens of enterococcal endocarditis. Efficacy of these regimens is not significantly different. Treatment of IE should be carried out taking into the epidemiological situation and the strain resistance.

FRI-462-A multicenter international study of sorafenib treatment in patients with hepatocellular carcinoma and chronic kidney disease undergoing hemodialysis

FRI-462-A multicenter international study of sorafenib treatment in patients with hepatocellular carcinoma and chronic kidney disease undergoing hemodialysis

Registry Study of Revcovi Treatment in Patients With ADA-SCID

Registry Study of Revcovi Treatment in Patients With ADA-SCID

LB16. Phase 3 Trial of Baloxavir Marboxil in High-Risk Influenza Patients (CAPSTONE-2 Study)

BackgroundBaloxavir marboxil (BXM), an oral selective cap-dependent endonuclease inhibitor, is effective and safe for treating acute influenza in otherwise healthy patients.MethodWe conducted an international, randomized, double-blind, placebo (PLC)- and oseltamivir (Os)-controlled treatment study in patients at higher risk (HR) of influenza complications. Inclusion criteria included age ≥12 years, fever + influenza symptoms of ≤48 hours duration, and presence of at least 1 HR factor adapted from CDC criteria. Patients were randomized (1:1:1) to a single oral dose of BXM (40/80 mg for BW </≥80 kg), PLC, or 75 mg Os BID for 5 days. The primary endpoint was time to improvement of influenza symptoms (TTIIS) in those with RT-PCR confirmed influenza (ITTI population). Secondary endpoints included infectious virus detection in serial nasopharyngeal swabs, prescription of antibiotics, and influenza-related complications.ResultAmong 2,184 randomized patients, 1,163(53%) comprised the ITTI population (47.9% A/H3N2, 6.9% A/H1N1, 41.6% B). The most common risk factors were asthma or chronic lung disease (39.2%) and age ≥65 years (27.4%). TTIIS was significantly shorter in BXM than PLC (median 73.2 hours vs. 102.3 hours, P < 0.0001) and numerically shorter than Os (81.0 hours, P = 0.8347). TTIIS in BXM patients with A/H3N2 virus (median: 75.4 hours) was significantly shorter than in PLC (100.4 hours; P =0.0141) and was significantly shorter in patients with influenza B (74.6 hours) than in either PLC (100.6 hours; P = 0.0138) or Os (101.6 hours; P = 0.0251). Median time to cessation of viral shedding in BXM patients was 48 hours, significantly less than 96 hours in both PLC and Os patients. Systemic antibiotic use and influenza-related complications were significantly fewer in BXM (3.4% and 2.8%, resp.) than PLC (7.5% and 10.4%; P = 0.0112, and P < 0.0001). The incidence of any (25.1–29.7%) or serious adverse events (0.7–1.2%) did not differ significantly across the groups.ConclusionBXM was well-tolerated and associated with faster recovery and reduced risk of complications in HR influenza patients compared with PLC. It proved superior to Os in shortening the duration of virus replication and in resolving influenza B illness. Oral BXM is a promising treatment option for patients with risk factors for influenza complications.Disclosures M. G. Ison, Romark: Investigator, Research support. Shionogi: Scientific Advisor, Paid DSMB Member. Emergent BioScience: Investigator, Research support. Janssen: Investigator and Scientific Advisor, Consulting fee and Research support. GlaxoSmithKlein: Scientific Advisor, Paid DSMB Member. VirBio: Consultant, Consulting fee. Seqirus: Consultant, Consulting fee. S. Portsmouth, Shionogi Inc.: Employee, Salary. Y. Yoshida, Shionogi & Co., Ltd.: Employee, Salary. T. Shishido, Shionogi & Co., Ltd.: Employee, Salary. F. Hayden, Shionogi & Co., Ltd.: Scientific Advisor, Consulting fee (donated) and travel support for attending 6th ESWI meeting, 10–13 September 2017, Latvia, to present phase 3 OWH results. .T. Uehara, Shionogi & Co., Ltd.: Employee, Salary.

Abstract 3228: Development and characterization of in vitro assays to detect and quantitate tubulysin B hydrazide in biological samples

Abstract EC1456 is a folate-targeted small molecule drug conjugate (SMDC) of tubulysin B hydrazide (TubBH) that is currently in Phase I clinical studies for treatment of patients with folate receptor (FR)-positive tumors. The ability to detect, quantitate, and localize drug in tissues and biological fluids is particularly important for the characterization of its biodistribution and pharmacodynamic properties. To aid in the biological characterization of our targeted TubBH conjugates, our lab had a rabbit polyclonal antibody produced against TubBH for use in various assays. An IgG-purified fraction of antiserum was used to develop competitive ELISA, immunohistochemical, and flow cytometry methods for analysis of biological samples, such as xenograft tumors from animals dosed with drug. Before assay development, a direct ELISA was performed to determine antibody titer and specificity. The TubBH antibody showed excellent binding to immobilized TubBH, whereas a rabbit IgG negative control antibody had minimal binding. Next, a competitive ELISA was developed in which soluble TubBH competed for antibody binding to immobilized antigen. Multiple experimental parameters were optimized, including coating antigen concentration, antibody dilution, and sample matrix extraction method. Using the optimized conditions, the resulting standard curves for TubBH in acetonitrile-extracted KB tumor sample matrix showed good sensitivity and dose-response. It was determined that, in addition to untargeted TubBH, the antibody could also be used to quantitate intact EC1456, as well as a metabolite of the drug lacking the hydrazide. The utility of the antibody was further demonstrated utilizing a PSMA-targeted version of TubBH. Once optimized, the ELISA method was used to analyze FR-positive KB and FR-negative A549 xenograft tumor homogenates from animals dosed with either EC1456 or untargeted TubBH. The levels of TubBH were higher 4h-post EC1456 dose in the FR-positive KB tumors compared to the FR-negative A549 tumors; however, levels were similar after 24h. Moreover, untargeted TubBH resulted in lower tumor concentrations of the drug compared to EC1456 in KB tumors. An immunohistochemical method developed using the antibody showed strong, focal, cytoplasmic staining in FFPE tumor sections of KB tumors from animals dosed with EC1456, while no staining was observed in tumors from undosed animals. Finally, the antibody was successfully used to detect cell surface FR-bound EC1456 on fixed and unfixed KB cells in vitro by flow cytometry. This experiment confirmed that the antibody is able to recognize the conjugate even when it is situated in the FR binding pocket. Collectively, these results show that this antibody against TubBH can be used as a powerful tool for analysis of tumor drug uptake for folate-targeted TubBH in xenograft models and could hold great potential for use in patient sample analysis as well. Citation Format: Nikki L. Parker, Jonathan M. Shillingford, Melissa Nelson, Joseph A. Reddy, Christopher P. Leamon. Development and characterization of in vitro assays to detect and quantitate tubulysin B hydrazide in biological samples [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3228. doi:10.1158/1538-7445.AM2017-3228

Patient subgroups; pooled analysis from the phase 3, PIONEER studies of adalimumab treatment in patients with moderate to severe hidradenitis suppurativa

Patient subgroups; pooled analysis from the phase 3, PIONEER studies of adalimumab treatment in patients with moderate to severe hidradenitis suppurativa

A retrospective study of homoeopathic treatment in patients with heel pain with or without Calcaneal Spur

Background: Heel pain is a common clinical condition which significantly affects the quality of life. It is frequently associated with calcaneal spur (CS). Despite its high prevalence, the optimal treatment remains unclear. The aim and objective of this study is to evaluate the extent of CS in heel pain; correlation of CS with some sociodemographic and health-related factors; and outcome of homoeopathic treatment over a period of 6 months. Methodology: It was a retrospective study done at Dr. Anjali Chatterjee Regional Research Institute for Homoeopathy, Kolkata. Samples were selected from the patients referred for ankle X-ray from August 2014 to July 2015 for nontraumatic heel pain. Their files were traced from outpatient department, and treatment records were reviewed over the next 6 months. Results: Totally 92 patients, 70 women and 22 men, had undergone lateral X-ray of ankle for nontraumatic heel pain, of which 76 (82.6%) patients had CS. Extent of CS was found to be higher in case of females, older age, overweight, and profession of housemaid or manual labor. Homoeopathic treatment showed positive response in nearly 75% of the CS patients. The most useful medicines were Calcarea flouricum, Rhus toxicodendron, Ledum palustre, and Aranea diadema. Conclusion: CS was found in nearly 80% of patients presenting with heel pain, which showed association with female sex, overweight, increasing age, and profession requiring heel stress. Homoeopathic treatment was effective in 3/4th of CS patients, and Rhus toxicodendron and Calcarea flouricum are the two most commonly used medicines.

Results of application of intramedullary telescopic fixators in the treatment of long bone deformities of limbs in children with osteogenesis imperfecta

Various fixators are used today for the correction of the long bones deformities in patients with osteogenesis imperfecta (OI) with giving preference to intramedular telescopic fixators (ITF). But none of them provides rotation stability, which causes ad­ditional immobilization in the postoperative period. In Sytenko Institute of Spine and Joint pathology ITF that meets the prin­ciples of axial and rotation stability has been developed. Ob­jective: to perform a comparative study of surgical treatment in patients with OI using two versions of the ITF. Methods: 9 patients with OI has been studied, who underwent surgical treatment of combined deformation in 30 segments of upper and lower limbs using ITF: humerus — 2 segments (6.7%), femur — 15 (50 %), tibia -13 (43.3 %). Patients were divided into two groups: — 3 children (33.3 %), which had 5 rotation unstable ITF, II — 6 (66.7 %) and 25 patient had rotation stable ITF (83.3 %). Follow-up period ranged from 1 month to 5 years and 2 months. Results: growth segments in length recorded in all pa­tients and was equal to 1.2 to 21.2 mm (thigh), from 1.7 to 9.3 mm (tibia). It was recorded lengthening ITF: femoral segment — from 1.0 to 20.6 mm, tibia — from 1.3 to 9 mm. In group II pa­tients had improved, and in some cases, the restoration of func­tional motor skills and walking (improved support-kinematic function of the lower extremities by 5 classes, and in 3 cases by 7). In 5 patients (55.5 %), which didn't walk preoperative­ly had possibility to vertical standing and walking. We found declined percentage of complications associated with the use of fixators, after the establishment of the ITF rotational stability. Conclusions: The use of ITF provides rotational stability, restores function of limbs and walking, early start of rehabilita­tion, reduced complications rate, self improvement and quality of patients life.

Long-term outcomes of antipsychotic treatment in patients with first-episode schizophrenia: a systematic review.

BackgroundTreatment during first-episode psychosis (FEP) or early schizophrenia may affect the rates of relapse and remission, as well as cognitive functioning, over time. Prolonged duration of psychosis is associated with a poor prognosis, but the effects of treatment in patients with FEP or early schizophrenia on the long-term outcomes are not well defined.ObjectiveTo understand the long-term effects of treatment with antipsychotic agents on remission, relapse, and cognition in patients with FEP or early schizophrenia.MethodsUsing PubMed and Scopus databases, a systematic review was undertaken of articles published between January 1, 2000, and May 20, 2015, that reported randomized and nonrandomized prospective clinical trials on the long-term effects of oral or long-acting injectable antipsychotics on measures of relapse, remission, or cognition in patients with FEP or early schizophrenia. For comparative purposes, trials reporting the effects of later intervention with antipsychotics in patients with longer disease history were also evaluated. Titles, abstracts, and full-text articles were independently screened for eligibility by all the authors based on the predefined criteria.ResultsNineteen studies met inclusion criteria: 13 reported long-term outcomes of relapse, remission, or cognition following antipsychotic treatment in patients with FEP and six reported on patients with a longer disease history. Antipsychotic treatment in patients with FEP produced high rates of remission in the year following treatment initiation, and untreated FEP reduced the odds of later achieving remission. Maintenance therapy was more effective than treatment discontinuation or intermittent/guided discontinuation in preventing relapse. Initiating antipsychotic treatment in patients with FEP also produced sustained cognitive improvement for up to 2 years. Antipsychotic therapy also reduced the risk or rate of relapse in patients with a longer disease history, with outcomes in one study favoring a long-acting injectable formulation over an oral antipsychotic.ConclusionTreatment of patients with FEP is associated with benefits in the long-term outcomes of remission, relapse, and cognition. More long-term studies of treatment in patients with FEP are needed to confirm these findings.

Brain Functional Effects of Psychopharmacological Treatment in Major Depression: a Focus on Neural Circuitry of Affective Processing.

In the last two decades, neuroimaging research has reached a much deeper understanding of the neurobiological underpinnings of major depression (MD) and has converged on functional alterations in limbic and prefrontal neural networks, which are mainly linked to altered emotional processing observed in MD patients. To date, a considerable number of studies have sought to investigate how these neural networks change with pharmacological antidepressant treatment. In the current review, we therefore discuss results from a) pharmacological functional magnetic resonance imaging (fMRI) studies investigating the effects of selective serotonin or noradrenalin reuptake inhibitors on neural activation patterns in relation to emotional processing in healthy individuals, b) treatment studies in patients with unipolar depression assessing changes in neural activation patterns before and after antidepressant pharmacotherapy, and c) predictive neural biomarkers of clinical response in depression. Comparing results from pharmacological fMRI studies in healthy individuals and treatment studies in depressed patients nicely showed parallel findings, mainly for a reduction of limbic activation in response to negative stimuli. A thorough investigation of the empirical findings highlights the importance of the specific paradigm employed in every study which may account for some of the discrepant findings reported in treatment studies in depressed patients.