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1. Loss of Y in regulatory T lymphocytes in the tumor micro-environment of primary colorectal cancers and liver metastases

Author

Wójcik, Magdalena, Juhas, Ulana, Mohammadi, Elyas, Mattisson, Jonas, Drężek-Chyła, Kinga, Rychlicka-Buniowska, Edyta, Bruhn-Olszewska, Bożena, Davies, Hanna, Chojnowska, Katarzyna, Olszewski, Paweł, Bieńkowski, Michał, Jankowski, Michał, Rostkowska, Olga, Hellmann, Andrzej, Pęksa, Rafał, Kowalski, Jacek, Zdrenka, Marek, Kobiela, Jarek, Zegarski, Wojciech, Biernat, Wojciech, Szylberg, Łukasz, Remiszewski, Piotr, Mieczkowski, Jakub, Filipowicz, Natalia, and Dumanski, Jan P.

Published
2024
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2. Angiogenic activity of sera from interstitial lung disease patients in relation to clinical and radiological changes

Author

Zielonka TM, Demkow U, Zycinska K, Filewska M, Bialas B, Kus J, Radzikowska E, Remiszewski P, Szopinski J, Soszka A, Wardyn KA, and Skopinska-Rozewska E

Subjects
angiogenesis, interstitial lung diseases, clinical symptoms, radiological changes, Medicine
Abstract

Abstract Objective Clinical symptoms and radiological changes are useful in monitoring patients with interstitial lung diseases (ILD). Neovascularization participates in the pathogenesis of idiopathic pulmonary fibrosis and other ILD. The objective of the study was to examine the relationships between angiogenic activity of sera from ILD patients and clinical or radiological status. Material and methods Serum samples were obtained from 83 patients with sarcoidosis, 31 with idiopathic pulmonary fibrosis (IPF), 29 with hypersensitivity pneumonitis (HP), 16 with collagen diseases with pulmonary manifestation (CD), 13 with scleroderma (SCL), 14 with Wegener's granulomatosis (WG), 12 with pulmonary Langerhans cell histiocytosis (HIS), 12 with pneumoconiosis (PNC), 10 with drug-induced lung disease (DLD), 5 with cryptogenic organizing pneumonia (COP), and from 36 healthy volunteers. As an angiogenic test we used a cutaneous angiogenesis assay according to Sidky and Auerbach. Clinical status was evaluated using a special questionnaire. In all patients chest radiographs were performed. Results The angiogenic properties of sera from ILD differed depending on the clinical diagnosis. The strongest proangiogenic effect was induced by sera from patients with HP (mean number of new vessels 16.8), CD (16.6), sarcoidosis (16.3), IPF (16.2), and PNC (15.7). In the case of DLD (13.2), the effect was comparable to healthy controls (13.5). In contrast, sera from SCL (mean number of the vessels 10.5) and HIS patients (10.8) significantly inhibited angiogenesis compared with controls. The angiogenic activity of sera from patients with hilar or mediastinal lymph nodes involvement was higher than that of sera from patients with lung fibrosis. There were also differences in the serum angiogenic activity in relation to the severity of dyspnea. Conclusions The data showed that sera from ILD patients constitute a source of mediators modulating angiogenesis, but the pattern of reaction is different in various diseases. Sera from HP, sarcoidosis, IPF, and CD patients demonstrated the strongest proangiogenic activity. However, sera from SCL and HIS inhibit angiogenesis. Angiogenic activity of examined sera was related to the clinical and radiological changes.

Published
2009
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4. Post-Roe v Wadepsychiatry: legal, clinical, and ethical challenges in psychiatry under abortion bans

Author

Kraguljac, Nina V, Bruns, Debra P, Appelbaum, Paul S, Botello, Erika, King, Victoria L, Remiszewski, Natalie, Widge, Alik S, Alpert, Jonathan E, Carpenter, Linda L, Grzenda, Adrienne, Krystal, John H, McDonald, William M, and Nemeroff, Charles B

Abstract

In recent history, the world has witnessed a trend towards liberalization of abortion laws driven by an increasing understanding of the negative personal and public health consequences of criminalizing abortion. By contrast, several countries have recently implemented restrictive reproductive laws, joining the 112 countries where access to abortion care is banned completely or with narrow exceptions. On June 24, 2022, the US Supreme Court ruling in Dobbs v Jackson Women's Health Organizationoverturned its landmark decisions in Roe v Wadethat established abortion until the point of viability of the fetus as a constitutional right. After Roe v Wadehaving been overturned, it is projected that many women in the USA will be prevented from accessing safe abortion care. Importantly, abortion bans not only impose constraints on patient autonomy, they also restrict physicians' ability to practice evidence-based medicine, which will negatively impact psychiatric care. It is therefore crucial for the practicing psychiatrist to be familiar with this new legal landscape. In this Personal View, we aim to provide a topical overview to help clinicians gain a clear understanding of legal, clinical, and ethical responsibilities, focusing on the USA. We also discuss the reality that psychiatrists might be called upon to determine medical necessity for an abortion on psychiatric grounds, which is new for most US psychiatrists. We predict that psychiatrists will be confronted with very difficult situations in which lawful and ethical conduct might be incongruent, and that abortion bans will result in greater numbers of patients needing psychiatric care from a system that is ill-prepared for additional demands.

Published
2024
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13. Contrasting Case-Control and Normative Reference Approaches to Capture Clinically Relevant Structural Brain Abnormalities in Patients With First-Episode Psychosis Who Are Antipsychotic Naive.

Author

Remiszewski, Natalie, Bryant, James Edward, Rutherford, Saige E., Marquand, Andre F., Nelson, Eric, Askar, Ibrahim, Lahti, Adrienne Carol, and Kraguljac, Nina Vanessa

Subjects
DRUG therapy for psychoses, BRAIN, CLINICAL trials, ANTIPSYCHOTIC agents, MAGNETIC resonance imaging, LONGITUDINAL method, CASE-control method, PSYCHOSES, PHARMACODYNAMICS
Abstract

Importance: To make progress toward precision psychiatry, it is crucial to move beyond case-control studies and instead capture individual variations and interpret them in the context of a normal range of biological systems.Objective: To evaluate whether baseline deviations from a normative reference range in subcortical volumes are better predictors of antipsychotic treatment response than raw volumes in patients with first-episode psychosis (FEP) who were naive to antipsychotic medication.Design, Setting, and Participants: In this prospective longitudinal study, patients with first-episode psychosis who were referred from different clinical settings (emergency department, inpatient units, and outpatient clinics) at the University of Alabama at Birmingham were included. A total of 286 patients were screened, 114 consented, 104 enrolled in the treatment trial, and 85 completed the trial. Patients were observed for 16 weeks. Controls were matched by age and sex. Data were collected between June 2016 and July 2021, and data were analyzed from August 2021 to June 2022.Interventions: Risperidone on a flexible dosing scheme for 16 weeks. There was an option to switch to aripiprazole for excessive adverse effects.Main Outcomes and Measures: The main outcome of this study was to evaluate, in patients with FEP who were naive to antipsychotic medication, the association of baseline raw volumes and volume deviations in subcortical brain regions with response to antipsychotic medication. Raw brain volumes or volume deviation changes after treatment were not examined.Results: Of 190 included participants, 111 (58.4%) were male, and the mean (SD) age was 23.7 (5.5) years. Volumes and deviations were quantified in 98 patients with FEP, and data from 92 controls were used as comparison for case-control contrasts and reference curve calibration. In case-control contrasts, patients with FEP had lower raw thalamus (P = .002; F = 9.63; df = 1), hippocampus (P = .009; F = 17.23; df = 1), amygdala (P = .01; F = 6.55; df = 1), ventral diencephalon (P = .03; F = 4.84; df = 1), and brainstem volumes (P = .004; F = 8.39; df = 1). Of 98 patients, 36 patients with FEP (36%) displayed extreme deviations. Associations with treatment response significantly differed between raw volume and deviation measures in the caudate (z = -2.17; P = .03) and putamen (z = -2.15; P = .03).Conclusions and Relevance: These data suggest that normative modeling allows capture of interindividual heterogeneity of regional brain volumes in patients with FEP and characterize structural pathology in a clinically relevant fashion. This holds promise for progress in precision medicine in psychiatry, where group-level studies have failed to derive reliable maps of structural pathology. [ABSTRACT FROM AUTHOR]

Published
2022
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19. Impact of muscle mass on survival of patients with hepatocellular carcinoma after liver transplantation beyond the Milan criteria

Author

Beumer, Berend R., Vugt, Jeroen L.A., Sapisochin, Gonzalo, Yoon, Peter, Bongini, Marco, Lu, Di, Xu, Xiao, De Simone, Paolo, Pintore, Lorenzo, Golse, Nicolas, Nowosad, Malgorzata, Bennet, William, Tsochatzis, Emmanouil, Koutli, Evangelia, Abbassi, Fariba, Claasen, Marco P.A.W., Merli, Manuela, O'Rourke, Joanne, Gambato, Martina, Benito, Alberto, Majumdar, Avik, Tan, Ek Khoon, Ebadi, Maryam, Montano‐Loza, Aldo J., Berenguer, Marina, Metselaar, Herold J., Polak, Wojciech G., Mazzaferro, Vincenzo, IJzermans, Jan N.M., Haider, Masoom A., Salinas‐Miranda, Emmanuel, Bhoori, Sherrie, Rossi, Piercarlo, Remiszewski, Piotr, Korzeniowski, Krzysztof, Arico, Francesco, Toso, Christian, Ferri, Flaminia, Shah, Tahir, Puchades, Lorena, Herreras, Julia, De Man, Rob A., and Van Klaveren, David

Abstract

Access to the liver transplant waitlist for patients with hepatocellular carcinoma (HCC) depends on tumour presentation, biology, and response to treatments. The Milan Criteria (MC) represent the benchmark for expanded criteria that incorporate additional prognostic factors. The purpose of this study was to determine the added value of skeletal muscle index (SMI) in HCC patients beyond the MC. Patients with HCC that were transplanted beyond the MC were included in this retrospective multicentre study. SMI was quantified using the Computed Tomography (CT) within 3 months prior to transplantation. Cox regression models were used to identify predictors of overall survival (OS). The discriminative performance of SMI extended Metroticket 2.0 and AFP models was also assessed. Out of 889 patients transplanted outside the MC, 528 had a CT scan within 3 months prior to liver transplantation (LT), of whom 176 (33%) were classified as sarcopenic. The median time between assessment of the SMI and LT was 1.8 months (IQR: 0.77–2.67). The median follow‐up period was 5.1 95% CI [4.7–5.5] years, with a total of 177 recorded deaths from any cause. In a linear regression model with SMI as the dependent variable, only male gender (8.55 95% CI [6.51–10.59], P< 0.001) and body mass index (0.74 95% CI [0.59–0.89], P< 0.001) were significant. Univariable survival analysis of patients with sarcopenia versus patients without sarcopenia showed a significant difference in OS (HR 1.44 95% CI [1.07 − 1.94], P= 0.018). Also the SMI was significant (HR 0.98 95% CI [0.96–0.99], P= 0.014). The survival difference between the lowest SMI quartile versus the highest SMI quartile was significant (log‐rank: P= 0.005) with 5 year OS of 57% and 71%, respectively. Data from 423 patients, describing 139 deaths, was used for multivariate analysis. Both sarcopenia (HR 1.45 95% CI [1.02 − 2.05], P= 0.036) and SMI were (HR 0.98 95% CI [0.95–0.99], P= 0.035) significant. On the survival scale this translates to a 5 year OS difference of 11% between sarcopenia and no sarcopenia. Whereas for SMI, this translates to a survival difference of 8% between first and third quartiles for both genders. Overall, we can conclude that higher muscle mass contributes to a better long‐term survival. However, for individual patients, low muscle mass should not be considered an absolute contra‐indication for LT as its discriminatory performance was limited.

Published
2022
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22. The impact of experience of a transplantation center on the outcomes of orthotopic liver transplantation

Author

Krawczyk, M., Grzelak, I., Zieniewicz, K., Nyckowski, P., Pawlak, J., Michalowicz, B., Patkowski, W., Alsharabi, A., Wroblewski, T., Paluszkiewicz, R., Malkowski, P., Hevelke, P., Pszenny, C., Remiszewski, P., Skwarek, A., Smoter, P., Grodzicki, M., Kornasiewicz, O., Korba, M., Kotulski, M., Dudek, K., Fra̦czek, M., Najnigier, B., Alzayany, M., Paczkowska, A., Gelo, R., Andruszkiewicz, P., Sicinski, M., Jurek-Gelo, A., Swierczewski, J., Giercuszkiewicz, D., Brudkowska, A., Andrzejewska, R., Niewinski, G., Nowak, R., Kosinski, C., Korta, T., Oldakowska-Jedynak, U., Sańko-Resmer, J., Pawlowska, M., Foroncewicz, B., Ziolkowski, J., Niewczas, M., Mucha, K., Senatorski, G., Pa̦czek, L., Leowska, E., Pacho, R., Andrzejewska, M., Rowinski, O., Żurakowski, J., Wroblewska, B., and Gornicka, B.

Published
2003
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23. Vascular complications after liver transplantation

Author

Pawlak, J, Grodzicki, M, Leowska, E, Makowski, P, Michałowicz, B, Nyckowski, P, Rowinski, O, Pacho, R, Zieniewicz, K, Andrzejewska, M, Odakowska, U, Grzelak, I, Patkowski, W, Alsharabi, A, Remiszewski, P, Dudek, K, and Krawczyk, M

Published
2003
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26. Liver Transplantation for Hepatic Trauma: A Study From the European Liver Transplant Registry

Author

Krawczyk, M, Grat, M, Adam, R, Polak, W, Klempnauer, J, Pinna, A, Di Benedetto, F, Filipponi, F, Senninger, N, Foss, A, Rufian-Pena, S, Bennet, W, Pratschke, J, Paul, A, Settmacher, U, Rossi, G, Salizzoni, M, Fernandez-Selles, C, de Rituerto, S, Gomez-Bravo, M, Pirenne, J, Detry, O, Majno, P, Nemec, P, Bechstein, W, Bartels, M, Nadalin, S, Pruvot, F, Mirza, D, Lupo, L, Colledan, M, Tisone, G, Ringers, J, Daniel, J, Torra, R, Gonzalez, E, Canizares, R, Martinez, V, Rodriguez, F, Yilmaz, S, Remiszewski, P, Krawczyk M, Grat M, Adam R, Polak WG, Klempnauer J, Pinna A, Di Benedetto F, Filipponi F, Senninger N, Foss A, Rufian-Pena S, Bennet W, Pratschke J, Paul A, Settmacher U, Rossi G, Salizzoni M, Fernandez-Selles C, de Rituerto STM, Gomez-Bravo MA, Pirenne J, Detry O, Majno PE, Nemec P, Bechstein WO, Bartels M, Nadalin S, Pruvot FR, Mirza DF, Lupo L, Colledan M, Tisone G, Ringers J, Daniel J, Torra RC, Gonzalez EM, Canizares RB, Martinez VCM, Rodriguez FSJ, Yilmaz S, Remiszewski P, Krawczyk, M, Grat, M, Adam, R, Polak, W, Klempnauer, J, Pinna, A, Di Benedetto, F, Filipponi, F, Senninger, N, Foss, A, Rufian-Pena, S, Bennet, W, Pratschke, J, Paul, A, Settmacher, U, Rossi, G, Salizzoni, M, Fernandez-Selles, C, de Rituerto, S, Gomez-Bravo, M, Pirenne, J, Detry, O, Majno, P, Nemec, P, Bechstein, W, Bartels, M, Nadalin, S, Pruvot, F, Mirza, D, Lupo, L, Colledan, M, Tisone, G, Ringers, J, Daniel, J, Torra, R, Gonzalez, E, Canizares, R, Martinez, V, Rodriguez, F, Yilmaz, S, Remiszewski, P, Krawczyk M, Grat M, Adam R, Polak WG, Klempnauer J, Pinna A, Di Benedetto F, Filipponi F, Senninger N, Foss A, Rufian-Pena S, Bennet W, Pratschke J, Paul A, Settmacher U, Rossi G, Salizzoni M, Fernandez-Selles C, de Rituerto STM, Gomez-Bravo MA, Pirenne J, Detry O, Majno PE, Nemec P, Bechstein WO, Bartels M, Nadalin S, Pruvot FR, Mirza DF, Lupo L, Colledan M, Tisone G, Ringers J, Daniel J, Torra RC, Gonzalez EM, Canizares RB, Martinez VCM, Rodriguez FSJ, Yilmaz S, and Remiszewski P

Abstract

Background. Liver transplantation is the most extreme form of surgical management of patients with hepatic trauma, with very limited literature data supporting its use. The aim of this study was to assess the results of liver transplantation for hepatic trauma. Methods. This retrospective analysis based on European Liver Transplant Registry comprised data of 73 recipients of liver transplantation for hepatic trauma performed in 37 centers in the period between 1987 and 2013. Mortality and graft loss rates at 90 days were set as primary and secondary outcome measures, respectively. Results. Mortality and graft loss rates at 90 days were 42.5% and 46.6%, respectively. Regarding general variables, cross-clamping without extracorporeal veno-venous bypass was the only independent risk factor for both mortality (P = 0.031) and graft loss (P = 0.034). Regarding more detailed factors, grade of liver trauma exceeding IV increased the risk of mortality (P = 0.005) and graft loss (P = 0.018). Moreover, a tendency above the level of significance was observed for the negative impact of injury severity score (ISS) on mortality (P = 0.071). The optimal cutoff for ISS was 33, with sensitivity of 60.0%, specificity of 80.0%, positive predictive value of 75.0%, and negative predictive value of 66.7%. Conclusions. Liver transplantation seems to be justified in selected patients with otherwise fatal severe liver injuries, particularly in whom cross-clamping without extracorporeal bypass can be omitted. The ISS cutoff less than 33 may be useful in the selection process.

Published
2016

31. Implementation of a surgical safety checklist for dental implant surgeries in a prosthodontics residency program.

Author

Remiszewski, David P. and Bidra, Avinash S.

Abstract

Surgical safety checklists are commonly used in medical surgery to reduce errors, yet they are rarely used in the dental office. Presently, research on the implementation of surgical safety checklists in implant dentistry and user adherence is lacking. The primary purpose of this quality assessment study was to evaluate user compliance by using a surgical safety checklist for dental implant surgeries in a postgraduate prosthodontics program at the University of Connecticut School of Dental Medicine. The secondary purpose was to identify and analyze the nature, number, and frequency of omitted items on the surgical safety checklist. All surgical safety checklists completed by 8 prosthodontic residents from 120 dental implant surgeries over the course of 1 academic year were collected as part of the program's quality assessment. Each surgical safety checklist contained 12 preoperative items and 14 postoperative items, giving a total of 26 items to be analyzed for each dental implant surgery. The collected data were then analyzed for user compliance, as well as the nature, number, and frequency of omitted items. Surgical safety checklists from 120 dental implant surgeries encompassing 262 implants were accessed for the academic year cycle from July 2017 to June 2018. There were 6 additional dental implant surgeries whose checklists were inaccessible. There was a 100% compliance rate for surgical safety checklist completion by all 8 prosthodontic residents across 120 dental implant surgeries. Within the checklists, the rate of incomplete responses or omissions was 2.4% (n=77). The 5 most commonly omitted items on the checklist by residents were preoperative photographs (0.29%), postoperative analgesics or steroids (0.26%), preoperative oral antiseptic rinse (0.22%), postoperative prescriptions (0.19%), and signed prosthodontic treatment plan forms (0.16%). There was excellent compliance with the implemented dental implant surgical safety checklist across 8 prosthodontic residents, and the number of omitted items was small. Surgical safety checklists appear to be a straightforward method of helping prosthodontic residents in their dental implant surgical training to provide consistent and high-quality safe treatment for patients. [ABSTRACT FROM AUTHOR]

Published
2019
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34. Liver Function in Patients With Nonalcoholic Fatty Liver Disease Randomized to Roux-en-Y Gastric Bypass Versus Sleeve Gastrectomy: A Secondary Analysis of a Randomized Clinical Trial.

Author

Kalinowski, Piotr, Paluszkiewicz, Rafał, Ziarkiewicz-Wróblewska, Bogna, Wróblewski, Tadeusz, Remiszewski, Piotr, Grodzicki, Mariusz, and Krawczyk, Marek

Abstract

Objectives: The aim of the study was to compare the influence of sleeve gastrectomy (SG) versus Roux-en-Y gastric bypass (RYGB) on liver function in bariatric patients with non-alcoholic fatty liver disease (NAFLD) in a randomized clinical trial (NCT01806506). Background: Rapid weight loss and malabsorption after bariatric surgery in patients with NAFLD or steatohepatitis (NASH) may impair liver function. Methods: Sixty-six morbidly obese patients randomized to SG or RYGB were included in a secondary outcome analysis. Intraoperative liver biopsies were categorized with NAFLD Activity Score (NAS) and liver function tests were done before surgery and after 1, 6 and 12 months. Results: NASH was present in 54.5% RYGB and 51.5% SG patients (P > 0.05). At 12 months excess weight loss was 68.7±19.7% after SG and 62.8±18.5% after RYGB (P > 0.05). At 1 month international normalized ratio (INR) increased after RYGB (0.98±0.05 vs 1.14±0.11; P < 0.05) and SG (0.99±0.06 vs 1.04±0.06; P < 0.05), RYGB induced significantly greater increase in INR in the whole group and NASH patients than SG. After RYGB albumin decreased at 1 month (41.2±2.7 vs 39.0±3.2 g/L; P <0.05). At 12 months, INR and albumin returned to baseline. At 12 months in NASH group, SG induced significant improvement in aspartate aminotransferase (32.4±17.4 vs 21.5±6.9U/L), alanine aminotransferase (39.9±28.6U/L vs 23.8±14.1U/L), gamma-glutamyl transpeptidase (34.3±16.6 vs 24.5±16.8U/L), and lactate dehydrogenase (510.8±33 vs 292.4±29). Variables predictive of INR change after 1 month included operation type, NAS ≥ 5, bilirubin, body mass index, hemoglobin A1C, and dyslipidemia. Conclusions: Patients with NASH undergoing RYGB are more susceptible to early transient deterioration of liver function than after SG. [ABSTRACT FROM AUTHOR]

Published
2017
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35. Ghrelin, leptin, and glycemic control after sleeve gastrectomy versus Roux-en-Y gastric bypass—results of a randomized clinical trial.

Author

Kalinowski, Piotr, Paluszkiewicz, Rafał, Wróblewski, Tadeusz, Remiszewski, Piotr, Grodzicki, Mariusz, Bartoszewicz, Zbigniew, and Krawczyk, Marek

Abstract

Background Sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) cause weight loss and metabolic improvement, but results of published studies are contradictory. Objectives The aim of this study was to compare the effects of SG and RYGB on ghrelin, leptin, and glucose homeostasis in a randomized controlled trial. Setting University hospital, Poland. Methods Seventy-two morbidly obese patients were randomly selected to undergo either SG (n = 36) or RYGB (n = 36). Fasting ghrelin, leptin, glucose, insulin, C-peptide, glucagon, glycated hemoglobin, and homeostasis model assessment of insulin resistance were assessed preoperatively and at 1, 6, and 12 months postoperatively. No differences were found in anthropometric and biochemical parameters between the study groups at baseline. Results Sixty-nine (95.8%) patients completed the study. Percentage of excess weight loss at 12 months was 67.6±19.3% after SG and 64.2±18.5% after RYGB ( P >.05). Fasting ghrelin levels decreased 1 month after SG (from 76.8 pmol/L to 35.3 pmol/L; P <.05) and remained reduced until 12 months (41.6 pmol/L; P <.05) but increased 12 months after RYGB from 74.6 pmol/L to 130.2 pmol/L ( P <.05). Leptin, glucose, insulin, and C-peptide concentrations and glycated hemoglobin and homeostasis model assessment of insulin resistance values decreased significantly in both groups during 12 months. Conclusions RYGB and SG induce comparable weight loss and improvement in metabolism of glucose. Ghrelin levels decrease after SG and increase after RYGB, but this difference does not affect similar outcomes of these procedures during 1-year follow-up. The contribution of ghrelin to weight loss or metabolic benefits after bariatric surgery is not straightforward, but rather influenced by multiple factors. [ABSTRACT FROM AUTHOR]

Published
2017
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36. Intraoperative Single-Pass Batch Sustained Low Efficiency Dialysis (SLED) in Orthotopic Liver Transplantation (OLT).

Author

Matuszkiewicz-Rowinska, J., primary, Zebrowski, P., additional, Niewinski, G., additional, Patkowski, W., additional, Mieczkowski, M., additional, Kulicki, P., additional, Giercuszkiewicz, D., additional, Nyckowski, P., additional, Dudek, K., additional, Remiszewski, P., additional, Figiel, W., additional, Pyrza, M., additional, Zieniewicz, K., additional, Wroblewski, T., additional, Kanski, A., additional, and Krawczyk, M., additional

Published
2014
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37. [Sarcoid reaction in patients with lung neoplasm--personal experiments]

Author

Remiszewski P, Mariusz Chabowski, Tm, Orłowski, Langfort R, Bestry I, Marzinek M, and Rowińska-Zakrzewska E

Subjects
Male, Granuloma, Lung Neoplasms, Sarcoidosis, Adenocarcinoma, Middle Aged, Diagnosis, Differential, Radiography, Carcinoma, Non-Small-Cell Lung, Lymphatic Metastasis, Disease Progression, Humans, Lymph Node Excision, Female, Lymph Nodes, Lung, Precancerous Conditions, Aged
Abstract

In two cases histological examination of the lymph nodes excised during mediastinoscopy showed non-caseous epithelioid granulomas. In one patient with hilar lymphadenopathy sarcoidosis was misdiagnosed. One-year later progression of lesions in lungs was found and adenocarcinoma was diagnosed. In second patient with tumour in chest x-ray examination after misdiagnosed sarcoidosis thoracotomy was done and histological examination of samples from tumour showed nonsmall cell lung cancer. In both carcinomatous cases sarcoid reaction was recognised.

Published
2001

39. Hepatic Epithelioid Hemangioendothelioma and Adult Liver Transplantation: Proposal for a Prognostic Score Based on the Analysis of the ELTR-ELITA Registry

Author

Lai, Quirino, Feys, Estelle, Karam, Vincent, Adam, Rene, Klempnauer, Jurgen, Oliverius, Martin, Mazzaferro, Vincenzo, Pascher, Andreas, Remiszewski, Piotr, Isoniemi, Helena, Pirenne, Jacques, Foss, Aksel, Ericzon, Bo G., Markovic, Sasa, and Lerut, Jan P.

Abstract

This study updates the ELTR experience with HEHE. The findings from this larger cohort substantiate the role of OLT in HEHE and identify rapid transplantation and microvascular invasion as predictors of poor outcomes while extrahepatic disease is not. The authors also affirm the overall improvement in outcomes that seem primarily reflective of improved patient selection.

Published
2017
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40. Liver Transplantation for Hepatic Trauma: A Study From the European Liver Transplant Registry

Author

Krawczyk, Marek, Grąt, Michał, Adam, Rene, Polak, Wojciech G., Klempnauer, Jurgen, Pinna, Antonio, Di Benedetto, Fabrizio, Filipponi, Franco, Senninger, Norbert, Foss, Aksel, Rufián-Peña, Sebastian, Bennet, William, Pratschke, Johann, Paul, Andreas, Settmacher, Utz, Rossi, Giorgio, Salizzoni, Mauro, Fernandez-Selles, Carlos, Martínez de Rituerto, Santiago T., Gómez-Bravo, Miguel A., Pirenne, Jacques, Detry, Olivier, Majno, Pietro E., Nemec, Petr, Bechstein, Wolf O., Bartels, Michael, Nadalin, Silvio, Pruvot, Francois R., Mirza, Darius F., Lupo, Luigi, Colledan, Michele, Tisone, Giuseppe, Ringers, Jan, Daniel, Jorge, Charco Torra, Ramón, Moreno González, Enrique, Bañares Cañizares, Rafael, Cuervas-Mons Martinez, Valentin, San Juan Rodríguez, Fernando, Yilmaz, Sezai, and Remiszewski, Piotr

Abstract

Hepatic trauma is a rare indication for liver transplantation. This collection of cases from the European Liver Transplant Registry provides guidance for indications and results demonstrating improved outcomes over time. Supplemental digital content is available in the text.

Published
2016
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44. Optimization of Benzodiazepinonesas Selective Inhibitorsof the X-Linked Inhibitor of Apoptosis Protein (XIAP) SecondBaculovirus IAP Repeat (BIR2) Domain.

Author

Kester, Robert F., Donnell, Andrew F., Lou, Yan, Remiszewski, Stacy W., Lombardo, Louis J., Chen, Shaoqing, Le, Nam T., Lo, Jennifer, Moliterni, John A., Han, Xiaochun, Hogg, J. Heather, Liang, Weiling, Michoud, Christophe, Rupert, Kenneth C., Mischke, Steven, Le, Kang, Weisel, Martin, Janson, Cheryl A., Lukacs, Christine M., and Fretland, Adrian J.

Published
2013
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45. Combined Heart-Liver Transplantation – First Series In Poland.

Author

Zieniewicz, Krzysztof, Kusmierczyk, Mariusz, Dudek, Krzysztof, Kotulski, Marcin, Remiszewski, Piotr, Wroblewski, Tadeusz, Krasnodebski, Maciej, Niewinski, Grzegorz, Sitkowska-Rysiak, Ewa, Raszeja-Wyszomirska, Joanna, Sobieszczanska-Malek, Malgorzata, Zielinski, Tomasz, and Zajac, Krzysztof

Published
2020
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47. The Discovery of NVP-LAQ824: From Concept to Clinic

Author

Remiszewski, Stacy

Abstract

The natural products trapoxin B and trichostatin A, as well as the novel marine natural product psammaplin A (PSMA) were found in a cell-based screen for compounds that induced the expression of the cyclin dependent kinase inhibitor p21waf1. The mechanism of p21waf1 induction for these compounds was via histone deacetylase (HDAC) inhibition. Of these compounds, PSMA was of interest because of its novel structure, but the physiological stability of it, and its analogs was poor. Thus, a directed medicinal chemistry effort was undertaken to prepare analogs of the simple HDAC inhibitor dimethylaminobenzamidylcaprylic hydroxamate (DBCH), which led to chromenone amide 9. This compound was efficacious in the HCT116 colon xenograft assay, but was difficult to formulate in pharmaceutically acceptable vehicles. In parallel with these efforts, a screen of the Novartis compound archive for novel HDAC inhibitors uncovered the cinnamyl hydroxamic acid NVP-LAK974. This compound had good enzyme and cellular potency, but poor efficacy in vivo. A systematic structural exploration of cinnamyl hydroxamates based on NVP-LAK974 was undertaken with the goal of finding a novel, well-tolerated and efficacious HDAC inhibitor. Several derivatives were found to be efficacious in the xenograft assay. Of those compounds, NVP-LAQ824 distinguished itself due to its tolerability, efficacy and potency. Based, in part, on these properties, NVP-LAQ824 is currently undergoing human clinical trials as a novel anti-cancer agent.

Published
2003

48. N-Hydroxy-3-phenyl-2-propenamides as Novel Inhibitors of Human Histone Deacetylase with in Vivo Antitumor Activity:  Discovery of (2E)-N-Hydroxy-3-[4-[[(2-hydroxyethyl)[2-(1H-indol-3-yl)ethyl]amino]methyl]phenyl]-2-propenamide (NVP-LAQ824)

Author

Remiszewski, S. W., Sambucetti, L. C., Bair, K. W., Bontempo, J., Cesarz, D., Chandramouli, N., Chen, R., Cheung, M., Cornell-Kennon, S., Dean, K., Diamantidis, G., France, D., Green, M. A., Howell, K. L., Kashi, R., Kwon, P., Lassota, P., Martin, M. S., Mou, Y., Perez, L. B., Sharma, S., Smith, T., Sorensen, E., Taplin, F., Trogani, N., Versace, R., Walker, H., Weltchek-Engler, S., Wood, A., Wu, A., and Atadja, P.

Abstract

A series of N-hydroxy-3-phenyl-2-propenamides were prepared as novel inhibitors of human histone deacetylase (HDAC). These compounds were potent enzyme inhibitors, having IC50s &lt; 400 nM in a partially purified enzyme assay. However, potency in cell growth inhibition assays ranged over 2 orders of magnitude in two human carcinoma cell lines. Selected compounds having cellular IC50 &lt; 750 nM were tested for maximum tolerated dose (MTD) and for efficacy in the HCT116 human colon tumor xenograft assay. Four compounds having an MTD ≥ 100 mg/kg were selected for dose−response studies in the HCT116 xenograft model. One compound, 9 (NVP-LAQ824), had significant dose-related activity in the HCT116 colon and A549 lung tumor models, high MTD, and low gross toxicity. On the basis, in part, of these properties, 9 has entered human clinical trials in 2002.

Published
2003

49. NVP-LAQ824 is a potent novel histone deacetylase inhibitor with significant activity against multiple myeloma

Author

Catley, Laurence, Weisberg, Ellen, Tai, Yu-Tzu, Atadja, Peter, Remiszewski, Stacy, Hideshima, Teru, Mitsiades, Nicholas, Shringarpure, Reshma, LeBlanc, Richard, Chauhan, Dharminder, Munshi, Nikhil C., Schlossman, Robert, Richardson, Paul, Griffin, James, and Anderson, Kenneth C.

Abstract

Histone deacetylase (HDAC) inhibitors are emerging as a promising new treatment strategy in hematologic malignancies. Here we show that NVP-LAQ824, a novel hydroxamic acid derivative, induces apoptosis at physiologically achievable concentrations (median inhibitory concentration [IC50] of 100 nM at 24 hours) in multiple myeloma (MM) cell lines resistant to conventional therapies. MM.1S myeloma cell proliferation was also inhibited when cocultured with bone marrow stromal cells, demonstrating ability to overcome the stimulatory effects of the bone marrow microenvironment. Importantly, NVP-LAQ824 also inhibited patient MM cell growth in a dose- and time-dependent manner. NVP-LAQ824-induced apoptotic signaling includes up-regulation of p21, caspase cascade activation, and poly (adenosine diphosphate [ADP]) ribose (PARP) cleavage. Apoptosis was confirmed with cell cycle analysis and annexin-propidium iodide staining. Interestingly, treatment of MM cells with NVPLAQ824 also led to proteasome inhibition, as determined by reduced proteasome chymotrypsin-like activity and increased levels of cellular polyubiquitin conjugates. Finally, a study using NVP-LAQ824 in a preclinical murine myeloma model provides in vivo relevance to our in vitro studies. Taken together, these findings provide the framework for NVP-LAQ824 as a novel therapeutic in MM. (Blood. 2003;102:2615-2622)

Published
2003
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50. Inhibitors of Human Histone Deacetylase:  Synthesis and Enzyme and Cellular Activity of Straight Chain Hydroxamates

Author

Remiszewski, S. W., Sambucetti, L. C., Atadja, P., Bair, K. W., Cornell, W. D., Green, M. A., Howell, K. L., Jung, M., Kwon, P., Trogani, N., and Walker, H.

Abstract

Inhibitors of histone deacetylase (HDAC) have been shown to induce terminal differentiation of human tumor cell lines and to have antitumor effects in vivo. We have prepared analogues of suberoylanilide hydroxamic acid (SAHA) and trichostatin A and have evaluated them in a human HDAC enzyme inhibition assay, a p21waf1 (p21) promoter assay, and in monolayer growth inhibition assays. One compound, 4-(dimethylamino)-N-[7-(hydroxyamino)-7-oxoheptyl]-benzamide, was found to affect the growth of a panel of eight human tumor cell lines differentially.

Published
2002
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