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Article ; Online: How Does a Patient's Primary Renal Disease Impact Chronic Dialysis Management?: Patients with Autosomal Dominant Polycystic Kidney Disease.

Amro, Osama W / Perrone, Ronald D

2015 Volume 28, Issue 5, Page(s) 470–473

MeSH term(s)	Disease Management ; Humans ; Kidney Failure, Chronic/etiology ; Kidney Failure, Chronic/therapy ; Polycystic Kidney, Autosomal Dominant/complications ; Renal Dialysis
Language	English
Publishing date	2015-09
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1028193-9
ISSN	1525-139X ; 0894-0959
ISSN (online)	1525-139X
ISSN	0894-0959
DOI	10.1111/sdi.12397
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Article ; Online: Low-Osmolar Diet and Adjusted Water Intake for Vasopressin Reduction in Autosomal Dominant Polycystic Kidney Disease: A Pilot Randomized Controlled Trial.

Amro, Osama W / Paulus, Jessica K / Noubary, Farzad / Perrone, Ronald D

American journal of kidney diseases : the official journal of the National Kidney Foundation

2016 Volume 68, Issue 6, Page(s) 882–891

Abstract: Background: Autosomal dominant polycystic kidney disease (ADPKD) affects millions of people worldwide. Vasopressin promotes disease progression.: Study design: A randomized controlled trial with equal (1:1) allocation.: Setting & participants: ... ...

Abstract	Background: Autosomal dominant polycystic kidney disease (ADPKD) affects millions of people worldwide. Vasopressin promotes disease progression. Study design: A randomized controlled trial with equal (1:1) allocation. Setting & participants: This trial examined the effect of combining a low-osmolar (low-sodium [1,500mg/d], low-protein [0.8g per kilogram of body weight]) diet and adjusted water intake on vasopressin secretion in 34 patients with ADPKD. Intervention: Participants were randomly assigned to receive a low-osmolar diet followed by adjusted water intake to achieve urine osmolality ≤ 280mOsm/kg water versus no intervention for 2 weeks. Outcome: The primary outcome of the study was change (delta) in copeptin levels and urine osmolality between the intervention and control groups from baseline to 2 weeks. Measurements: Fasting plasma copeptin level, 24-hour urine osmolality, and total solute intake. Results: Baseline characteristics of the 2 groups were similar. Mean plasma copeptin levels and urine osmolality declined from 6.2±3.05 (SD) to 5.3±2.5pmol/L (P=0.02) and from 426±193 to 258±117mOsm/kg water (P=0.01), respectively, in the intervention group compared to a nonsignificant change in the control group (from 4.7±3.6 to 5.07±4pmol/L [P=0.2] and 329±159 to 349±139mOsm/kg water [P=0.3], respectively). The change in copeptin levels (primary outcome) and urine osmolality was statistically significant between the intervention and control groups (delta copeptin, -0.86±1.3 vs +0.39±1.2pmol/L [P=0.009]; delta urine osmolality, -167±264 vs +20±80mOsm/kg water [P=0.007], respectively). Total urinary solute decreased in only the intervention group and significantly differed between groups at week 1 (P=0.03), reducing mean water prescription from 3.2 to 2.6L/d. Limitations: Small sample size and short follow-up. Conclusions: We developed a stepwise dietary intervention that led to a significant reduction in vasopressin secretion in patients with ADPKD. Furthermore, this intervention led to a reduction in water required for vasopressin reduction.
MeSH term(s)	Adolescent ; Adult ; Arginine Vasopressin/metabolism ; Arginine Vasopressin/urine ; Drinking ; Female ; Humans ; Male ; Middle Aged ; Osmolar Concentration ; Pilot Projects ; Polycystic Kidney, Autosomal Dominant/diet therapy ; Polycystic Kidney, Autosomal Dominant/urine ; Young Adult
Chemical Substances	Arginine Vasopressin (113-79-1)
Language	English
Publishing date	2016-09-20
Publishing country	United States
Document type	Journal Article ; Randomized Controlled Trial
ZDB-ID	604539-x
ISSN	1523-6838 ; 0272-6386
ISSN (online)	1523-6838
ISSN	0272-6386
DOI	10.1053/j.ajkd.2016.07.023
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Zs.A 1669: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Nosocomial Infections among Patients with Intracranial Hemorrhage: A Retrospective Data Analysis of Predictors and Outcomes.

Jaradat, Roa'a W / Lahlouh, Amro B / Alshogran, Osama Y / Aldabbour, Belal A / Balusha, Abedallah Ak

Clinical neurology and neurosurgery

2019 Volume 182, Page(s) 158–166

Abstract: Objective: Intracranial hemorrhage is a critical medical emergency. Nosocomial infections may promote worse outcomes in these vulnerable patients. This study investigated microbial features, predictors, and clinical outcomes of nosocomial infections ... ...

Abstract	Objective: Intracranial hemorrhage is a critical medical emergency. Nosocomial infections may promote worse outcomes in these vulnerable patients. This study investigated microbial features, predictors, and clinical outcomes of nosocomial infections among patients with multiple subtypes of intracranial hemorrhage. Patients and methods: We conducted a retrospective cohort study of patients that were hospitalized with intracranial hemorrhage between January 2015 and October 2018, and divided them into two groups based on the development of nosocomial infection. Within the cohort of patients with nosocomial infections, microbiology and resistance patterns were established across multiple sites of infection. Moreover, consequences of nosocomial infection such as mortality and length of hospital stay were determined. Results: A total of 233 cases were identified that met our inclusion and exclusion criteria out of which were 94 cases of nosocomial infection (40.3%) versus 139 cases with no nosocomial infection (59.7%). The most common infections were pneumonia, urinary tract infections, and bacteremia. Resistance accounted for 70.2% of cultures. Multivariable analysis revealed significant association of nosocomial infections with hypertension (OR: 2.62, 95% CI: 1.11-6.16, p = 0.027), hospital LOS (OR: 1.08, 95% CI: 1.05-1.12, p < 0.001), levetiracetam (OR: 3.6, 95% CI: 1.41-0.922, p = 0.007), and GCS category (OR: 5.42, 95% CI: 1.67-17.55, p = 0.005 and OR: 7.63, 95% CI: 2.44-23.87, p < 0.001 for moderate and severe, respectively). Patients with nosocomial infections witnessed a significant increase in the length of hospital stay (23 versus 8 hospital days, p < 0.001). This finding was significant across most types of brain hemorrhage. Mortality was significantly associated with GCS category (OR: 10.1, 95% CI: 4-25.7, p < 0.001) and percutaneous endoscopic gastrostomy tube insertion (OR: 19.6, 95% CI: 4.1-91, p < 0.001). Conclusions: Collectively, these findings suggest that nosocomial infections are common among patients with intracranial hemorrhage and can be predictable by considering certain risk factors. Future studies are warranted to evaluate the efficacy of implementing infection control strategies or protocols on these patients to achieve better therapeutic outcomes.
MeSH term(s)	Cross Infection/complications ; Cross Infection/diagnosis ; Cross Infection/surgery ; Data Analysis ; Female ; Humans ; Intensive Care Units/statistics & numerical data ; Intracranial Hemorrhages/complications ; Intracranial Hemorrhages/surgery ; Length of Stay/statistics & numerical data ; Male ; Middle Aged ; Pneumonia/diagnosis ; Pneumonia/surgery ; Retrospective Studies ; Risk Factors
Language	English
Publishing date	2019-05-20
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	193107-6
ISSN	1872-6968 ; 0303-8467
ISSN (online)	1872-6968
ISSN	0303-8467
DOI	10.1016/j.clineuro.2019.05.016
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Article ; Online: Anticancer Efficacy of KRASG12C Inhibitors Is Potentiated by PAK4 Inhibitor KPT9274 in Preclinical Models of KRASG12C-Mutant Pancreatic and Lung Cancers.

Molecular cancer therapeutics

2023 Volume 22, Issue 12, Page(s) 1422–1433

Abstract: KRASG12C inhibitors, such as sotorasib and adagrasib, have revolutionized cancer treatment for patients with KRASG12C-mutant tumors. However, patients receiving these agents as monotherapy often develop drug resistance. To address this issue, we ... ...

Abstract	KRASG12C inhibitors, such as sotorasib and adagrasib, have revolutionized cancer treatment for patients with KRASG12C-mutant tumors. However, patients receiving these agents as monotherapy often develop drug resistance. To address this issue, we evaluated the combination of the PAK4 inhibitor KPT9274 and KRASG12C inhibitors in preclinical models of pancreatic ductal adenocarcinoma (PDAC) and non-small cell lung cancer (NSCLC). PAK4 is a hub molecule that links several major signaling pathways and is known for its tumorigenic role in mutant Ras-driven cancers. We found that cancer cells resistant to KRASG12C inhibitor were sensitive to KPT9274-induced growth inhibition. Furthermore, KPT9274 synergized with sotorasib and adagrasib to inhibit the growth of KRASG12C-mutant cancer cells and reduce their clonogenic potential. Mechanistically, this combination suppressed cell growth signaling and downregulated cell-cycle markers. In a PDAC cell line-derived xenograft (CDX) model, the combination of a suboptimal dose of KPT9274 with sotorasib significantly reduced the tumor burden (P= 0.002). Similarly, potent antitumor efficacy was observed in an NSCLC CDX model, in which KPT9274, given as maintenance therapy, prevented tumor relapse following the discontinuation of sotorasib treatment (P= 0.0001). Moreover, the combination of KPT9274 and sotorasib enhances survival. In conclusion, this is the first study to demonstrate that KRASG12C inhibitors can synergize with the PAK4 inhibitor KPT9274 and combining KRASG12C inhibitors with KPT9274 can lead to remarkably enhanced antitumor activity and survival benefits, providing a novel combination therapy for patients with cancer who do not respond or develop resistance to KRASG12C inhibitor treatment.
MeSH term(s)	Humans ; Lung Neoplasms/drug therapy ; Lung Neoplasms/genetics ; Lung Neoplasms/pathology ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Carcinoma, Non-Small-Cell Lung/genetics ; Carcinoma, Non-Small-Cell Lung/pathology ; Protein Kinase Inhibitors/pharmacology ; Protein Kinase Inhibitors/therapeutic use ; Pancreatic Neoplasms/drug therapy ; Pancreatic Neoplasms/genetics ; Pancreatic Neoplasms/metabolism ; Carcinoma, Pancreatic Ductal/drug therapy ; Proto-Oncogene Proteins p21(ras)/genetics ; Proto-Oncogene Proteins p21(ras)/metabolism ; p21-Activated Kinases/genetics ; Pancreatic Neoplasms
Chemical Substances	adagrasib (8EOO6HQF8Y) ; Protein Kinase Inhibitors ; Proto-Oncogene Proteins p21(ras) (EC 3.6.5.2) ; PAK4 protein, human (EC 2.7.1.11) ; p21-Activated Kinases (EC 2.7.11.1)
Language	English
Publishing date	2023-09-13
Publishing country	United States
Document type	Journal Article
ZDB-ID	2063563-1
ISSN	1538-8514 ; 1535-7163
ISSN (online)	1538-8514
ISSN	1535-7163
DOI	10.1158/1535-7163.MCT-23-0251
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Zs.A 5750: Show issues

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Article ; Online: Nephrologist-Facilitated Advance Care Planning for Hemodialysis Patients: A Quality Improvement Project.

Amro, Osama W / Ramasamy, Malar / Strom, James A / Weiner, Daniel E / Jaber, Bertrand L

American journal of kidney diseases : the official journal of the National Kidney Foundation

2016 Volume 68, Issue 1, Page(s) 103–109

Abstract: Background: The Renal Physicians Association's clinical practice guideline recommends that physicians address advance care planning with dialysis patients. However, data are lacking about how best to implement this recommendation.: Study design: ... ...

Abstract	Background: The Renal Physicians Association's clinical practice guideline recommends that physicians address advance care planning with dialysis patients. However, data are lacking about how best to implement this recommendation. Study design: Quality improvement project. Settings & participants: Nephrologists caring for patients treated with maintenance hemodialysis at 2 dialysis facilities identified patients who might benefit most from advance care planning using the "surprise" question ("Would I be surprised if this patient died in the next year?"). Quality improvement plan: Patients identified with a "no" response to the surprise question were invited to participate in nephrologist-facilitated advance care planning, including completion of a Medical Orders for Life-Sustaining Treatment (MOLST) form. Outcomes: Change in MOLST completion rate and identification of preferences for limits on life-sustaining treatment. Measurements: Pre- and postintervention code status, MOLST completion rate, and vital status at 1 year. Results: Nephrologists answered "no" to the surprise question for 50 of 201 (25%) hemodialysis patients. Of these, 41 (82%) patients had a full-code status and 9 (18%) had a do-not-resuscitate (DNR) status. Encounters lasted 15 to 60 minutes. Following the encounter, 21 (42%) patients expressed preference for a DNR status and 29 (58%) maintained full-code status (P=0.001). The MOLST completion rate increased from 10% to 90%. One-year survival for patients whose nephrologists answered "no" to the surprise question was 58% compared to 92% for those with a "yes" answer (P<0.001). Limitations: Sample size and possible nonrepresentative dialysis population. Conclusions: Nephrologist-facilitated advance care planning targeting hemodialysis patients with limited life expectancy led to significant changes in documented patient preferences for cardiopulmonary resuscitation and limits on life-sustaining treatment. These changes demonstrate the benefit of advance care planning with dialysis patients and likely reflect better understanding of end-of-life treatment options.
MeSH term(s)	Advance Care Planning ; Aged ; Female ; Humans ; Male ; Middle Aged ; Nephrologists ; Quality Improvement ; Renal Dialysis
Language	English
Publishing date	2016-07
Publishing country	United States
Document type	Journal Article ; Multicenter Study
ZDB-ID	604539-x
ISSN	1523-6838 ; 0272-6386
ISSN (online)	1523-6838
ISSN	0272-6386
DOI	10.1053/j.ajkd.2015.11.024
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Zs.A 1669: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article: Acute kidney injury in allopurinol-induced DRESS syndrome: a case report of concurrent tubulointerstitial nephritis and kidney-limited necrotizing vasculitis .

Esposito, Anthony J / Murphy, Ryan C / Toukatly, Mirna N / Amro, Osama W / Kestenbaum, Bryan R / Najafian, Behzad

Clinical nephrology

2017 Volume 87, Issue 6, Page(s) 316–319

Abstract: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare but potentially fatal adverse drug reaction with variable renal involvement. We report the case of a man who presented with allopurinol-induced DRESS and acute kidney injury (AKI) ... ...

Abstract	Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare but potentially fatal adverse drug reaction with variable renal involvement. We report the case of a man who presented with allopurinol-induced DRESS and acute kidney injury (AKI) requiring hemodialysis. Kidney biopsy revealed eosinophilic tubulointerstitial nephritis and necrotizing vasculitis of the intralobular arteries without systemic markers of vasculitis. After cyclophosphamide and glucocorticoids, his symptoms and AKI resolved. To our knowledge, this is the first case of kidney-limited necrotizing vasculitis, questioning whether a biopsy should be routinely performed in patients with DRESS accompanied by severe AKI. It is possible that kidney-limited necrotizing vasculitis is an under-diagnosed manifestation of DRESS syndrome, and in such a setting, early recognition, stopping the offending agent, and use of aggressive immunosuppressive therapy, including cyclophosphamide, may lead to a favorable outcome. .
MeSH term(s)	Acute Kidney Injury ; Allopurinol/adverse effects ; Drug Hypersensitivity Syndrome ; Humans ; Male ; Middle Aged ; Necrosis/complications ; Nephritis, Interstitial/complications ; Vasculitis/complications
Chemical Substances	Allopurinol (63CZ7GJN5I)
Language	English
Publishing date	2017-06
Publishing country	Germany
Document type	Case Reports ; Journal Article
ZDB-ID	185101-9
ISSN	0301-0430
ISSN	0301-0430
DOI	10.5414/CN108966
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Article: Anticancer efficacy of KRASG12C inhibitors is potentiated by PAK4 inhibitor KPT9274 in preclinical models of KRASG12C mutant pancreatic and lung cancers.

bioRxiv : the preprint server for biology

2023

Abstract: KRASG12C inhibitors have revolutionized the treatment landscape for cancer patients harboring the G12C mutant isoform of KRAS. With the recent FDA approval of sotorasib and adagrasib, patients now have access to more promising treatment options. However, ...

Abstract	KRASG12C inhibitors have revolutionized the treatment landscape for cancer patients harboring the G12C mutant isoform of KRAS. With the recent FDA approval of sotorasib and adagrasib, patients now have access to more promising treatment options. However, patients who receive these agents as a monotherapy usually develop drug resistance. Thus, there is a need to develop logical combination strategies that can delay or prevent the onset of resistance and simultaneously enhance the antitumor effectiveness of the treatment regimen. In this study, we aimed at pharmacologically targeting PAK4 by KPT9274 in combination with KRASG12C inhibitors in KRASG12C mutant pancreatic ductal adenocarcinoma (PDAC) and nonâ€"small cell lung cancer (NSCLC) preclinical models. PAK4 is a hub molecule that links several major signaling pathways and is known for its tumorigenic role in mutant Ras-driven cancers. We assessed the cytotoxicity of PAK4 and KRASG12C inhibitors combination in KRASG12C mutant 2D and 3D cellular models. KPT9274 synergized with both sotorasib and adagrasib in inhibiting the growth of KRASG12C mutant cancer cells. The combination was able to reduce the clonogenic potential of KRASG12C mutant PDAC cells. We also evaluated the antitumor activity of the combination in a KRASG12C mutant PDAC cell line-derived xenograft (CDX) model. Oral administration of a sub-optimal dose of KPT9274 in combination with sotorasib (at one-fourth of MTD) demonstrated significant inhibition of the tumor burden ( Significance: KRASG12C inhibitors demonstrate limited durable response in patients with KRASG12C mutations. In this study, combining PAK4 inhibitor KPT9274 with KRASG12C inhibitors has resulted in potent antitumor effects in preclinical cancer models of PDAC and NSCLC. Our results bring forward a novel combination therapy for cancer patients that do not respond or develop resistance to KRASG12C inhibitor treatment.
Language	English
Publishing date	2023-03-27
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.03.27.534309
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Article ; Online: How Does a Patient's Primary Renal Disease Impact Chronic Dialysis Management?: Patients with Autosomal Dominant Polycystic Kidney Disease.

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Article ; Online: Low-Osmolar Diet and Adjusted Water Intake for Vasopressin Reduction in Autosomal Dominant Polycystic Kidney Disease: A Pilot Randomized Controlled Trial.

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Article ; Online: Nosocomial Infections among Patients with Intracranial Hemorrhage: A Retrospective Data Analysis of Predictors and Outcomes.

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Article ; Online: Anticancer Efficacy of KRASG12C Inhibitors Is Potentiated by PAK4 Inhibitor KPT9274 in Preclinical Models of KRASG12C-Mutant Pancreatic and Lung Cancers.

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Article ; Online: Nephrologist-Facilitated Advance Care Planning for Hemodialysis Patients: A Quality Improvement Project.

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Article: Acute kidney injury in allopurinol-induced DRESS syndrome: a case report of concurrent tubulointerstitial nephritis and kidney-limited necrotizing vasculitis .

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Article: Anticancer efficacy of KRASG12C inhibitors is potentiated by PAK4 inhibitor KPT9274 in preclinical models of KRASG12C mutant pancreatic and lung cancers.

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