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Article: Gastrointestinal Stromal Tumor of the Appendix.

Elnassasra, Ahmad / Hershkovitz, Yehuda / Zager, Yaniv / Lavy, Ron

The Israel Medical Association journal : IMAJ

2022 Volume 24, Issue 10, Page(s) 677–678

MeSH term(s)	Humans ; Appendix/surgery ; Gastrointestinal Stromal Tumors/diagnosis ; Gastrointestinal Stromal Tumors/surgery ; Gastrointestinal Stromal Tumors/pathology
Language	English
Publishing date	2022-10-30
Publishing country	Israel
Document type	Journal Article
ZDB-ID	2008291-5
ISSN	1565-1088 ; 0021-2180
ISSN	1565-1088 ; 0021-2180
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Article ; Online: Iron sucrose ('RBT-3') activates the hepatic and renal HAMP1 gene, evoking renal hepcidin loading and resistance to cisplatin nephrotoxicity.

Zager, Richard A / Johnson, Ali C M / Therapeutics, Renibus

Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association

2021 Volume 36, Issue 3, Page(s) 465–474

Abstract: Background: Iron sucrose (FeS) administration induces a state of renal preconditioning, protecting against selected forms of acute kidney injury (AKI). Recent evidence suggests that recombinant hepcidin also mitigates acute renal damage. Hence the goals ...

Abstract	Background: Iron sucrose (FeS) administration induces a state of renal preconditioning, protecting against selected forms of acute kidney injury (AKI). Recent evidence suggests that recombinant hepcidin also mitigates acute renal damage. Hence the goals of this study were to determine whether a new proprietary FeS formulation ('RBT-3') can acutely activate the hepcidin (HAMP1) gene in humans, raising plasma and renal hepcidin concentrations; assess whether the kidney participates in this posited RBT-3-hepcidin generation response; test whether RBT-3 can mitigate a clinically relevant AKI model (experimental cisplatin toxicity) and explore whether mechanisms in addition to hepcidin generation are operative in RBT-3's cytoprotective effects. Methods: Healthy human volunteers (n = 9) and subjects with Stages 3-4 CKD (n = 9) received 120, 240 or 360 mg of RBT-3 (intravenously over 2 h). Plasma and urine samples were collected and assayed for hepcidin levels (0-72 h post-RBT-3 injection). In complementary mouse experiments, RBT-3 effects on hepatic versus renal hepcidin (HAMP1) messenger RNA (mRNA) and protein levels were compared. RBT-3's impact on the mouse Nrf2 pathway and on experimental cisplatin nephrotoxicity was assessed. Direct effects of exogenous hepcidin on in vivo and in vitro (HK-2 cells) cisplatin toxicity were also tested. Results: RBT-3 induced rapid, dose-dependent and comparable plasma hepcidin increases in both healthy volunteers and chronic kidney disease subjects (∼15 times baseline within 24 h). Human kidney hepcidin exposure was confirmed by 4-fold urinary hepcidin increases. RBT-3 up-regulated mouse hepcidin mRNA, but much more so in kidney (>25 times) versus liver (∼2 times). RBT-3 also activated kidney Nrf2 [increased Nrf2 nuclear binding; increased Nrf2-responsive gene mRNAs: heme oxygenase-1, sulfiredoxin-1, glutamate-cysteine ligase catalytic subunit and NAD(P)H quinone dehydrogenase 1]. RBT-3 preconditioning (18 h time lapse) markedly attenuated experimental cisplatin nephrotoxicity (∼50% blood urea nitrogen/creatinine decrements), in part by reducing renal cisplatin uptake by 40%. Exogenous hepcidin (without RBT-3) treatment conferred protection against mild in vivo (but not in vitro) cisplatin toxicity. Conclusions: RBT-3 acutely and dramatically up-regulates cytoprotective hepcidin production, increasing renal hepcidin levels. However, additional cytoprotective mechanisms are activated by RBT-3 (e.g. Nrf2 activation; reduced cisplatin uptake). Thus RBT-3-induced preconditioning likely confers renal resistance to cisplatin via an interplay of multiple cytoprotective activities.
MeSH term(s)	Aged ; Animals ; Antineoplastic Agents/toxicity ; Case-Control Studies ; Cisplatin/toxicity ; Drug Resistance/drug effects ; Female ; Ferric Oxide, Saccharated/pharmacology ; Gene Expression Regulation/drug effects ; Hepcidins/genetics ; Hepcidins/metabolism ; Humans ; Kidney/drug effects ; Kidney/metabolism ; Liver/drug effects ; Liver/metabolism ; Male ; Mice ; Middle Aged ; Renal Insufficiency, Chronic/drug therapy ; Renal Insufficiency, Chronic/metabolism ; Renal Insufficiency, Chronic/pathology
Chemical Substances	Antineoplastic Agents ; Hepcidins ; Ferric Oxide, Saccharated (FZ7NYF5N8L) ; Cisplatin (Q20Q21Q62J)
Language	English
Publishing date	2021-02-05
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	90594-x
ISSN	1460-2385 ; 0931-0509
ISSN (online)	1460-2385
ISSN	0931-0509
DOI	10.1093/ndt/gfaa348
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Article ; Online: Isolated hyperthermic perfusions for cutaneous melanoma in-transit metastasis of the limb and uveal melanoma metastasis to the liver.

Huibers, Anne / DePalo, Danielle K / Perez, Matthew C / Zager, Jonathan S / Olofsson Bagge, Roger

Clinical & experimental metastasis

2023

Abstract: Patients with cutaneous melanoma can develop in-transit metastases (ITM), most often localized to limbs. For patients with uveal melanoma that develop metastatic disease, the overall majority develop isolated liver metastases. For these types of ... ...

Abstract	Patients with cutaneous melanoma can develop in-transit metastases (ITM), most often localized to limbs. For patients with uveal melanoma that develop metastatic disease, the overall majority develop isolated liver metastases. For these types of metastases, regional cancer therapies have evolved as effective treatments. Isolated limb perfusion (ILP), isolated limb infusion (ILI), isolated hepatic perfusion (IHP) and percutaneous hepatic perfusion (PHP) achieve a high local concentration of chemotherapy with minimal systemic exposure. This review discusses the mechanism and available literature on locoregional treatment modalities in the era of modern immunotherapy.
Language	English
Publishing date	2023-10-16
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	604952-7
ISSN	1573-7276 ; 0262-0898
ISSN (online)	1573-7276
ISSN	0262-0898
DOI	10.1007/s10585-023-10234-6
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Article ; Online: Oncolytic intralesional therapy for metastatic melanoma.

DePalo, Danielle K / Perez, Matthew C / Huibers, Anne / Olofsson Bagge, Roger / Zager, Jonathan S

Clinical & experimental metastasis

2023

Abstract: In-transit metastasis (ITM) develop in approximately 1 in 10 patients with melanoma and the disease course can vary widely. Surgical resection is the gold-standard treatment; however, ITM are often surgically unresectable due to size, distribution, and/ ... ...

Abstract	In-transit metastasis (ITM) develop in approximately 1 in 10 patients with melanoma and the disease course can vary widely. Surgical resection is the gold-standard treatment; however, ITM are often surgically unresectable due to size, distribution, and/or anatomic involvement. Oncolytic viral therapies are one category of non-surgical treatment options available for ITM. They induce tumor cell lysis and systemic anti-tumor activity through selective infection of tumor cells by naturally occurring or genetically modified factors. While there are numerous oncolytic viral therapies in various stages of development for the treatment of ITM, this discussion focuses on the mechanism and available literature for the two most established herpes virus-based therapies.
Language	English
Publishing date	2023-08-09
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	604952-7
ISSN	1573-7276 ; 0262-0898
ISSN (online)	1573-7276
ISSN	0262-0898
DOI	10.1007/s10585-023-10228-4
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Article ; Online: Isolated Limb Infusion for Limb-Threatening, Unresectable Sarcoma

Danielle K. DePalo / Jonathan S. Zager

Journal of Clinical Medicine, Vol 12, Iss 4036, p

Past Progress, Current Applications, and Future Directions

2023 Volume 4036

Abstract: Treatment of soft tissue sarcomas (STSs) is complicated by disease heterogeneity. Further, it has not benefitted much from the recent therapeutic advances in other soft tissue malignancies. Surgical resection remains the gold standard in resectable ... ...

Abstract	Treatment of soft tissue sarcomas (STSs) is complicated by disease heterogeneity. Further, it has not benefitted much from the recent therapeutic advances in other soft tissue malignancies. Surgical resection remains the gold standard in resectable disease, but unresectable, locally advanced STS requires alternative and multimodal approaches. Isolated limb infusion (ILI) provides regional chemotherapy to extremity STS and offers the potential for limb salvage. Despite being in use for nearly 3 decades, there is limited literature on ILI in STS. This review provides an overview of patient eligibility, the procedure, significant publications in this field, and opportunities for further progress.
Keywords	isolated limb infusion ; regional chemotherapy ; sarcoma ; soft tissue sarcoma ; Medicine ; R
Language	English
Publishing date	2023-06-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Neutrophil to Lymphocyte Ratio in Patients Who Received Neoadjuvant Treatment before Gastrectomy.

Zager, Yaniv / Goldes, Yuri / Assaf, Dan / Zilka, Nadav / Anteby, Roi / Nevo, Yehonatan / Barda, Liran / Nevler, Avinoam

The Israel Medical Association journal : IMAJ

2023 Volume 25, Issue 5, Page(s) 336–340

Abstract: ... NLR was associated with greater rate of local complication (r=0.268, P < 0.01). The rate of major ...

Abstract	Background: The neutrophil to lymphocyte ratio (NLR) has demonstrated prognostic value in various malignant conditions, including gastric adenocarcinoma. However, chemotherapy may affect NLR. Objectives: To evaluate the prognostic value of NLR as an accessory decision-making tool in terms of operating patients after neoadjuvant chemotherapy in patients with resectable gastric cancer. Methods: We collected oncologic, perioperative, and survival data of patients with gastric adenocarcinoma who underwent curative intent gastrectomy and D2 lymphadenectomy between 2009 and 2016. The NLR was calculated from preoperative laboratory tests and classified as high (> 4) and low (≤ 4). The t-test, chi-square, Kaplan-Meier analysis, and Cox multivariate regression models were used to assess associations of clinical, histologic, and hematological variables with survival. Results: For 124 patients the median follow-up was 23 months (range 1-88). High NLR was associated with greater rate of local complication (r=0.268, P < 0.01). The rate of major complications (Clavien-Dindo ≥ 3) was higher in the high NLR group (28% vs. 9%, P = 0.022). Among the 53 patients who received neoadjuvant chemotherapy, those with low NLR had significantly improved disease-free survival (DFS) (49.7 vs. 27.7 months, P = 0.025). Low NLR was not significantly associated with overall survival (mean survival, 51.2 vs. 42.3 months, P = 0.19). Multivariate regression identified NLR group (P = 0.013), male gender (P = 0.04), and body mass index (P = 0.026) as independently associated with DFS. Conclusions: Among gastric cancer patients planned for curative intent surgery who underwent neoadjuvant chemotherapy, NLR may have prognostic value, particularly regarding DFS and postoperative complications.
MeSH term(s)	Humans ; Male ; Neoadjuvant Therapy ; Stomach Neoplasms/surgery ; Neutrophils/pathology ; Lymphocytes ; Prognosis ; Adenocarcinoma/pathology ; Gastrectomy/adverse effects ; Retrospective Studies ; Lymphocyte Count
Language	English
Publishing date	2023-05-28
Publishing country	Israel
Document type	Journal Article
ZDB-ID	2008291-5
ISSN	1565-1088 ; 0021-2180
ISSN	1565-1088 ; 0021-2180
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Article ; Online: Plasma and urinary p21: potential biomarkers of AKI and renal aging.

Johnson, Ali C / Zager, Richard A

American journal of physiology. Renal physiology

2018 Volume 315, Issue 5, Page(s) F1329–F1335

Abstract: ... this process? Mice were subjected to either ischemia-reperfusion (I/R) or nephotoxic (maleate) AKI. Renal ... Renal I/R also activated p21 gene expression in extrarenal organs (heart, brain), consistent ... which correlated ( r, 0.83) with rising plasma p21 concentrations. We concluded that 1) during AKI, renal p21 ...

Abstract	p21 is upregulated in renal tubules in response to acute kidney injury ( AKI). and localizes in the nucleus, where it induces cell cycle arrest (CCA). These events can mitigate early injury but can also facilitate the onset of the degenerative cell senescence/"aging" process. Hence, we asked the following: 1) can AKI-induced p21 upregulation be gauged by plasma and/or urinary p21 assay; 2) might p21 serve as an AKI/CCA biomarker; and 3) does p21 accumulate during normal renal aging, and might plasma p21 reflect this process? Mice were subjected to either ischemia-reperfusion (I/R) or nephotoxic (maleate) AKI. Renal cortical p21 expression (protein, mRNA) was assessed 2-18 h later and contrasted with plasma/urine p21 concentrations (ELISA). p21 mRNA/protein levels were also measured in aging mice (2, 12, 24 mo). AKI induced marked, progressive, increases in renal cortical p21 mRNA and protein levels. These changes were marked by acute (within 2-4 h) and profound increases (up to 200×) in both plasma and urine p21 concentrations. Renal I/R also activated p21 gene expression in extrarenal organs (heart, brain), consistent with so-called "organ cross talk". p21 efflux from damaged cells was confirmed with studies of hypoxia-injured, isolated proximal tubules. Aging was associated with progressive renal cortical p21 expression, which correlated ( r, 0.83) with rising plasma p21 concentrations. We concluded that 1) during AKI, renal p21 increases can be gauged by either plasma or urine p21 assay, serving as potentially useful AKI/CCA biomarkers; 2) AKI can activate p21 in extrarenal organs; and 3) plasma p21 levels may provide an index of the renal/systemic aging process.
MeSH term(s)	Acute Kidney Injury/blood ; Acute Kidney Injury/genetics ; Acute Kidney Injury/pathology ; Acute Kidney Injury/urine ; Age Factors ; Aging/blood ; Aging/genetics ; Aging/urine ; Animals ; Biomarkers/blood ; Biomarkers/urine ; Brain/metabolism ; Cell Death ; Cyclin-Dependent Kinase Inhibitor p21/blood ; Cyclin-Dependent Kinase Inhibitor p21/genetics ; Cyclin-Dependent Kinase Inhibitor p21/urine ; Disease Models, Animal ; Kidney/metabolism ; Kidney/pathology ; Male ; Mice ; Myocardium/metabolism ; Reperfusion Injury/blood ; Reperfusion Injury/genetics ; Reperfusion Injury/urine ; Time Factors ; Up-Regulation
Chemical Substances	Biomarkers ; Cdkn1a protein, mouse ; Cyclin-Dependent Kinase Inhibitor p21
Language	English
Publishing date	2018-08-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	603837-2
ISSN	1522-1466 ; 0363-6127
ISSN (online)	1522-1466
ISSN	0363-6127
DOI	10.1152/ajprenal.00328.2018
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Article ; Online: Surgical outcomes of minimally invasive trephine surgery for pilonidal sinus disease with and without laser therapy: a comparative study.

Horesh, N / Maman, R / Zager, Y / Anteby, R / Weksler, Y / Carter, D / Nachmany, I / Ram, E

Techniques in coloproctology

2023 Volume 28, Issue 1, Page(s) 13

Abstract: Background: Over the last decades, novel therapeutic options have emerged for the surgical treatment of pilonidal sinus disease (PSD). The aim of this study was to evaluate the outcomes of trephine/pit excision surgery with or without laser therapy in ... ...

Abstract	Background: Over the last decades, novel therapeutic options have emerged for the surgical treatment of pilonidal sinus disease (PSD). The aim of this study was to evaluate the outcomes of trephine/pit excision surgery with or without laser therapy in patients with PSD. Methods: A retrospective cohort study was conducted at a large tertiary medical center, including all adult patients with PNS who underwent trephine surgery with/without laser therapy between 2016 and 2021[AUTHORS TO INSERT MONTH]. Propensity score matching was used to address confounding factors, and the primary outcome was the 1-year recurrence rate. Results: The study included 221 patients with PSD, with a mean age of 23.73 years (87.7% male). In the unmatched cohort (130 trephine surgery alone, 91 trephine surgery + laser therapy), significant differences were observed in mean age (23 vs. 25 years; p < 0.01)[AUTHROS TO USE MEDIAN PLUS RANGE OR ADD SD] and surgeons' experience (p = 0.014). Propensity score matching was applied to overcome confounding factors, resulting in a matched cohort including 73 patients in each group. The addition of laser therapy demonstrated a significantly lower recurrence rate (8.2% vs. 32.9%; p < 0.001) compared to pit excision without laser therapy. Logistic regression analysis showed that the addition of laser was significantly associated with a lower risk for recurrence (OR 0.23; 95% CI 0.089-0.633; p < 0.01). Conclusion: The incorporation of laser therapy along with trephine/pit excision surgery significantly reduces the recurrence rate in patients with PNS. Further prospective studies are needed to confirm our findings.
MeSH term(s)	Adult ; Humans ; Male ; Young Adult ; Female ; Treatment Outcome ; Pilonidal Sinus/surgery ; Retrospective Studies ; Neoplasm Recurrence, Local/surgery ; Laser Therapy ; Recurrence
Language	English
Publishing date	2023-12-13
Publishing country	Italy
Document type	Journal Article
ZDB-ID	2083309-X
ISSN	1128-045X ; 1123-6337
ISSN (online)	1128-045X
ISSN	1123-6337
DOI	10.1007/s10151-023-02897-w
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Zs.A 5842: Show issues

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Article: Tumors of the brachial plexus region: A 15-year experience with emphasis on motor and pain outcomes and literature review.

Pisapia, Jared M / Adeclat, Giscard / Roberts, Sanford / Li, Yun R / Ali, Zarina / Heuer, Gregory G / Zager, Eric L

Surgical neurology international

2023 Volume 14, Page(s) 162

Abstract: Background: Brachial plexus region tumors are rare. In this study, we reviewed our experience with resection of tumors involving or adjacent to the brachial plexus to identify patterns in presentation and outcome.: Methods: We report a retrospective ... ...

Abstract	Background: Brachial plexus region tumors are rare. In this study, we reviewed our experience with resection of tumors involving or adjacent to the brachial plexus to identify patterns in presentation and outcome. Methods: We report a retrospective case series of brachial plexus tumors operated on by a single surgeon at a single institution over 15 years. Outcome data were recorded from the most recent follow-up office visit. Findings were compared to a prior internal series and comparable series in the literature. Results: From 2001 to 2016, 103 consecutive brachial plexus tumors in 98 patients met inclusion criteria. Ninety percent of patients presented with a palpable mass, and 81% had deficits in sensation, motor function, or both. Mean follow-up time was 10 months. Serious complications were infrequent. For patients with a preoperative motor deficit, the rate of postoperative motor decline was 10%. For patients without a preoperative motor deficit, the rate of postoperative motor decline was 35%, which decreased to 27% at 6 months. There were no differences in motor outcome based on extent of resection, tumor pathology, or age. Conclusion: We present one of the largest recent series of tumors of the brachial plexus region. Although the rate of worsened postoperative motor function was higher in those without preoperative weakness, the motor deficit improves over time and is no worse than antigravity strength in the majority of cases. Our findings help guide patient counseling in regard to postoperative motor function.
Language	English
Publishing date	2023-05-05
Publishing country	United States
Document type	Journal Article
ISSN	2229-5097
ISSN	2229-5097
DOI	10.25259/SNI_163_2023
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Article ; Online: The value of CA125 in predicting acute complicated colonic diverticulitis.

Zager, Yaniv / Khalilieh, Saed / Mansour, Aiham / Cohen, Karin / Nadler, Roy / Anteby, Roi / Ram, Edward / Horesh, Nir / Nachmany, Ido / Gutman, Mordechai / Berger, Yaniv

International journal of colorectal disease

2023 Volume 38, Issue 1, Page(s) 182

Abstract: ... intra-abdominal abscess (n = 24), CA125 levels were correlated with the size of the abscess (Spearman's r = 0.46, p = 0.02 ...

Abstract	Background: CA125 is a widely used serum marker for epithelial ovarian cancer which levels may also rise in benign conditions involving peritoneal irritation. We aimed to determine if serum CA125 levels can predict disease severity in patients presenting with acute diverticulitis. Methods: We conducted a single-center prospective observational study, analyzing CA125 serum levels in patients who presented to the emergency department with computerized tomography-proven acute left-sided colonic diverticulitis. Univariate, multivariate, and receiver operating characteristic (ROC) analyses were used to correlate CA125 serum levels at time of initial presentation with the primary outcome (complicated diverticulitis) and secondary clinical outcomes (need for urgent intervention, length of hospital stay (LOS) and readmission rates). Results: One hundred and fifty-one patients were enrolled between January 2018 and July 2020 (66.9% females, median age 61 years). Twenty-five patients (16.5%) presented with complicated diverticulitis. CA125 levels were significantly higher among patients with complicated (median: 16 (7-159) u/ml) vs. uncomplicated (8 (3-39) u/ml) diverticulitis (p < 0.001) and also correlated with the Hinchey severity class (p < 0.001). Higher CA125 levels upon admission were associated with a longer LOS and a greater chance to undergo invasive procedure during the hospitalization. In patients with a measurable intra-abdominal abscess (n = 24), CA125 levels were correlated with the size of the abscess (Spearman's r = 0.46, p = 0.02). On ROC analysis to predict complicated diverticulitis, the area under the curve (AUC) for CA125 (AUC = 0.82) was bigger than for the leukocyte count (AUC = 0.53), body temperature (AUC = 0.59), and neutrophil-lymphocyte ratio (AUC = 0.70) - all p values < 0.05. On multivariate analysis of factors available at presentation, CA125 was found to be the only independent predictor of complicated diverticulitis (OR 1.12 (95% CI 1.06-1.19), p < 0.001). Conclusions: The results from this feasibility study suggest that CA125 may accurately discriminate between simple and complicated diverticulitis, meriting further prospective investigation.
MeSH term(s)	Female ; Humans ; Middle Aged ; Male ; Diverticulitis, Colonic/complications ; Diverticulitis, Colonic/diagnosis ; Diverticulitis ; Abdominal Abscess ; Abscess
Language	English
Publishing date	2023-06-30
Publishing country	Germany
Document type	Observational Study ; Journal Article
ZDB-ID	84975-3
ISSN	1432-1262 ; 0179-1958
ISSN (online)	1432-1262
ISSN	0179-1958
DOI	10.1007/s00384-023-04478-7
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