Analysis of HLA-G expression in renal tissue in lupus nephritis: a pilot study

Background The study aimed to investigate whether HLA-G antigen is expressed in the kidneys of patients affected by lupus nephritis (LN) and whether its detection in renal biopsies could be adopted as a marker of treatment response and prognosis. Methods Thirty renal biopsies from patients with LN were selected and analyzed through immunohistochemistry. Laboratory and clinical data were retrospectively collected at baseline, 6 and 12 months and at the latest clinical appointment. A number of patients (63.3%) were treated with rituximab (RTX) +/− methylprednisolone in the induction phase. The expression of HLA-G in glomeruli, tubules and infiltrating cells was examined and compared between lupus patients who achieved either complete or partial renal response and those who did not respond to treatment. Results HLA-G staining was observed in the glomeruli of 20 of 30 samples from patients with LN. The expression of the antigen was detected in podocytes, along glomerular capillary walls, on parietal glomerular epithelial cells and within the juxtaglomerular apparatus. Seventy per cent of patients whose glomeruli expressed HLA-G achieved partial or complete response at 6 months and 75% at the latest available follow up compared with 30% and 40%, respectively, of those who did not show any expression. The pattern of staining in tubules and infiltrating cells was highly variable precluding any clinical correlation. Conclusion This study demonstrates that HLA-G is expressed in renal tissue in LN. Our retrospective data suggest that its expression could correlate with response to treatment.

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Urine TWEAK level as a biomarker for early response to treatment in active lupus nephritis: a prospective multicentre study

Lupus Science & Medicine ◽

10.1136/lupus-2018-000298 ◽

2019 ◽

Vol 6 (1) ◽

pp. e000298 ◽

Cited By ~ 5

Author(s):

Thitima Benjachat Suttichet ◽

Wonngarm Kittanamongkolchai ◽

Chutipha Phromjeen ◽

Sirirat Anutrakulchai ◽

Thanachai Panaput ◽

...

Keyword(s):

Lupus Nephritis ◽

Treatment Response ◽

Induction Therapy ◽

Characteristic Curve ◽

Predictive Performance ◽

Complete Response ◽

Early Response ◽

Response To Treatment ◽

Urine Protein ◽

Spot Urine

BackgroundTNF-like weak inducer of apoptosis (TWEAK) is a proinflammatory molecule that plays a key role in active inflammation of lupus nephritis (LN). Urine TWEAK (uTWEAK) levels were found to be associated with renal disease activity among patients with LN. Here, we determined whether serial measurements of uTWEAK during induction therapy could predict treatment response or not.MethodsSpot urine samples were collected from patients with biopsy-proven active LN at time of flare, and 3 and 6 months after flare to assess the uTWEAK levels. All patients received standard immunosuppressive therapy and treatment response was evaluated at 6 months. The performance of uTWEAK as a predictor for treatment response was compared with clinically used biomarkers for patients with LN.ResultsAmong 110 patients with LN, there were 29% complete responders (CR), 34% partial responders (PR) and 37% non-responders (NR). On average, uTWEAK level was consistently low in CR, trended down by 3 months in PR and persistently elevated in NR. uTWEAK levels at month 3 were able to predict complete response at month 6 (OR adjusted for age, sex and creatinine=0.34 [95% CI 0.15 to 0.80], the area under the receiver operating characteristic curve [ROC-AUC]=0.68, p=0.02). The optimal threshold for uTWEAK level at month 3 was 0.46 pg/mgCr, discriminating complete response with 70% sensitivity and 63% specificity. Combining uTWEAK and urine protein at month 3 improved predictive performance for complete response at 6 months (ROC-AUC 0.83, p<0.001).ConclusionsIn addition to urine protein, uTWEAK level at 3 months after flare can improve the accuracy in predicting complete response at 6 months of induction therapy.

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Systemic therapy in primary angiosarcoma of the spleen

Rare Tumors ◽

10.4081/rt.2012.e55 ◽

2012 ◽

Vol 4 (4) ◽

pp. 178-180 ◽

Cited By ~ 11

Author(s):

Bruna Pellini Ferreira ◽

Eve T. Rodler ◽

Elizabeth T. Loggers ◽

Seth M. Pollack ◽

Robin L. Jones

Keyword(s):

Metastatic Disease ◽

Systemic Therapy ◽

Cancer Care ◽

Complete Response ◽

Response To Treatment ◽

Rare Neoplasm ◽

Primary Angiosarcoma ◽

Number Of Patients ◽

Splenic Angiosarcoma ◽

Third Line

Primary splenic angiosarcoma is a very rare neoplasm with a high propensity for metastatic disease and poor prognosis. There is a paucity of literature concerning this specific sarcoma subtype and the role of systemic therapy is not well defined. A retrospective review of the prospectively maintained University of Washington/Seattle Cancer Care Alliance Sarcoma Unit database was performed to identify patients with splenic angiosarcoma treated between 2007 and 2012. In total there were 19 patients with angiosarcoma treated at the Seattle Cancer Care Alliance from 2007 to 2012. The number of patients with splenic angiosarcoma was 2 (11%). The first patient was a woman aged 57 years who was referred with metastatic splenic angiosarcoma to the liver, post-splenectomy. She was treated with 4 cycles of weekly paclitaxel prior to metastatic resection and 4 cycles of the same drug in an adjuvant scenario, achieving a pathological complete response to treatment. She is alive and on third-line systemic therapy. The second patient was a male patient aged 30 years who presented with metastatic high-grade splenic angiosarcoma and was treated with 3 lines of systemic therapy, including doxorubicin, paclitaxel and gemcitabine+docetaxel, but developed a gastrointestinal metastasis with subsequent gastrointestinal bleeding. Splenic angiosarcoma is a very rare neoplasm. Surgery remains the mainstay of management for localized disease. Paclitaxel administered weekly proved to be well-tolerated and resulted in a good radiological response in one of our patients, enabling resection of metastatic disease. Durable clinical benefit can be achieved in metastatic splenic angiosarcoma with multi modality management.

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Contribution of “complete response to treatment” to survival in patients with unresectable metastatic colorectal cancer: A retrospective analysis

PLoS ONE ◽

10.1371/journal.pone.0259622 ◽

2021 ◽

Vol 16 (11) ◽

pp. e0259622

Author(s):

Gulcan Bulut ◽

Merve Guner Oytun ◽

Elvina Almuradova ◽

Mustafa Harman ◽

Ruchan Uslu ◽

...

Keyword(s):

Colorectal Cancer ◽

Liver Metastasis ◽

Bone Metastasis ◽

Metastatic Colorectal Cancer ◽

Systemic Treatment ◽

Complete Response ◽

Response To Treatment ◽

Primary Surgery ◽

Number Of Patients ◽

Unresectable Metastatic Colorectal Cancer

Background The aim of the study is to reveal the contribution of complete response (CR) to treatment to overall survival (OS) in patients with unresectable metastatic colorectal cancer. In addition, to evaluate progression-free survival (PFS) in patients who attained CR to treatment and to examine the clinicopathologic features of the patient group with CR. Methods This article is a retrospective chart review. Patients diagnosed with metastatic colorectal cancer were divided into two groups. The systemic treatment was compared with the patients who received a full response according to the Response Evaluation Criteria in Solid Tumors (RECIST1.1) and those who did not attain CR (progression partial response and stable response) in terms of both PFS and OS data, and the effect of attaining CR to treatment on prognosis was evaluated. Results A total of 222 patients were included in the study. 202 of 222 patients could be evaluated in terms of complete response. All data from their files were tabulated and analyzed retrospectively. The mean age of diagnosis of the study group was 60.13 ± 12.52 years. The total number of patients who attained CR to treatment was 31 (15.3%); 171 (84.6%) patients did not attain CR. Patients who had a CR had longer median PFS times than patients who did not have a CR (15.2 vs. 7.4 months, P<0.001). Patients who had CR had longer median survival times than patients who did not have a CR (39.2 vs. 16.9 months, P<0.001). In subgroup patients who underwent primary surgery, the number of patients who attained CR was statistically higher compared with the number of patients who did not attain CR (p<0.001). Complete response was less common in the presence of liver metastasis and bone metastasis (p = 0.041 and p = 0.046, respectively), had a negative prognostic effect. In other words, 89.1% of patients with liver metastasis, 100.0% of patients with bone metastasis, and 88.7% of those who died did not have a CR to the treatment. According to multivariate analysis, CR to treatment, primary surgery, first-line chemotherapy (combination compared with fluoropyrimidine), and no bone metastasis were found to be predictors for OS. Conclusion Providing CR with systemic treatment in patients with unresectable metastatic colorectal cancer (mCRC) contributes to prognosis. The primary resection in our secondary acquisitions from the study, the number of metastatic regions and the combination therapy regimens also contributed to the prognosis.

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Urinary Neutrophil Gelatinase-Associated Lipocalin as a Novel Predictor in Treatment of Active Lupus Nephritis

QJM ◽

10.1093/qjmed/hcab100.119 ◽

2021 ◽

Vol 114 (Supplement_1) ◽

Author(s):

Gamal E Mady ◽

Sahar M Shawky ◽

Walid A Bichari ◽

Mohamed S Hassan ◽

Ahmed M Tawfik ◽

...

Keyword(s):

Lupus Nephritis ◽

Renal Disease ◽

Induction Therapy ◽

Lupus Erythematosus ◽

Complete Response ◽

Response To Treatment ◽

Class Iii ◽

Neutrophil Gelatinase Associated Lipocalin ◽

Response Groups ◽

Neutrophil Gelatinase

Abstract Introduction Lupus nephritis (LN) affects almost two-thirds of Systemic lupus erythematosus (SLE) patients. Despite initial aggressive therapy, up to 25% of patients with LN will progress to end stage renal disease (ESRD). Conventional serum markers for LN lack the sensitivity of an ideal biomarker. Urinary Neutrophil gelatinase-associated lipocalin (UNGAL) is an excellent biomarker for early diagnosis of acute kidney injury and predicting renal outcomes. Objectives To measure UNGAL among LN patients correlating its levels with renal disease activity to investigate its predictive performance in response to induction therapy. Patients and Methods 40 SLE patients with biopsy-proven LN, class III, IV, or V were randomly selected. The study was conducted in internal medicine department and Outpatient clinic in Ain Shams University Hospitals on and completed after six months. UNGAL was measured at baseline and after complete induction therapy. Results In LN patients at baseline; mean UNGAL levels of complete response, partial response, and no response groups were 14.48 ±2.99 ng/ml, 34.49 ±4.09, and 62.07 ±14.44 ng/ml respectively. Based on ROC curve, we found better performance of baseline UNGAL to discriminate complete response group from partial and non-response groups to predict response to induction, outperforming conventional biomarkers. The area under the curve was 0.943 (92.31% sensitivity, 88.89% specificity), and the best cut-off level was 26.5 ng/ml. Conclusion UNGAL performed better than conventional biomarkers in predicting response to treatment of active LN.

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Value of Urinary Neutrophil Gelatinase-Associated Lipocalin versus Conventional Biomarkers in Predicting Response to Treatment of Active Lupus Nephritis

International Journal of Nephrology ◽

10.1155/2020/8855614 ◽

2020 ◽

Vol 2020 ◽

pp. 1-8

Author(s):

Mohamed Abd El-Mohsen ◽

Ahmed Tawfik ◽

Walid Bichari ◽

Sahar Shawky ◽

Gamal Mady ◽

...

Keyword(s):

Lupus Nephritis ◽

Induction Therapy ◽

Lupus Erythematosus ◽

Complete Response ◽

Response To Treatment ◽

Class Iii ◽

University Hospitals ◽

Neutrophil Gelatinase Associated Lipocalin ◽

The Mean ◽

Neutrophil Gelatinase

Introduction. Lupus nephritis (LN) affects almost two-thirds of systemic lupus erythematosus (SLE) patients. Despite initial aggressive therapy, up to 25% of patients with LN will progress to permanent renal damage. Conventional serum markers for LN lack the sensitivity of an ideal biomarker. Urinary neutrophil gelatinase-associated lipocalin (UNGAL) is an excellent biomarker for early diagnosis of acute kidney injury and predicting renal outcomes. Objective. To measure UNGAL among LN patients to correlate its levels with renal disease activity and to investigate its predictive performance in response to induction therapy. Patients and Methods. 40 SLE patients with biopsy-proven LN class III, IV, or V were randomly selected. The study was conducted in the internal medicine department and outpatient clinic in Ain Shams University Hospitals and completed after six months. UNGAL was measured at baseline, three-month follow-up, and after complete induction therapy. Results. In LN patients at baseline, the mean serum creatinine was 2.57 ± 0.96 mg/dL and the mean UNGAL was 33.50 ± 18.34 ng/dL. Mean UNGAL levels of complete response, partial response, and nonresponse groups were 14.48 ± 2.99 ng/mL, 34.49 ± 4.09 ng/mL, and 62.07 ± 14.44 ng/mL, respectively. Based on the ROC curve, we found a better performance of baseline UNGAL to discriminate the complete response group from partial and nonresponse groups to predict response to induction, outperforming conventional biomarkers. The area under the curve was 0.943, and the best cutoff level was 26.5 ng/mL (92.31% sensitivity and 88.89% specificity). Conclusion. UNGAL performed better than conventional biomarkers in predicting response to treatment of active LN.

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Peripheral Blood B Cell Depletion after Rituximab and Complete Response in Lupus Nephritis

Clinical Journal of the American Society of Nephrology ◽

10.2215/cjn.01070118 ◽

2018 ◽

Vol 13 (10) ◽

pp. 1502-1509 ◽

Cited By ~ 21

Author(s):

Liliana Michelle Gomez Mendez ◽

Matthew D. Cascino ◽

Jay Garg ◽

Tamiko R. Katsumoto ◽

Paul Brakeman ◽

...

Keyword(s):

Lupus Nephritis ◽

B Cell ◽

Peripheral Blood ◽

Complete Response ◽

Normal Serum ◽

Interquartile Range ◽

Cell Depletion ◽

Response To Treatment ◽

Inadequate Response ◽

B Cell Depletion

Background and objectivesIncomplete peripheral blood B cell depletion after rituximab in lupus nephritis might correlate with inability to reduce tubulointerstitial lymphoid aggregates in the kidney, which together could be responsible for inadequate response to treatment. We utilized data from the Lupus Nephritis Assessment with Rituximab (LUNAR) study to characterize the variability of peripheral blood B cell depletion after rituximab and assess its association with complete response in patients with lupus nephritis.Design, setting, participants, & measurementsWe analyzed 68 participants treated with rituximab. Peripheral blood B cell depletion was defined as 0 cells/µl, termed “complete peripheral depletion,” assessed over 78 weeks. Logistic regression was used to estimate the association between characteristics of complete peripheral depletion and complete response (defined as urine protein-to-creatinine ratio <0.5 mg/mg, and normal serum creatinine or an increase in creatinine <15%, if normal at baseline), assessed at week 78.ResultsA total of 53 (78%) participants achieved complete peripheral depletion (0 cells/µl) in a median time of 182 days (interquartile range, 80–339).The median duration of complete peripheral depletion was 71 days (interquartile range, 14–158). Twenty-five (47%) participants with complete peripheral depletion achieved complete response, compared with two (13%) without. Complete peripheral depletion was associated with complete response (unadjusted odds ratio [OR], 5.8; 95% confidence interval [95% CI], 1.2 to 28; P=0.03). Longer time to achieving complete peripheral depletion was associated with a lower likelihood of complete response (unadjusted OR, 0.89; 95% CI, 0.81 to 0.98; P=0.02). Complete peripheral depletion lasting >71 days (the median) was associated with complete response (unadjusted OR, 4.1; 95% CI, 1.5 to 11; P=0.008).ConclusionsThere was substantial variability in peripheral blood B cell depletion in patients with lupus nephritis treated with rituximab from the LUNAR trial. Achievement of complete peripheral depletion, as well as the rapidity and duration of complete peripheral depletion, were associated with complete response at week 78.PodcastThis article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2018_09_06_CJASNPodcast_18_10_.mp3

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Progressive Muscle Relaxation in Hyperemesis Gravidarum

Journal of SAFOG with DVD ◽

10.5005/jp-journals-10006-1118 ◽

2011 ◽

Vol 3 (1) ◽

pp. 28-32 ◽

Cited By ~ 3

Author(s):

Madhuri Vaidya ◽

Sushil Gawande ◽

Rahul Tadke ◽

Vivek Kirpekar ◽

Sudhir Bhave

Keyword(s):

Hyperemesis Gravidarum ◽

Muscle Relaxation ◽

Complete Response ◽

Early Response ◽

Progressive Muscle Relaxation ◽

Response To Treatment ◽

Control Group ◽

Global Improvement ◽

Number Of Patients ◽

Experimental Group

ABSTRACT Aims To assess the role of progressive muscle relaxation in the management of hyperemesis gravidarum. Methods This is a prospective, randomized, observer blind and comparative study. Around 30 pregnant women admitted for the treatment of hyperemesis gravidarum were enrolled and randomized into experimental and control groups. Each group was of 15 patients. Experimental group patients received pharmacotherapy with daily progressive muscle relaxation for 2 weeks, while patients in control group received only pharmacotherapy. Results (1) Significantly high number of patients required three or more drugs in control group as compared to experimental group, (2) experimental group patients achieved complete response within 2.73 days ± SD, while control group patients achieved complete response within 4 days ± SD, (3) none of the patients in experimental group had recurrence within 2 weeks of observation period, while 13% patients in control group had recurrence after complete response, (4) on clinical global improvement scale, patients in experimental group achieved better improvement. Conclusions Progressive muscle relaxation is effective in hyperemesis gravidarum and when combined with antiemetics, it reduces the number of antiemetics required to treat hyperemesis gravidarum. Patients also show early response to treatment, less recurrence and better improvement when combined with antiemetics.

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Correlation Between Serological Makers and Immunofluorescence Deposits i n Kidney Tissue of Patients with Lupus Nephritis

International Journal of Drug Delivery Technology ◽

10.25258/ijddt.9.2.22 ◽

2019 ◽

Vol 9 (02) ◽

Author(s):

Haider S Al-Hadad ◽

Aqeel Abbas Matrood ◽

Maha Abdalrasool Almukhtar ◽

Haider Jabur Kehiosh ◽

Riyadh Muhi Al-Saegh

Keyword(s):

Lupus Nephritis ◽

Lupus Erythematosus ◽

Kidney Biopsy ◽

Pearson Correlation ◽

Standard Procedure ◽

Kidney Tissue ◽

P Value ◽

American College Of Rheumatology ◽

Immune Deposits ◽

Number Of Patients

Background: Systemic lupus erythematosus (SLE) is an autoimmune disease. Few biomarkers for SLE have been validated and widely accepted for the laboratory follow-up of inflammatory activity. In SLE patients, with lupus nephritis (LN), complement activation leads to fluctuation of serum C3 and C4 that are frequently used as clinicalm biomarker of disease activity in SLE. Patients and Methods: In this study the number of patients were 37, seven patients were excluded for incomplete data collection, 28 were females ,2 were males. The duration of the study is two years from 2015 to 2017. Patients were considered to have SLE and LN according to American College of Rheumatology (ACR) criteria, and International Society of Nephrology/ Renal Pathology Society (ISN/RPS). All patients were evaluated withm clinical presentation, laboratory investigations. Our patients underwent kidney biopsy according to standard procedure by Kerstin Amann, and their tissue specimens were studied in the laboratory with light microscope (LM) and immunofluorescence microscope reagents. The relationship between the serological markers and immunofluorescence deposits in kidney biopsy of all patients were studied using the statistical analysis of Pearson correlation and single table student's T test. A P value 0.05 was considered statistically significant. Results: The granular pattern of IF deposits was present in all LN patients, and in more than two third of patients these IF deposits presented in glomerular, tubular, and mesangium sites. While less than one third of patients had IF deposits in the mesangium only. There was no statistically significant correlation between serum ANA, anti-dsDNA, and IF deposits of different types. There was significant correlation between serum C3 and C4 hypocomplementemia and IgG immune deposits in kidney biopsy, and there was significant relationship between serum C3 hypocomplementemia and full house immunofluorescence (FHIF) deposits inm kidney biopsy.Conclusions:Immunofluorescence deposits is mainly granular pattern in LN patients. There was no significant association between serum ANA, anti-dsDNA, and immune deposits in kidney tissue. Immunofluorescence deposits of IgG type correlates significantly with serum C3 and C4 hypocomplemetemia, and these immune deposits in association with low complement levels correlates with LN flare. There was significant correlation between C3 hypocomplementemia and FHIF.

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Predictive Factors Affecting the Success of Nephrectomy for the Treatment of Nephrogenic Hypertension: Multicenter Study

Urologia Internationalis ◽

10.1159/000515652 ◽

2021 ◽

pp. 1-6

Author(s):

Ediz Vuruskan ◽

Hakan Ercil ◽

Umut Unal ◽

Ergun Alma ◽

Hakan Anil ◽

...

Keyword(s):

Metabolic Syndrome ◽

Partial Response ◽

Medical Treatment ◽

Predictive Factors ◽

Treatment Success ◽

Complete Response ◽

Response To Treatment ◽

Factors Affecting ◽

Success Of Treatment ◽

Functioning Kidney

Introduction: The aim of our study is to evaluate the predictive factors affecting the success of treatment with nephrectomy in patients with poorly functioning kidney and nephrogenic hypertension. Methods: Data for patients who underwent nephrectomy with a diagnosis of nephrogenic hypertension in 3 centers between May 2010 and January 2020 were analyzed. In the postoperative period, if the blood pressure (BP) was below 140/90 mm Hg without medical treatment, it was accepted as complete response; if the arterial BP was below 140/90 mm Hg with medical treatment or less medication, it was accepted as partial response; and if BP did not decrease to normal values, it was accepted as unresponsive. Demographic characteristics, duration of hypertension, preoperative and postoperative BP values, and presence of metabolic syndrome were statistically evaluated. Results: Our study consisted of 91 patients with a mean preoperative hypertension duration of 23.3 ± 12.1 months. Among patients, 42 (46.2%) had complete response, 18 (19.8%) had partial response, and 31 (34.0%) had no response. Preoperative systolic and diastolic BP values were not effective on treatment success (p = 0.071, p = 0.973, respectively), but the increase in age and hypertension duration (p = 0.030 and p < 0.001, respectively) and the presence of metabolic syndrome (p = 0.002) significantly decreased the complete response rates. Conclusions: Preoperative hypertension duration, advanced age, and presence of metabolic syndrome are predictive factors affecting the response to treatment in patients who undergo nephrectomy due to nephrogenic hypertension.

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Myopic foveal detachment associated with pachychoroid characteristics

BMC Ophthalmology ◽

10.1186/s12886-021-02040-z ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Yong Kyun Shin ◽

Sun Hyup Han ◽

Se Woong Kang ◽

Sang Jin Kim ◽

A Young Kim

Keyword(s):

Vascular Endothelial Growth Factor ◽

Multimodal Imaging ◽

High Myopia ◽

Complete Response ◽

Response To Treatment ◽

Vascular Endothelial ◽

Foveal Detachment ◽

Endothelial Growth Factor ◽

Choroidal Vascular Hyperpermeability

Abstract Purpose To describe myopic nontractional foveal detachment associated with pachychoroid diseases. Methods This retrospective study included 15 myopic eyes which had nontractional serous foveal detachment. The eyes were divided into myopic central serous chorioretinopathy (CSC) group (n = 8) and a myopic pachychoroid neovascularization (PNV) group (n = 7) according to the presence of type 1 choroidal neovascularization on multimodal imaging. The findings of multimodal imaging and treatment response were described. Results In myopic CSC group, pachychoroid features such as pachyvessels, choroidal vascular hyperpermeability and punctate hyperfluorescent spots were noted in 8 eyes (100%), 8 eyes (100%), 5 eyes (62.5%) respectively. The above features were noted in 7 eyes (100%), 5 eyes (83.3%), 5 eyes (83.3%), respectively, in the myopic PNV group. Five of 8 eyes in myopic CSC and all 7 eyes received treatment including anti-vascular endothelial growth factor injection and/or photodynamic therapy. However, only five eyes had a complete response. Conclusions The pachychoroid phenotype may coexist with high myopia and lead to myopic nontractional serous foveal detachment. Our series suggest that the response to treatment for these conditions would be limited.

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