Non-response Group Research Articles

Association study of genetic polymorphisms in GABRD with treatment response and dose in methadone maintenance treatment.

Aim: This study determined if gene variants in the GABA receptor delta subunit (GABRD) are associated with treatment response and dose in methadone maintenance treatment (MMT) for heroin addiction. Materials & methods:Atotal of286 MMT patients were recruited and divided into response and nonresponse groups based on retention time in therapy. A total of 177 responders were classified into low dose and high dose subgroups according to the stabilized methadone dose. Four (single nucleotide polymorphisms)SNPs (rs13303344, rs4481796, rs2376805 andrs2229110) in GABRD were genotyped using the TaqMan SNP assay. Logistic regression was used to assess the genetic effects of the SNPs in MMT. Results: No significant associations were observed between the SNPs and treatment response or dose, except the frequency of haplotype ACGC atthe four SNPs significantly differed between responders and nonresponders. Conclusion: The results indicated that GABRD variants may play a small role in modulating methadone treatment response.

Differences in responsiveness of intratympanic steroid injection for intractable vertigo in Meniere's disease

ObjectivesThe efficacy of intratympanic steroid (ITS) injection for intractable Meniere's disease has been reported; however, its differences in responsiveness are not fully understood. This study investigated the clinical characteristics of patients who responded to ITS injection treatment. MethodsThis retrospective study included 32 patients with Meniere's disease who were unable to control frequent vertigo attacks despite conservative treatment for at least 3 months. They received an intratympanic injection of dexamethasone (3.3 mg/mL) in the affected side at least three times. We measured hearing threshold, subjective symptom scores, cervical and ocular vestibular evoked myogenic potential (cVEMP and oVEMP), and performed glycerol and bithermal caloric tests. ResultsSatisfactory control of vertigo for 1 year after the first round of injection was found in 18 patients (56.3%; the response group). However, the injections failed to control vertigo in the other 14 patients (43.8%; the non-response group), and they were then treated with middle ear micropressure therapy. The response group showed improvement in low-frequency hearing, whereas hearing acuity did not change in the non-response group. Significantly reduced amplitude of cVEMP on the affected side was found in 62.5% of patients in the response group; however, no patients in the non-response group showed reduced amplitude of cVEMP. ConclusionsITS injection significantly improved the subjective symptoms for intractable Meniere's disease; however, the long-term effects were heterogeneous. Our results suggest that reduced amplitude in cVEMP is associated with the effectiveness of ITS injection treatment.

Camrelizumab plus chemotherapy as neoadjuvant therapy for resectable, locally advanced esophageal squamous cell carcinoma (NIC-ESCC2019): A multicenter, open-label, single-arm, phase 2 study.

4028 Background: Despite multidisciplinary therapies, prognosis of pts with resectable esophageal squamous cell carcinoma (ESCC) remains poor. Combining PD-1 blockade to neoadjuvant chemotherapy might be a feasible and effective strategy. Camrelizumab (an anti-PD-1 antibody) was approved for advanced or metastatic ESCC in the second-line setting and showed improved anti-tumor activity and survival benefit when combined with chemotherapy in multiple advanced tumors. Methods: In this NIC-ESCC2019 phase 2 study, histologically or cytologically confirmed ESCC pts (stage II-IVA) were enrolled to receive two cycles of neoadjuvant chemoimmunotherapy (NIC) with camrelizumab (200 mg on day 1) plus nab-paclitaxel (260 mg/m² in total on day 1 and day 8) and cisplatin (75 mg/m² in total on days 1-3) of each 21-day cycle, followed by esophagectomy. The primary endpoint was complete pathologic response (CPR) rate in the primary tumor. Besides, we also explored the relationship between the tumor genomic profile or primary-tumor microenvironment and the pathological response. Results: Between Jan 17, 2020 and Dec 8, 2020, 56 pts were enrolled. 51 pts underwent surgical resection, and all had complete tumor resection. CPR was achieved in 18 (35.3%; 95% CI, 21.7%-48.9%) pts; 12 (23.5%) pts had major pathologic response (MPR), and 21 (41.2%) had incomplete pathological response (IPR). Of note, 16 (31.4%) pts achieved CPR in both primary tumor and lymph nodes. The objective response rate was 66.7% (95% CI, 40.0-70.4). No in-hospital mortality occurred. The most common treatment-related adverse events (TRAEs) were decreased WBC (20 [36%] of 56 pts), vomiting (19 [34%]), and alopecia (18 [32%]). Grade 3 TRAEs only occurred in 6 (11%) pts, and there were no grade 4 or 5 TRAEs. The most common immune-related AEs included grade 1-2 rash maculo-papular (7 [13%]) and reactive cutaneous capillary endothelial proliferation (5 [9%]). Presence of mutations in CREBBP and KMT2D at treatment-naïve time-point was correlated with non-response group (IPR and stable disease) (CREBBP, p = 0.046; KMT2D, p = 0.047). Among the immune populations, CD8+, CD8+PD-1+ and CD8+PD-L1+ T cells increased significantly after two doses of NIC, especially in the CPR+MPR group (CD8+, p = 0.013; CD8+PD-1+, p < 0.001; CD8+PD-L1+, p = 0.068). Conclusions: The addition of camrelizumab to neoadjuvant chemotherapy in ESCC demonstrated promising efficacy with acceptable toxicity, supporting the further investigation in a randomized phase 3 clinical trial. Clinical trial information: NCT04225364. [Table: see text]

Immune Microenvironment in Langerhans Cell Histiocytosis: Potential Prognostic Indicators.

In this study, the immune microenvironment in Langerhans cell histiocytosis (LCH) was characterized to determine if immune indices are predictive of severity. Serum samples from 54 treatment-naïve patients were analyzed quantitatively for inflammatory cytokines and immunoglobulins before and after the induction of chemotherapy. The initial serum sIL-2R, TNF-α, and IL-10 of untreated LCH patients with risk organ involvement (RO+) were significantly higher than those with single-system (SS) involvement. LCH patients with hematologic involvement exhibited a significantly higher sIL-2R, TNF-α, IL-10, and IL-1β expression, as compared to the group without involvement. sIL-2R, TNF-α, and IL-10 were increased in patients with liver or spleen involvement. Th cells have decreased in the liver+ and spleen+ group, and Ts cells were significantly decreased in non-response group after induction chemotherapy. The serum level of immune indices represents, to some extent, the severity of the disease. Pertinent laboratory inspections can be used to improve risk stratification and guide immunotherapy.

Baseline serum exosome-derived miRNAs predict HBeAg seroconversion in chronic hepatitis B patients treated with peginterferon.

This study aimed to explore the value of baseline serum exosome-derived miRNAs for predicting HBeAg seroconversion in chronic hepatitis B (CHB) patients treated with peginterferon (Peg-IFN). A total of 120 treatment-naïve HBeAg-positive CHB patients who received Peg-IFN therapy (48 weeks) were enrolled. Next-generation sequencing was performed to screen the serum exosomal miRNAs that were associated with Peg-IFN treatment outcome, and qRT-PCR was used to validate them. The area under the receiver operating characteristic curve (AUROC) was used to evaluate the predictive efficacy of biomarkers. Thirty-three patients (27.5%) achieved HBeAg seroconversion (response group), and 87 patients (72.5%) did not achieve HBeAg seroconversion (nonresponse group). In the identification cohort, 40 serum exosome-derived miRNAs were differentially expressed between the response group (four patients) and the nonresponse group (four patients). In the confirmation cohort, the expression levels of serum exosomal miR-194-5p (p < .001) and miR-22-3p (p < .001) were significantly downregulated in the response group (29 patients) compared to the nonresponse group (83 patients). Multivariate analysis identified baseline serum exosomal miR-194-5p, miR-22-3p, alanine aminotransferase (ALT), and HBV DNA as independent predictors of HBeAg seroconversion (all p < .05). The AUROCs of serum exosomal miRNAs (0.77 and 0.75 for miR-194-5p and miR-22-3p, respectively) were higher than that of ALT (0.70) and HBV DNA (0.69). The combination of exosomal miR-194-5p and miR-22-3p further improved the predictive performance with an AUROC of 0.82. Baseline serum exosomal miR-194-5p and miR-22-3p may serve as novel biomarkers to predict HBeAg seroconversion in CHB patients treated with Peg-IFN.

Association of macrophage inhibitory factor -1 polymorphisms with antiviral efficacy of type 1b chronic hepatitis C

The expression of macrophage inhibitory factor-1 (MIC-1) increases in patients with chronic hepatitis C (CHC), but whether MIC-1 level and its polymorphism affect the antiviral efficacy of CHC has not yet been reported. The present study aimed to investigate the association between MIC-1 polymorphism and antiviral efficacy in patients with CHC genotype 1b (CHC 1b). A total of 171 patients with CHC1b were recruited. The polymorphisms of rs1059369 and rs1059519 in MIC-1 were detected by DNA sequencing. All patients received a standard dose of polyethylene glycol interferon + ribavirin (PR regimen), and divided into response, nonresponse, sustained virological response (SVR), and non-sustained virological response (NSVR) groups based on HCV RNA levels. The genotype distribution of the two single nucleotide polymorphisms (SNPs) did not differ between the response and nonresponse groups, SVR and non-SVR groups. However, the level of MIC-1 was positively correlated with ALT, AST, PIIINP, CIV, and HCV RNA (P < 0.05). Compared to before treatment, the level of MIC-1 in plasma was significantly decrease in the response group but not in the non-responsive group. Our results suggest that the level of MIC-1 in CHC1b is correlated with liver cell injury, liver fibrosis index, and viral load. However, the polymorphism of rs1059369 and rs1059519 may have negligible impact in expression of MIC-1 and efficacy of antiviral therapy in CHC patient.

Relationship between Changes of Lymphocyte Subsets and Early Hematologic Response in Immunosuppressive Therapy of Severe Aplastic Anemia Patients

To explore the relationship between the change of lymphocyte subsets before and after immunosuppressive therapy (IST) with disease severity of severe aplastic anemia (SAA) and hematologic response to IST. The clinical data of 94 patients with SAA/VSAA treated by r-ATG and CsA in our hospital from December 2009 to October 2011 was analyzed retrospectively. Among them, 26 patients who had sequential data of lymphocyte subsets and cytokines before and after treatment were enrolled. The relationship between lymphocyte subsets, cytokine level before IST and disease severity, as well as the relationship between changes if lymphocyte subsets, changes of cytokine and the HR after IST for 6 months was analyzed. There were no statistical differences in the ratio and absolute count of lymphocyte, the ratio and absolute count of each lymphocyte subsets, including CD3+T cells, CD3+CD4+T cells, CD3+CD8+T cells, CD3-CD16+1CD56+NK cells, and CD19+B cells, and the level of cytokines, such as IL-1, IL-2, IL-4, IL-6 and TNF-α before IST between SAA and VSAA groups. Also, there were no statistical difference in the levels of above-motional parameter at 3 and 6 months after IST. The ratio and absolute count of Lym, absolute count of CD3+T cells, absolute count of B cells and IL-2 level in response group after IST for 3 and 6 months was significant lower than those before IST. However, only ratio of Lym showed significant decrease after IST for 3 and 6 months in non-response group. After IST for 3 months, the absolute count of CD3+T and CD4+T cells in response group was significant higher than those in non-response group. The hematopoietic recovery and early hematologic remission may be affected by the intensity of immune suppression reflected from the changes of lymphocyte subsets and the immune reconstruction reflected from the recovery of lymphocyte subsets. The immune reconstruction is most significant within 3 months after IST.

Cyclosporine modulates neutrophil functions via the SIRT6-HIF-1α-glycolysis axis to alleviate severe ulcerative colitis.

BackgroundCyclosporine A (CsA) is routinely used to treat patients with steroid‐refractory acute severe ulcerative colitis (ASUC). Here, we studied the underlying mechanisms of CsA‐mediated alleviation in ASUC patients.MethodsNeutrophil functions including expression of cytokines, apoptosis, and migration were measured by qRT‐PCR, flow cytometry, and Transwell assay. Dynamic changes of glycolysis and tricarboxylic acid (TCA) cycle were measured by a Seahorse extracellular flux analyzer. Gene differences were determined and verified by RNA sequencing, qRT‐PCR, and Western blotting. Small interfering RNA and inhibitors were used to knock down Sirtuin 6 (SIRT6) in HL‐60 cells and block expression of SIRT6, hypoxia‐inducible factor‐1α (HIF‐1α), and pyruvate dehydrogenase lipoamide kinase isozyme 4 (PDK4) in neutrophils.ResultsWe found that HIF‐1α expression and glycolysis significantly increased, while the release of IL‐8, myeloperoxidase (MPO) and reactive oxygen species (ROS), the apoptosis, and ability of migration markedly decreased in neutrophils of ASUC patients who responded to CsA (Response group) compared with those who did not respond to CsA (Nonresponse group). We also observed that CsA‐induced functional alternation of neutrophils was initiated through suppressing SIRT6 expression, which is responsible for expression of the downstream signaling molecules (e.g., HIF‐1α, PFKFB3) and PDK4 ubiquitination, leading to fueling neutrophil glycolysis and TCA cycle. Furthermore, blockage of SIRT6 signaling demonstrated to be the same functional changes as CsA to decrease the migration of neutrophils.ConclusionsThe data reveal a novel mechanism of CsA in alleviating ASUC by promoting neutrophil HIF‐1α expression and restricting excessive neutrophil activation in a SIRT6−HIF‐1α−glycolysis axis, suggesting SIRT6 as a candidate target for maintaining mucosal homeostasis and treating intestinal inflammation.

Deep learning-assisted magnetic resonance imaging prediction of tumor response to chemotherapy in patients with colorectal liver metastases.

Accurate evaluation of tumor response to preoperative chemotherapy is crucial for assigning appropriate patients with colorectal liver metastases (CRLM) to surgery or conservative therapy. However, there is no well-recognized method for predicting pathological response before surgery. Our study constructed and validated a deep learning algorithm using prechemotherapy and postchemotherapy magnetic resonance imaging (MRI) to predict pathological response in CRLM. CRLM patients from center one who had ≤5 lesions and were scheduled to receive preoperative chemotherapy followed by liver resection between January 2013 and November 2016, were included prospectively and chronologically divided into a training cohort (80% of patients) and a testing cohort (20% of patients). Patients from center two were included January 2017 and December 2018 as an external validation cohort. MRI-based models were constructed to discriminate according to pathology tumor regression grade (TRG) between the response (TRG1/2) and nonresponse (TRG3/4/5) groups at the lesion level. From center one, 155 patients (328 lesions) were included; chronologically, 101 (264 lesions) in the training cohort and 54 (64 lesions) in the testing cohort. The model achieved better accuracy (0.875 vs 0.578) and AUC (0.849 vs 0.615) than RECIST for discriminating response; it also distinguished the survival outcomes after hepatectomy better than the RECIST criteria. Evaluations of the external validation cohort (25 patients, 61 lesions) also showed good ability with an AUC of 0.833. In conclusion, the MRI-based deep learning model provided accurate prediction of pathological tumor response to preoperative chemotherapy in patients with CRLM and may inform individualized treatment.

Clinicopathological Profile of Low-Grade B Cell Non-Hodgkin Lymphoma in Tertiary Health Care in West Java Indonesia

Background: Low-grade B cell Non-Hodgkin lymphomas (NHL) are a group of lymphomas that are predominantly indolent and make up approximately 50% of all malignant lymphomas. Initial therapy for low-grade B cell LNH has an overall response rate of between 85-94% and a refractory rate of 6-10%. Few reports have been published regarding the clinicopathological characteristics of non-Hodgkin lymphoma cases, especially low-grade B cell types. This research aims to determine the clinicopathological profile of low-grade B cell type non-Hodgkin lymphoma cases.&#x0D; Method: This research is a descriptive study using cross-sectional methods. The sample consisted of 40 low-grade B cell type NHL cases from January 2015 to June 2020 at Hasan Sadikin Hospital, Bandung. Clinicopathological data, including age, sex, location of the tumor (nodal or extranodal), stage, B symptoms, and response to therapy, were taken from the patients’ medical records. Data were categorized into 2 groups based on response to initial therapy.&#x0D; Results and Discussion: Of the 40 cases diagnosed with low-grade B cell type NHL, 55% responded to initial therapy. From the non-response group, 61.1% were stage II and 72.2% exhibited B symptoms. There were no significant differences in age, sex, tumor location (nodal or extranodal), stage, or B symptoms in the response and non-response groups.&#x0D; Conclusion: In this study, 45% of patients with low-grade B cell type NHL did not respond to initial therapy. There was no statistically significant difference in the clinicopathological profiles of the response and non-response groups to initial therapy in cases of low-grade B cell type NHL.&#x0D; Keywords: Non-Hodgkin Lymphoma, low-grade B cell lymphoma, therapy response, clinicopathological

Hydrogen in Patients With Corticosteroid-Refractory/Dependent Chronic Graft-Versus-Host-Disease: A Single-Arm, Multicenter, Open-Label, Phase 2 Trial.

Chronic graft-versus-host-disease (cGVHD) is the leading cause of late non-relapse mortality after allogeneic hematopoietic stem cell transplantation(HSCT). There is no standard therapy for patients refractory or dependent to corticosteroid treatment. We hypothesized that hydrogen may exert therapeutic effects on cGVHD patients with few side effects. A prospective open-label phase 2 study of hydrogen was conducted. Patients received hydrogen-rich water 4ml/kg orally three times a day. Responses were graded in the skin, mouth, Gastrointestinal(GI), liver, eyes, lungs and joints and fascia every 3 months. A total of 24 patients (median age 27) were enrolled. Of the 24 patients, 18 (75%; 95% CI, 55.1% to 88%) had an objective response. No significant toxicity was observed. The estimated 4-year overall survival rate was 74.7%(95% CI, 54.9%–94.5%). The survival time was significantly prolonged in the response group. The survival rate at 4 years in the response group is significantly higher than the nonresponse group (86.6% vs 0%; p= 0.000132). Hydrogen showed great efficacy on cGVHD patients and long-term administration of hydrogen was not associated with significant toxic effects. The trial was registered at www.ClinicalTrials.Gov, NCT02918188.

Treatment Response to Gabapentin in Neuropathic Ocular Pain Associated with Dry Eye.

Purpose: To investigate the response to gabapentin treatment in patients with dry eye (DE) accompanied by features of neuropathic ocular pain (NOP), and to analyze the differences between clinical manifestations of the groups according to treatment response. Methods: We retrospectively reviewed the records of 35 patients with DE accompanied by NOP features and obtained information on their medical history and previous ocular history. The patients underwent clinical examinations of the tear film, ocular surface, and meibomian gland and completed the Ocular Pain Assessment Survey (OPAS). One month after treatment with topical eye drops, add-on of gabapentin treatment was determined according to the Wong–Baker FACES Pain Rating Scale (WBFPS). A reduction of 2 points or more on the WBFPS was considered a positive treatment response. Enrolled patients were divided into three groups according to the treatment response: topical treatment response group (group 1, n = 11); gabapentin response group (group 2, n = 13); and gabapentin non-response group (group 3, n = 11). The medical history, clinical parameters, and OPAS scores were compared between groups. Results: The incidence of systemic comorbidities was higher in group 2 than in other groups. The corneal staining scores were lower in groups 2 and 3 than in group 1. Among the treatment response groups, group 2 showed improvements in OPAS scores of ocular pain severity, pain other than eyes, and quality of life, while group 1 showed improved OPAS scores of ocular pain severity and ocular associated factors. Group 2 exhibited lower scores of pains aggravated by mechanical and chemical stimuli than group 3. Conclusions: Gabapentin could be effective in patients who have systemic comorbidity and less pain evoked by mechanical and chemical stimuli for the treatment of DE patients with NOP, which is refractory to topical treatment.

Endoscopic ultrasound-guided radiofrequency ablation of pancreatic neuroendocrine tumors: a systematic review of the literature.

Background and study aims Surgery is the mainstay therapy for pancreatic neuroendocrine tumors (P-NETs), but it is associated with significant adverse events (AEs). In recent years, endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) has been described for treating P-NETs. We performed a systematic literature review aimed at exploring the feasibility, effectiveness, and safety of EUS-RFA in treatment of P-NETs. Methods The literature review was performed in PubMed/MEDLINE, EMBASE, and SCOPUS to identify all case reports of EUS-RFA for treatment of P-NETs. Results Sixyt-one patients (males 49.2 %, mean age 64.5 years) and 73 tumors (mean size 16 mm, insulinomas 30.1 %) treated with EUS-RFA were included from 12 studies. The overall effectiveness of EUS-RFA was 96 % (75 % – 100 %) without differences between functional vs. non-functional P-NETs ( P = 0.3) and without relevant issues about safety (mild AEs 13.7 %). While tumor location was not predictive for incomplete/non-response to EUS-RFA, greater tumor dimensions predicted treatment failure (21.8 ± 4.71 mm in the non-response group vs 15.07 ± 7.34 mm in the response group, P = 0.048). At ROC analysis, a P-NET size cut-off value ≤18 mm predicted response to treatment, with a sensitivity of 80 % (95 % CI 28.4 % – 99.5 %), a specificity of 78.6 % (95 % CI 63.2 % – 89.7 %), a positive predictive value of 97.1 % (95 % CI 84.7 % – 99.9 %) and a negative predictive value of 30.8 % (95 % CI 9.1 % – 61.4 %), with an area under the curve of 0.81 (95 % CI 0.67 – 0.95). Conclusions EUS-RFA is safe and effective for treating P-NETs. It may be reasonable to consider EUS-RFA for small P-NETs, irrespective of the functional status.

The Association Between the Level of Leukemic Stem Cells and Treatment Response Among Chronic Myeloid Leukemia Patients Treated with Imatinib Mesylate

Background: The failure of imatinib therapy in patients with chronic myeloid leukemia (CML) is associated with the presence of leukemic stem cell (LSC), and the altered LSC level was reported to occur earlier in the progression of CML. Objective: The study aimed to assess the association between the level of LSC and treatment response among CML patients treated with imatinib mesylate. Methods: A cross-sectional study was conducted in Saiful Anwar Hospital. All participants were divided into two groups, response and non-response group. To assess the level of LSC, flow cytometry was conducted conforming with BD Bioscience. The association and effect estimates were determined using multiple logistic regression. Results and Discussion: A total of 29 response and non-response CML patients treated with imatinib therapy were recruited for our study. After six months of imatinib therapy, we found that elevated levels of leukocytes, thrombocytes, basophils, and blast cells were associated with treatment failure among CML patients treated with imatinib. Moreover, we also found that the LSC level was observed significantly higher in the non-response group compared to the response group among CML patients treated with imatinib. Conclusion: Our study reveals that the elevated level of LSC is considered as an important factor to predict the failure of imatinib therapy among CML patients.

Effects of Inflammatory Disease on Clinical Progression and Treatment of Ischiogluteal Bursitis: A Retrospective Observational Study.

Introduction:The symptoms of Ischiogluteal Bursitis (IGB) are often nonspecific and atypical, and its diagnosis is more challenging. Moreover, it is difficult to predict cases of chronic progression or poor treatment response. Therefore, the aim of this study was to investigate the clinical course of IGB patients and identify factors that are predictive of failure of conservative treatment.Materials and Methods:Our study consisted of IGB patients diagnosed between 2010 March and 2016 December who had been followed-up for at least one year. Structured questionnaires and medical records were reviewed to analyse demographic characteristics, lifestyle patterns, blood tests, and imaging studies. We categorized the cases into two groups based on the response to conservative treatment and the need for surgical intervention.Results:The most common initial chief symptoms were buttock pains in 24 patients (37.5%). Physical examinations showed the tenderness of ischial tuberosity area in 59 (92.2%) patients, but no specific findings were confirmed in 5 patients (7.8%). 51 patients (79.7%) responded well to the conservative management, 11 patients (17.2%) needed injection, and 2 patients (3.1%) had surgical treatment performed due to continuous recurrence. There was no difference in demographic and blood lab data between the two groups. However, the incidence of inflammatory diseases (response group: 10.3% vs non-response group: 66.7%, p=0.004) was significantly different between the two groups.Conclusion:The diagnosis of IGB can be missed due to variations in clinical symptoms, and cautions should be exercised in patients with inflammatory diseases as conservative treatment is less effective in them, leading to chronic progression of IGB.

Digital Twins and the Emerging Science of Self: Implications for Digital Health Experience Design and “Small” Data

The technology currently available for quantifying various biometric, behavioral, emotional, cognitive and psychological aspects of daily life has become increasingly diverse, accurate and accessible. Continued improvements are ongoing. These burgeoning technologies can and will profoundly alter the way lifestyle, health, wellness and chronic diseases are managed in the future. For those pursuing the potential of such digital technologies in the creation of compelling and effective connected healthcare experiences, a number of new concepts have surfaced. We have taken these concepts (many of which originate in engineering) and extended them to be incorporated into managing health risk and health conditions via a blended digital health experience. For example, the advent of mobile technology for health has given rise to concepts such as ecological momentary assessment (EMA) and ecological momentary intervention (EMI) that assess the person’s (digital twin) status and delivers interventions as needed when needed. For such concepts to be fully realized the experience design of mHealth program(s) (aka connected care) should and now can actually guide the end user through a series of self-experiments directed by data-driven feedback from a version of their digital twin. As treatment development and testing moves towards the precision of individual differences inherent in every person and every treatment response (or non-response) group data and more recent big data approaches for generating new knowledge offer limited help to end-users (including practitioners) for helping individuals evaluate their own digital twin generated data and change over time under different conditions. This is the renaissance of N-of-1 or individual science. N-of-1 evaluation creates the opportunity to evaluate each individual uniquely. The rigor and logic of N-of-1 designs have been well articulated and expanded upon for over a half-century. For the clinician, this revitalized form of scientific and behavioral interaction evaluation can help validate or reject the impact a given treatment has for a given patient with increased efficiency and accuracy. Further, N-of-1 can incorporate biological (genomic), behavioral, psychological and digital health data such that users themselves can begin to evaluate the relationships of their own treatment response patterns and the contingencies that impact them. Thus, emerges the self-scientist.

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

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.

Pretreatment Apparent Diffusion Coefficient as a Predictor of Response to Transcatheter Arterial Chemoembolization Immediately Combined with Radiofrequency Ablation for Treatment of Solitary Large Hepatocellular Carcinoma.

PurposeTo evaluate whether the pretreatment apparent diffusion coefficient (ADC) measured with diffusion weighted imaging (DWI) of tumor can be used as an imaging biomarker for predicting prognosis in solitary large hepatocellular carcinomas (HCCs) treated with transcatheter arterial chemoembolization (TACE) immediately combined with radiofrequency ablation (RFA).Patients and MethodsIn this single institution retrospective study, 40 solitary large HCCs that underwent treatment with TACE immediately combined with RFA were analyzed. All patients underwent abdominal dynamic contrast-enhanced magnetic resonance imaging within one month before treatment with DWI, and ADC values in the lesions were measured by two independent radiologists. Associations among patients’ preoperative ADC values and objective response (OR), progression-free survival (PFS) and overall survival (OS) were examined. Survival curves were drawn with the Kaplan–Meier method, and differences were determined with the Log rank test. The Cox proportional-hazards model was used for univariate and multivariate analyses of PFS and OS.ResultsForty solitary large HCCs (mean 9.54 cm, range 5.04–16.06 cm) were successfully treated with TACE in immediate combination with RFA (OR 75%). The ADC values were significantly higher in the response group than the non-response group (1.51±0.32×10−3 mm2/s vs 1.09±0.17×10−3 mm2/s; P<0.001). As predicted on the basis of the ADC values, the optimal cutoff value for the efficacy of TACE combined with RFA was 1.32×10−3 mm2/s, with a predictive sensitivity of 0.63 and a specificity of 1.00. Patients with high ADC had longer PFS than those with low ADC (14.9 months vs 5.3 months; P<0.001) and had significantly longer survival rates (22.6 months vs 12.1 months; P=0.004).ConclusionPreoperative ADC values <1.32×10−3 mm2/s are an independent predictor of poorer prognosis in patients with solitary large HCCs who have undergone TACE immediately combined with RFA.

Dynamic contrast-enhanced magnetic resonance imaging biomarkers predict chemotherapeutic responses and survival in primary central-nervous-system lymphoma.

To evaluate the utility of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in predicting the response of chemotherapy and clinical outcomes in primary central-nervous-system lymphoma (PCNSL) patients. DCE-MRI in 56 patients enrolled in a prospective study was performed at baseline and 30 days after treatment from 2016 to 2019. Multivariate logistic regression analyses were performed to assess risk factors for tumor responses. The predictive values of related parameters derived from DCE were analyzed via receiver operating characteristic (ROC) curve analysis. To evaluate prognostic factors, the Kaplan-Meier survival analysis with log-rank tests and Cox regression tests were analyzed. Ktrans and Ve were higher in the non-response group than in the response group (p < 0.05). The Ktrans and the percentage of Ktrans decreased after 30 days of treatment were independent predictors of chemotherapy responses (p = 0.034 and p = 0.019). ROC analysis indicated that the cut-off point of Ktrans for predicting chemotherapeutic responses was 0.353 min-1 (AUC, 0.941; 95% CI, 0.87-1; p < 0.001) and percentage of Ktrans decreased after 30 days of treatment was 15.2% (AUC, 0.858; 95% CI, 0.742-0.970; p < 0.001). The greater decrease in Ktrans correlated with a longer progression-free survival (PFS) (χ2 = 13.203, p < 0.001). The higher Ktrans was an independent predictor for shorter PFS (hazard ratio, 10.182; 95% CI, 2.510-41.300; p = 0.001). Ktrans and Ktrans change measured by DCE-MRI were reliable biomarkers for predicting chemotherapy responses in PCNSL patients. • Baseline Ktrans and greater decrease in Ktrans can predict chemotherapeutic efficacy. • DCE-MRI provides quantitative parameters reflecting the tumor microenvironment. • Targeted treatment therapy can be given with more evidence in the future.

Pretreatment MRI-Derived Radiomics May Evaluate the Response of Different Induction Chemotherapy Regimens in Locally advanced Nasopharyngeal Carcinoma

To evaluate and compare the performance of radiomics in predicting induction chemotherapy response treated with two different regimens in patients with advanced nasopharyngeal carcinoma. A total of 265 patients with pathologically confirmed locally advanced nasopharyngeal carcinoma (stage II-IV), including 115 treated with gemcitabine plus cisplatin (GP group) and 150 treated with docetaxel plus cisplatin (TP group) were retrospectively enrolled. Radiomics features were extracted from the volume of interest delineated in multi-MR sequences on a 3T scanner. After random stratified grouping (training and validation cohorts) and logistic regression based on selected features, the association between the radiomics signature and the early response to induction chemotherapy were established for GP and TP regiments, respectively. Clinical factors showed no significant difference between the response and non-response groups for the GP and TP regiments (all p > 0.05). The accuracy of the radiomics signature consisting of selected features from the joint T1, T2, and T1C in the GP group (0.852 in the training cohort vs. 0.853 in the validation cohort) was significantly higher than that in the TP group (0.774 vs 0.727). The overall performance of the GP model was steady, with efficiency to distinguish responders from nonresponders with an AUC reaching 0.907 (95% confidence interval [CI] [0.843-0.970]) in the training cohort and 0.886 (95% CI [0.772-0.998]) in the validation cohort, while leveling at 0.800 (95% CI [0.712-0.888]) in the training cohort and 0.863 (95% CI [0.758-0.967]) in the validation cohort in the TP group. Pretreatment MR radiomics signature can better predict the early response to IC in the GP regimen than the TP regimen, which may be helpful to guide IC management.