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Dec 2017 DOI 10.14302/issn.2766-8630.jrnm-17-1770
Y. Moawad EmadCorresponding author
Independent researcher graduated from department of engineering, Ain Shams University
The aims of this study are to investigate the variation in the mechanical behaviour of the primary cancer from cancer relapse, and measuring the therapeutic resistance acquired by cancer relapse. A431-cultured cells were irradiated for 7 months until 85 Gy. Then, a selected single cell was left to grow as stable A431-R cell line. 106 cells of A431 cells and 106 of A431-R cells suspended in 100 μL of medium were injected into subcutaneous tissues on the right thigh of athymic mice to generate tumor xenografts models of primary cancer (A431-P) and cancer relapse (A431-R). Radiotherapy of a low-dose of 30Gy was applied on xenoimplanted tumors after one week from inoculation. A mock process was performed on untreated groups of mice for controls. Tumor size was monitored starting from inoculation and tumor growth was measured along 42 days. Rates of mitosis and apoptosis and the histologic grade (HG) that characterize the tumor response were determined as described in earlier studies. Alterations induced on tumor HG in the treated models were 100% identical to the energy of the applied doses. The differences in response energy between cancer relapse and primary cancer irrespectively of the treatment (untreated vs. treated) or origin of the cells (A431-P vs. A431-R) in all phases of tumor responses (growth, shrinkage or regrowth) were 100% identical to the total differences in the administered regimens applied on those groups during those phases. Cancer relapse is characterized by a delay in growth before second line therapy for its relatively lower rate of mitosis compared by the primary cancer inducing a corresponding delay in the early detection. The therapeutic resistance of the cancer relapse is equivalent to the energy of the doses which have been delivered in the prior therapies, and requires increasing the administered dose by an amount equivalent to that resistance.
Dec 2025 DOI 10.14302/issn.2574-612X.ijpr-25-5849
Yılmaz GülsümCorresponding author
Bipolar disorder is a chronic condition marked by episodes of mania and depression, significant functional impairment, and challenges with treatment adherence. Current guidelines highlight the importance of both medication and psychosocial approaches in treatment. This review explores the primary psychosocial interventions for bipolar disorder. Psychoeducation helps recognize early symptoms, improves medication compliance, and prevents relapses. It is simple to implement and cost-effective. Family-Focused Therapy (FFT) enhances family communication, reduces emotional expression, and lowers the frequency of depressive episodes. Interpersonal and Social Rhythm Therapy (IPSRT) supports maintaining social stability by addressing disturbances in biological rhythms. Cognitive Behavioral Therapy (CBT) decreases depressive symptoms and boosts treatment adherence by restructuring automatic thoughts. Additionally, cognitive and functional rehabilitation programs improve attention, memory, and executive functioning. Peer support groups and digital e-health tools, though supportive, have limited evidence of effectiveness. In summary, multicomponent psychosocial interventions serve as a valuable addition to medication, helping to prevent relapses, improve functioning, and enhance quality of life in individuals with bipolar disorder.
Jul 2023 DOI 10.14302/issn.2470-5020.jnrt-23-4576
HECHAM N.Corresponding author
Background The evolution of multiple sclerosis (MS) is highly variable. Predicting this evolution at the beginning of the disease will help in the therapeutic management. The objective of this study was to describe the clinical characteristics and to identify early predictors of long-term disability among MS patients in Algeria. Methods We performed a descriptive and retrospective study of 400 MS patients followed over a 4-years period from July 2012 to July 2016 in the neurology department of Mustapha Bacha hospital in Algiers. The following parameters were systematically assessed for each patient: Age at onset, gender, relapses, initial demyelinating event, interval between first and second attack, residual deficit after first attack, onset of the progressive course, time of assignment of the successive scores of irreversible disability and type of disease modifying therapies. Univariate and multivariate Cox models were used to determine factors influencing time to Expanded Disability Status Scale (EDSS) 4 and 6. Results During the follow-up of this cohort of MS patients, a total of 144 (36%) and 83 (20%) patients reached EDSS scores 4 and 6 respectively. The median times from the onset of MS to assignment of a score 4 and 6 was 10 years and 19 years, respectively. Using the MSSS severity score, and after univariate analysis we identified several risk factors predictive of disease severity. These included male sex (P= 0.002), age of onset ≥ 40 years (P= 0.001), pyramidal (P= 0.0001), cerebellar (P= 0.002), and poly-symptomatic (P=0.0001) onset of the disease, incomplete recovery after the first attack (P= 0.0001), a high number of attacks during the first 2 years (P= 0.04) and the progressive form (P=0.001), and all these factors were correlated with a high MSSS score. However, prognostic factors in the multivariate binomial logistic regression analysis were limited to pyramidal onset, incomplete recovery after the first attack, short interval between the first and second attack, and progressive onset. Conclusion On the whole, the early predictive factors of disability in MS among Algerian patients were age of onset over 40 years, pyramidal onset, incomplete recovery after the first attack, short interval between the first and second attack and progressive form at onset. To increase the generalizability of findings, a national MS registry is strongly recommended, as well as long-term follow-up epidemiological studies.
Mar 2022 DOI 10.14302/issn.2692-1537.ijcv-22-4117
Wu JianqingCorresponding author
Healthier World (Independent researcher for cause), P. O. Box 689, Beltsville, MD 20704. USA
Several mRNA vaccines are used on the population in the U.S. I started predicting the dangers of mRNA vaccines before March 2021 and update my findings periodically. My prior model study enabled me to identify many flaws in clinical trials, side-effect evaluation methods and mechanism studies, and I also considered consistent failure in predicting drug side effects in the past and systematic failure of FDA in keeping out dangerous drugs from market. I found that the risks of vaccination cannot be determined by experiments alone and must be determined by using a combination of methods. By studying mRNA expression dynamics and kinetics, I predict that vaccination with mRNA vaccines may increase cancer risks, multiple organ failure risks, earlier death risks, genome alteration speeds by one or more mechanisms, alter the normal selection process for viral evolution resulting in more virulent viruses, and aggravate chronic diseases or cause healed diseases to relapse. Two root problems are practical inability to control expression sites and severe adverse reactions from repeated vaccination. Based on mRNA bio-distribution, the mRNA mainly strikes the liver and other vital organs, and poses grave dangers to persons whose vascular functional reserves are relatively small, or whose vascular systems are temporarily burdened by other causes such as viral infections or life activities. If an mRNA vaccine is administered on a pregnant woman by second or booster shots, spike protein synthesis in fetus brain disrupts the highly regulated protein synthesis processes, resulting in potential brain damages. In less than a year, most of my early predicted damages are being materialized or are on the track to hit the population. In this update, I present a benefits-and-risks map to show how the number of deaths caused by mRNA vaccines is grossly underestimated and why claimed benefits like 95% effectiveness rate and 90% death rate reduction are meaningless and misleading.
Jan 2022
PrachiCorresponding author
Senior Resident, Department of Pathology, Dharamshila Narayana Super speciality Hospital, New Delhi
This case report describes plasma cell pleocytosis occurring after bone marrow transplantation for multiple myeloma. The authors outline clinical presentation, cerebrospinal fluid findings, and differential diagnosis, emphasizing the need to consider hematologic relapse or CNS involvement in post‑transplant patients with neurologic symptoms. Management considerations and follow‑up strategies are discussed.
Nov 2019 DOI 10.14302/issn.2689-5773.jcdp-19-3061
Bajaj AnubhaCorresponding author
MD. (Pathology) Panjab University, Department of Histopathology, A.B. Diagnostics, A-1, Ring Road , Rajouri Garden, New Delhi, 110027, India.
Novel cancer therapeutics are superior and prevalent in the current scenario although a subset may not be satisfactorily alleviated or undergo disease relapse with the adoption of conventional chemotherapeutic agents. Cancer cells can comfortably elude immune destruction as interaction of cancer cells with native immune cells within tissue microenvironment is a cogent factor in evasion of cancer cells from pertinent immune surveillance. Thus, cancer immunotherapy can be safely contemplated as an efficacious and contemporary treatment modality for managing various malignant disorders.
May 2019 DOI 10.14302/issn.2574-4526.jddd-19-2770
Remy Andre-JeanCorresponding author
Mobile Hepatitis Team, Perpignan Hospital, France
Introduction In France 33% of patients didn’t take care of hepatitis C because there were no diagnosed. Drug injection was main contamination route of hepatitis C virus (HCV) in France. French guidelines were to treat all inmates and drug users, even fibrosis level. Access of HCV screening, care and treatment in drugs users, prisoners and homeless was low in France. They were considered as difficult to treat populations. All these patients need specific support. Hepatitis Mobile Team (HMT) was created in July 2013 to increase screening care and treatment of hepatitis B and C patients. HMT was composed of hepatologist, nurses, social workers and health care worker. Objective increase outreach screening care treatment access and cure of our target population. Patients and methods Target population was drugs users, prisoners, homeless, precarious people, migrants and psychiatric patients. We proposed part or all of our services to our 42 medical and social partners: HCV HBV screening by DBS (dried blood test); outside DBS and FIBROSCAN in converted van; Outreach open center; Drug users information and prevention, Free blood tests in primary care;, Staff training; Social screening and diagnosis; Mobile liver stiffness Fibroscan in site; Advanced on-site specialist consultation; Easy access to pre-treatment commission; Low cost mobile phones for patients; Individual psycho-educative intervention sessions; Collective educative workshops; Peer to peer educational program; Specific one day hospitalizations. All services were free for patients and for partners. Results from 2013 July to 2018 December, we did 8382 DBS for 5382 people (3053 HCV DBS) and 2302 Fibroscan*. HCV new positive rate was 21.3%. Our HCV active file was 651patients included these 24.8% new patients screened by DBS; 98% realized HCV genotype, HCV viral load and FIBROSCAN. DAA treatment was proposed to 96%; 95% started treatment, 4% were lost follow up or refused treatment. After treatment, there was 7 relapse and 3 reinfections by drug injection and cured rate of 94%. Sociological evaluation showed that 4 program qualities for patients: free access, closeness (outside hospital), speed (of the results) and availability (of nurse and social workers). Conclusions: Specific follow-up of drugs users and other HCV high-risk patients including screening, early detection, diagnosis and treatment increase rate of treated and cured patients, with low rate of relapse and reinfections.
May 2019 DOI 10.14302/issn.2328-0182.japst-19-2738
BARON AuroreCorresponding author
USMP Fleury Merogis, CH Sud Francilien
Rationale Prisons are major reservoirs of hepatitis C virus (HCV) in which a therapeutic approach has been particularly difficult so far. Prevalence of viral hepatitis C (HCV) is higher in prison environment in France than in the general population and is estimated to be 4,8%. The impact in prison environment is little-known as based on local studies. Inmate health care falls under USMP (prison setting medical unit), hospital specific units as by the january 18, 1994 law. Access to antiviral c treatment for inmates has always been difficult in France, would it be for interferon and ribavirin or use of protease inhibitors, with less than 20% of treated patients. French recommendations for HCV screening recommend systematic screening of inmates. The arrival of all oral therapies by direct antiviral agents (DAA) with shorter treatment times was an opportunity for doctors to propose a treatment and the patient to accept it. In 2014, the French guidelines recommended that HCV carriers in prison should systematically be treated independently of the stage of fibrosis. Objective of the Study PH8 Our objective was to evaluate the completion rate of an 8-week antiviral C treatment by sofosbuvir / ledipasvir regimen in non-cirrhotic genotype 1 patients in deprivation of liberty and achieve sustained virological response (SVR) and to measure the effectiveness of an 8-week treatment (by protocol analysis). Methodology prospective non-interventional multicenter trial among inmates with chronic hepatitis C genotype 1 with METAVIR fibrosis score F0 to F2 and who will receive a daily combination of sofosbuvir / ledipasvir for 8 weeks. Results 6 prison medical units included 115 consenting patients: there were 81% men, mean age 41 years (21 to 64 years). Route contamination was drug injection for 85%. HCV genotype was 1a for 74%, 1b for 24% and 2% none differenciated 1. Fibroscan mesure was available in 89 patients (mean score 3,5 KPa). Fibrotest was available in 37 patients with mean value 0.21. Eleven patients had Fibroscan and Fibrotest; 69% of patients were F0, 22% F1 and 9% F2. Average time between diagnosis and start of treatment was 3 weeks. We are sure that 109 patients (95%) completed DAA 8 weeks treatment; only 2 stopped DAA treatment before 8 weeks and 4 had no follow up after end of detention. HCV viral load was measured at W2 for 90 patients (78%), at W4 for 92 patients (78%), at end of treatment for 92 patients (78%), one month after treatment for 90 patients (78%) and 3 months after for 95 patients (93%). Only one viral load was positive, one month after treatment. Patient was retreated by sofosbuvir / velpastasvir. All HCV viral load 3 months after treatment negative; one patient took DAA only 6 weeks was cured. Conclusions In these study PH8, we observed completion rate of 94% for included patients in patient with 8 weeks ledipasvir/sofosbuvir regimen; data missed for only 4 patients and one relapsed. Short DAA treatment was efficient in prisoners and could be preferred in specific population.
Jan 2018 DOI 10.14302/issn.2470-5020.jnrt-17-1926
Nagel SimonCorresponding author
Department of Neurology, University of Heidelberg, Germany
Since the first description in 2013, 39 cases of anti-DPPX-encephalitis have been described. Main features of this autoimmune encephalitis characterized by antibodies against the potassium-channel-associated regulatory protein DPPX are gastrointestinal symptoms, cognitive dysfunction and signs of CNS hyperexcitability. While the majority of patients responds to immunotherapy relapses are frequent and often successfully treated with rituximab. Here we report another case of anti-DPPX-encephalitis presenting with the above mentioned triad. However, this is the first case of anti-DPPX-encephalitis in the context of a connective tissue disease combined with cerebral arteriopathy along with brain parenchymal lesions that we interpreted as a secondary, CTD-associated cerebral vasculitis. While the latter resolved under immunosuppressive treatment, comprising glucocorticosteroids, cyclophosphamide, rituximab and plasmapheresis, deterioration of the CTD and multiple infectious complications finally led to the patient's death. As histological evidence for cerebral vasculitis is lacking, other differential diagnoses for the observed cerebral arteriopathy, especially reversible cerebral vasoconstriction syndrome, have to be considered.
Feb 2016 DOI 10.14302/issn.2372-6601.jhor-15-822
I.V. ChernikovCorresponding author
Institute of Chemical Biology and Fundamental Medicine SB RAS.
Small interfering RNA (siRNA) based drugs for overcoming multiple drug resistance of hematological malignancies could solve the problem of poor response to the chemotherapy and hight relapse rate. The main factor that significantly limits biomedical application of siRNA is inefficient delivery to target cells and tissues. The attachment of siRNA to molecules, which enter into the cell by natural transport mechanisms, can improve cellular uptake of siRNA. In current study the carrier-free cellular uptake of siRNA containig cholesterol residues conjugated to the 5’-end of the sense strand via oligomethylene linker of various length (here and after Ch-siRNA) was explored. The data demonstrate that cholesterol residue increase the accumulation of siRNA in all tested cell lines and the primary cells. The efficiency of Ch-siRNA accumulation in K562 cells depends greatly on the leangth of the linker connecting cholesterol and siRNA: Ch-siRNAs with linker of 10 - 12 methylene units accumulate the most efficiently in this cells. It was found that Ch-siRNA effectively accumulates in MOLT-3 (acute lymphoblastic leukemia, ALL), HL-60 (acute myelogenous leukemia, AML), K562 (chronic myelogenous leukemia CML) and primary peripheral blood mononuclear cells (PBMC) from patient with non-Hodgkin lymphoma (NHL) or healthy donor resulting in near 100% of transfected cell when used at 1 mM concentration.
Jun 2015 DOI 10.14302/issn.2576-182X.jbsc-14-576
Gupta TejpalCorresponding author
Department of Radiation Oncology, Tata Memorial Hospital (TMH) and Advanced Centre for Treatment Research & Education in Cancer (ACTREC), Tata Memorial Centre, Parel, Mumbai: 400 012, INDIA
Multi-modality therapy has led to significant improvement in outcomes for childhood medulloblastoma; however, long-term survivors have become more susceptible to late effects of therapy including induction of second malignant neoplasms and even remain at an increased risk of late relapses including extra-neuraxial metastases. A newly detected solitary lytic/sclerotic osseous lesion in a medulloblastoma survivor away from the radiation field poses considerable diagnostic challenge as it could represent either a second malignant neoplasm or extra-neuraxial metastasis. We report one such case highlighting the importance of contemporary pathology techniques as useful adjuncts to differentiate a second primary osseous Ewing’s sarcoma (ES)/primitive neuro-ectodermal tumor (PNET) from bony metastasis and review the pertinent literature on second malignant neoplasms and extra-neuraxial metastases in medulloblastoma. To the best of our knowledge, this is the first report of a molecularly confirmed second primary osseous ES/PNET in a survivor of childhood medulloblastoma.
Jan 2015 DOI 10.14302/issn.2372-6601.jhor-14-377
Zaidah A WCorresponding author
Department of Haematology, School of Medical Sciences, Universiti Sains Malaysia,Kubang Kerian, Malaysia.
Background Abnormalities of plasma von Willebrand Factor (vWF) system has been described in solid tumors but more information is required to understand the pathophysiological process in haematological malignancies. Objectives This study was carried out to investigate the changes in vWF-related parameters including ADAMTS13 protein level in aggressive haematological malignancies and to identify the prevalence of anti-ADAMTS13 antibody as well as its correlations with vWF-related parameters. Patients/Methods Patient newly diagnosed or having relapse acute leukaemias or aggresive non-Hodgkin lymphomas were recruited into this study. Exclusion criterias include; pregnancy, patient already commenced chemotherapy, sepsis or has background congenital bleeding disorders. Blood specimen was subjected to; blood counts, ADAMTS13 protein, ADAMTS13 antibody detection, vWF:Ag, vWF activity, factor VIII level (FVIII) and vWF: CBA (collagen binding assays) Results and Conclusion A total of 60 subjects with median age at 42.5 (IQR: 23.25-57.5) were included. There were 34(56.7%) lymphomas and 26(43%) acute leukaemias. FVIII, vWF:Ag, wVF activity and vWF:CBA level were elevated whereas ADAMTS13 protein was reduced in majority of patients. Those with lymphomas showed significantly higher levels of FVIII, vWF:Ag, vWF:activity and vWF:CBA compared to the leukaemias. 38(63.3%) of patients showed presence of ADAMTS 13 autoantibody. There was however no correlation between ADAMTS13 protein and vWF-related parameters or with ADAMTS13 autoantibodies. There was a high prevalence of ADAMTS 13 autoantibodies in this cohort despite the absence of thrombotic thrombocytopenic purpura (TTP). The more pronounced changes in vWF-related parameters among aggressive lymphomas compared to acute leukaemias are in tandem with the marginally higher rates of venous thromboembolism in the former.
Feb 2014 DOI 10.14302/issn.2372-6601.jhor-13-346
E. Clapham ChloeCorresponding author
Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool, Liverpool, UK
Targeting cell metabolism is a therapeutic approach which has been used for the treatment of cancers with high levels of proliferation. Inhibition of metabolic processes in cancer cells has shown synergy with current therapeutic options to reduce refractory disease and relapse. In contrast, chronic lymphocytic leukaemia (CLL) is a disease where expansion of the malignant clone results from a combination of enhanced cell survival coupled with low level proliferation. The purpose of this article is to highlight how further research is needed to determine whether targeting cell metabolism may be a viable therapeutic strategy in this disease. We discuss how lymphocyte doubling time (LDT) remains a robust prognostic indicator used in the current clinical management of CLL, and how recognition of CLL as a proliferative disease has led to a greater understanding of the importance of energy-generating processes in its pathobiology. We summarize what is currently known about normal B cell metabolism and consider whether there is evidence of the Warburg effect in CLL cells. Finally, we speculate on how CLL cells may exploit protective mechanisms such as autophagy during times of metabolic stress and how they might influence or be influenced by metabolic characteristics of the microenvironment.