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Molecular mechanisms of the preventable causes of cancer in the United States.

Annually, there are 1.6 million new cases of cancer and nearly 600,000 cancer deaths in the United States alone. The public health burden associated with these numbers has motivated enormous research efforts into understanding the root causes of cancer. These efforts have led to the recognition that between 40% and 45% of cancers are associated with preventable risk factors and, importantly, have identified specific molecular mechanisms by which these exposures modify human physiology to induce or promote cancer. The increasingly refined knowledge of these mechanisms, which we summarize here,

Incidence and cost of treatment-emergent comorbid events in insured patients with chronic hepatitis C virus infection: a retrospective cohort study.

BackgroundTreatment-emergent comorbid events (TECs) are common In patients initiating treatment with pegylated interferon alpha (PEG-IFN-alfa) and ribavirin for chronic hepatitis C virus (HCV) infection. The purpose of this study was to estimate the incidence and incremental cost of these events.MethodsIn a retrospective cohort analysis of healthcare claims, we studied patients with HCV who were newly treated with PEG-IFN-alfa/ribavirin between 2006 and 2008. TECs were defined by new medical/pharmacy claims for predefined conditions in the 12 months after treatment initiation. The net incremen

Импайримент митохондрий скелетных мышц у пациентов с новой диагностированной множественной склерозом, выявленный ¹H/³¹P магнитно-резонансной спектроскопией.

Нарушение функции митохондрий участвует в патофизиологии множественной скlerоза (МС) и может способствовать его усталости и слабости мышц. Являются ли метаболические изменения скелетных мышц присутствующими на этапе начала заболевания — неясно. В этой наблюдательной изученной парой случаев и контрольной группы мы исследовали метаболизм мышц и его связь с системными метаболическими показателями у новых пациентов с МС (ПМС), не подвергшихся лечению, и соответствующих здоровых контрольных групп. Метаболизм гастроцинемия оценивался с помощью статической и динамической 7 Т 1H/31P магнитно-резонансн

Harnessing live vectors for cancer vaccines: Advancing therapeutic immunotherapy.

Cancer vaccines represent a promising approach within immunotherapies. These vaccines are tailored to target tumor-specific antigens, thereby offering a precision approach to cancer treatment. The key principles in developing therapeutic cancer vaccines include identifying appropriate vaccine targets and selecting effective vaccine delivery platforms. These delivery platforms are diverse and have evolved to enhance the immune response. This review explores live cancer vaccines and the biological entities involved. Live cancer vaccines leverage the use of various biological entities to stimulat

Anti-BCMA CAR T-cell therapy CT103A in relapsed or refractory AQP4-IgG seropositive neuromyelitis optica spectrum disorders: phase 1 trial interim results.

Chimeric antigen receptor (CAR) T-cell therapy that targets B-cell maturation antigen (BCMA) have great potentials in autoimmune diseases and could be novel therapeutics for relapsed/refractory neuromyelitis optica spectrum disorder (NMOSD). To evaluate the safety and efficacy of the CT103A, a self-developed BCMA-targeting CAR construct against BCMA, in patients with AQP4-IgG seropositive NMOSD, an ongoing, investigator-initiated, open-label, single-arm, phase 1 clinical trial is conducted at our center. In total, 12 patients were administered with a CAR-BCMA infusion. Ten of the 12 patients d

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… Hypocalcemia 1 (8) 0 (0) Hypokalemia 1 (8) 1 (8) Blood fibrinogen decreased 1 (8) 0 (0) NT-proBNP increased 2 (17) 0 (0) Myocardial strain 1 (8) 0 (0) Hypogammaglobulinemia 11 (92) 0 (0) Cytokine release syndrome 12 (100) 0 (0) Neurologic toxic effect 0 (0) 0 (0) CMV cytomegalovirus infection, BKV BK … to trial regimen CMV cytomegalovirus infection, BKV BK virus, EBV Epstein–Barr virus, APTT activated partial thromboplastin time, NT-proBNP N-terminal pro-brain natriuretic peptides, AST aspartate aminotransferase, ALT alanine aminotransferase, LDH lactate dehydrogenase Variable | All patients ( N = …

Surveillance of the current situation regarding influenza vaccination according to medical oncologists in Japan.

This study aimed to clarify the attitude of oncologists toward influenza vaccination and the current situation and issues regarding influenza vaccination for patients on chemotherapy in Japan. A web-based survey of medical oncologists certified by the Japanese Society of Medical Oncology was conducted between November 1 and December 31, 2019. Of the 1369 medical oncologists who were invited to participate, 415 (30.3%) responded to our survey. The questionnaire comprised 4 sections: "oncologist characteristics," "oncologist attitude toward influenza vaccines and the current status of influenza

Clinical Usefulness of Bronchoalveolar Lavage in the Management of Pulmonary Infiltrates in Adults with Hematological Malignancies and Stem Cell Transplantation.

IntroductionPulmonary complications are frequent in patients with hematologic malignancies and stem cell transplantation. Regardless of the microbiological usefulness of bronchoalveolar lavage (BAL), little information exists on both its benefits as a guide for therapeutic decisions and its impact on patients' clinical outcome.MethodsA prospective observational single-center study was performed between July 2011 and July 2016. Consecutive episodes of pulmonary infiltrates were analyzed in subjects over 18 years of age who presented hematologic malignancies and underwent chemotherapy or stem ce

Management of Immunosuppression in Kidney Transplant Recipients Who Develop Malignancy.

The risk of cancer increases after transplantation. However, the consensus on immunosuppression (IS) adjustment after diagnosis of malignancy is lacking. Our study aims to assess the impact of IS adjustment on mortality of post-kidney transplant patients and allograft outcomes. We retrospectively reviewed the data in our center of 110 subjects. Our results showed IS dose adjustment was not statistically associated with mortality risk (HR 1.94, 95%CI 0.85-4.41, p = 0.12), and chemotherapy was the only factor that was significantly related to mortality (HR 2.3, 95%CI 1.21-4.35, p = 0.01). IS red

Case report: Relapsed/refractory extranodal natural killer/T-cell lymphoma nasal type with extensive central nervous system involvement.

Background: Extranodal natural killer/T-cell lymphoma (ENKL) is a rare subtype of mature T and natural killer cell lymphomas associated with Epstein-Barr virus. Case: A 20-year-old presented with severe neurological symptoms and was diagnosed with stage IV ENKL, nasal type, with CNS involvement. Overall, the patient received nine treatment lines, including chemotherapy, craniospinal irradiation, allogeneic stem cell transplant (alloSCT), donor lymphocyte infusions, and novel agents (Nivolumab, Daratumumab, Thalidomide, Lenalidomide, virus-specific T cells) combined with intrathecal chemotherap

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… Allogeneic BK virus–specific T cells for progressive multifocal leukoencephalopathy. N Engl J Med 379(15):1443–51. 10.1056/NEJMoa1801540 26. Seo S, Kami M, Honda H, Kashima T, Matsumura T, Moriya A, et al. …

Hairy cell leukemia in kidney transplantation: lesson from a rare disorder.

We report here on the diagnosis and successful treatment of a case of hairy cell leukemia (HCL) that arose 15 years after kidney transplantation in a 51-year-old patient. As soon as the diagnosis was made, HCL was treated with 2-CDA, obtaining complete hematological remission. Immunosuppression with the calcineurin inhibitor cyclosporin was maintained, and the graft was preserved. In kidney transplant recipients supported with immunosuppressive drugs, post-transplant lymphoproliferative diseases (PTLDs) are frequent and typically related to immunosuppression via a loss of control of infectious

Post-Transplant Cyclophosphamide for the Prevention of Graft-vs.-Host Disease in Allogeneic Hematopoietic Cell Transplantation: A Guide to Management for the Advanced Practitioner.

Cyclophosphamide remains a critical component to haploidentical transplant conditioning regimens. Post-transplant cyclophosphamide (PTCy) emerged as an effective component of graft-vs.-host disease (GVHD) prophylaxis in the nonmyeloablative haploidentical bone marrow transplant setting. The relative ease of administration compared with ex vivo manipulations and efficacy in reducing GVHD has led to increasing PTCy use in transplant centers around the world. The role of PTCy has expanded to haploidentical transplantation with myeloablative conditioning regimens and peripheral blood progenitor ce

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… Hemorrhagic cystitis that occurs soon after the administration of cyclophosphamide is thought to be related to drug exposure, whereas late-onset HC is often attributed to a variety of factors including viral infections (BK virus, cytomegalovirus, adenovirus), intensity of conditioning regimen, thrombocytopenia … A few studies conducted in the PTCy setting discuss the incidence of HC; however, these cases are related to BK virus ( Shah et al., 2019 ; Solomon et al., 2014 ). The definition of early-onset HC is difficult to describe as it varies significantly from study to study. …

Adoptive T-cell therapy for Leukemia.

Allogeneic stem cell transplantation (alloSCT) is the most robust form of adoptive cellular therapy (ACT) and has been tremendously effective in the treatment of leukemia. It is one of the original forms of cancer immunotherapy and illustrates that lymphocytes can specifically recognize and eliminate aberrant, malignant cells. However, because of the high morbidity and mortality that is associated with alloSCT including graft-versus-host disease (GvHD), refining the anti-leukemia immunity of alloSCT to target distinct antigens that mediate the graft-versus-leukemia (GvL) effect could transform

MR and CT angiography in the diagnosis of vasculitides.

Vasculitides represent the wide-ranging series of complex inflammatory diseases that involve inflammation of blood vessel walls. These conditions are characterized according to the caliber of the predominantly involved vessels. The work-up of vasculitides often includes imaging to narrow a differential diagnosis and guide management. Findings from CT and MR angiography in conjunction with a thorough history and physical exam are of utmost importance in making an accurate diagnosis. Further, imaging can be used for follow-up, in order to monitor disease progression and response to treatment. Th

Exercise and the immune system: taking steps to improve responses to cancer immunotherapy.

The remarkable success of cancer immunotherapies has provided new hope to cancer patients. Unfortunately, a significant proportion of patients remain unable to respond to immunotherapy or maintain durable clinical responses. The lack of objective responses likely results from profound immune dysfunction often observed in patients with cancer. There is substantial evidence that exercise and physical activity can reduce incidence and improve outcomes in cancer patients. As the immune system is highly responsive to exercise, one potential avenue to improve immune function is through exercise and

Hypophosphatemic Osteomalacia Associated with Adefovir-induced Fanconi Syndrome Initially Diagnosed as Diabetic Kidney Disease and Vitamin D Deficiency.

A 68-year-old man with type 2 diabetes mellitus and chronic hepatitis B infection was referred to the nephrology department before planned surgery for hepatocellular carcinoma. He had been receiving low-dose adefovir dipivoxil (ADV) for 11 years. Laboratory findings revealed impaired re-absorption in the proximal renal tubules. He had been diagnosed with diabetic kidney disease and osteomalacia due to vitamin D deficiency; thus, ADV was not discontinued until he was referred to us. In this case, concomitant diabetes mellitus and vitamin D deficiency might have prevented the early diagnosis of

GvHD prophylaxis with tacrolimus, sirolimus, and mycophenolate mofetil after reduced intensity conditioning hematopoietic stem cell allogeneic transplantation.

We present the largest prospective real-world experience in 159 patients who received the triple combination of tacrolimus/sirolimus/mycophenolate mofetil after reduced intensity conditioning allogeneic hematopoietic stem cell transplantation (RIC-alloHSCT) from matched-related (MRD), matched-unrelated (MUD) or mismatched-unrelated donors (MMURD). Despite the high-risk and elderly population, non-relapse mortality (NRM) at day +100 and 1 year was 5.1% and 8.6%. Grades 2-4 and 3-4 acute Graft-versus-host disease (GvHD) at day +180 was 30.3% and 13%, respectively. Chronic GvHD at 1 and 3 years w

Case Report: Kidney Transplantation in a Patient With Acquired Agammaglobulinemia and SLE. Issues and Challenges.

Lupus nephritis in the context of Systemic Lupus Erythematosus (SLE) is characterized by an unpredicted course with remissions and flare-ups. Among others, it remains a significant cause of end-stage kidney disease (ESKD) in relatively young patients. Therapeutic regimens with newer immunosuppressive agents have been introduced in order to control SLE clinical manifestations more efficiently and limit organ damage induced by immune complex formation and sustained inflammation. Treatment is usually long-term, and the cumulative impact of immunosuppression is expressed through the increased freq

Potential Targeting Mechanisms for Bone-Directed Therapies.

Bone development is characterized by complex regulation mechanisms, including signal transduction and transcription factor-related pathways, glycobiological processes, cellular interactions, transportation mechanisms, and, importantly, chemical formation resulting from hydroxyapatite. Any abnormal regulation in the bone development processes causes skeletal system-related problems. To some extent, the avascularity of cartilage and bone makes drug delivery more challenging than that of soft tissues. Recent studies have implemented many novel bone-targeting approaches to overcome drawbacks. Howe

Clinical transplantation and tolerance: are we there yet?

Organ transplantation is not only considered as the last resort therapy but also as the treatment of choice for many patients with end-stage organ damage. Recipient-mediated acute or chronic immune response is the main challenge after transplant surgery. Nonspecific suppression of host immune system is currently the only method used to prevent organ rejection. Lifelong immunosuppression will cause significant side effects such as infections, malignancies, chronic kidney disease, hypertension and diabetes. This is more relevant in children who have a longer life expectancy so may receive longer

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… CMV infection, BK virus nephropathy and Pneumocystis carinii pneumonia (PCP) are among other complications [ 15 ]. In general, infection, as the main cause of hospitalization after kidney transplantation, is related to immunosuppression [ 8 , 16 ]. …

Liver disease during and after hematopoietic stem cell transplantation in adults: a single-center Egyptian experience.

BACKGROUND: Hepatic complications are a well-known cause of both early and late mortality and morbidity in hematopoietic stem cell transplant (HSCT) recipients. Early diagnosis and management of hepatic complications is important in order to commence appropriate therapy. Conditioning regimens, acute and chronic graft versus host disease, sinusoidal obstruction syndrome, and infections among others represent major hepatic complications for the transplant recipient. We assessed liver function tests, viral markers, polymerase chain reaction, abdominal ultrasound, portal, and hepatic venous duplex