The Role Of Btkis In Sars
The BTKis ibrutinib and acalabrutinib have been hypothesized to have protective effects against COVID-19 by affecting macrophages and attenuating the immune response leading to weakened hyperinflammatory response and are currently being investigated in the treatment of COVID-19 . Treon et al. reported the impact of ibrutinib in 6 patients with Waldenstrom’s macroglobulinemia also infected with COVID-19. The investigators hypothesized that ibrutinib may protect against pulmonary lung injury based on positive results observed in a lethal flu animal model. Five of the 6 patients with Waldenstrom’s macroglobulinemia receiving ibrutinib 420 mg/day did not experience dyspnea, required no hospitalization, and showed steady improvement with resolution or near resolution of COVID-19-related symptoms. The sixth patient receiving 140 mg/day experienced progressive dyspnea and hypoxia requiring hospitalization and ultimately recovered after further treatment.
Thibaud et al. reported the outcomes of 8 patients receiving a BTKi for CLL and hospitalized with COVID-19. BTKi was held in 6 patients and continued in the remaining two. Two patients in the group that held BTKi developed respiratory failure, and the other patients had mild-to-moderate disease. The 2 patients continuing BTKi treatment had short hospital stays, minimal oxygen requirements, and recovered fully. No significant adverse events attributed to BTKi developed in either patient who continued BTKi therapy.
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Conflict Of Interest Statement
P.L. receives research grants from Janssen-Cilag and consulting honoraria from Janssen-Cilag, Abbvie, and Roche. B.E. has received personal fee from Janssen-Cilag, Roche, Novartis, Abbvie, Gilead, Celgene, ArQule, Astrazeneca, Oxford Biomedica, and Adaptive Biotechnologies and research funding from Janssen-Cilag, Roche, Abbvie, Gilead, and Beigene.
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Proteomic And Bioinformatic Profiling Of Neutrophils In Cll Reveals Functional Defects That Predispose To Bacterial Infections
Nirojah Subramaniam, Jenny Bottek, Stephanie Thiebes, Kristina Zec, Matthias Kudla, Camille Soun, Elena de Dios Panal, Julia K. Lill, Aaron Pfennig, Ralf Herrmann, Kirsten Bruderek, Sven Rahmann, Sven Brandau, Patricia Johansson, Hans Christian Reinhardt, Jan Dürig, Martina Seiffert, Thilo Bracht, Barbara Sitek, Daniel Robert Engel Proteomic and bioinformatic profiling of neutrophils in CLL reveals functional defects that predispose to bacterial infections. Blood Adv 2021 5 : 12591272. doi:
Sample Preparation And Liquid Chromatography With Tandem Mass Spectrometry Analysis
Cell-sorted neutrophils were lysed in 50 mM ammonium bicarbonate buffer containing 0.1% RapiGest Surfactant. The samples were reduced with 20 mM dithiothreitol for 30 min at 60°C and subsequently alkylated with 15 mM iodoacetamide for 30 minutes at room temperature protected from light. Proteins were digested using 22.5 ng trypsin per sample overnight. The digestion was stopped by adding 0.5% trifluoroacetic acid, and precipitated RapiGest was removed by centrifugation. Peptides were dried in vacuo and analyzed as described before. Briefly, 350 ng peptides in a volume of 15 µL 0.1% trifluoroacetic acid was subjected to an Orbitrap Elite mass spectrometer coupled to an Ultimate 3000 RSLCnano system. The peptides were preconcentrated for 7 minutes on a trap column and subsequently separated on an analytical column by a gradient from 5% to 40% solvent B over 98 minutes . Full-scan MS spectra were acquired in the Orbitrap analyzer, and the 20 most abundant peptides were selected for MS/MS analysis . Tandem spectra were measured in the linear ion trap following peptide fragmentation by collision-induced dissociation.
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Infectious Diseases Of The Urinary System Of Cats
, VMD, PhD, DACVIM, Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia
Most infections of the urinary system are caused by bacteria. The infection usually develops when bacteria enter the body through of the urethra. The bacteria then travel to the bladder, and in some cases they set up an infection there. Sometimes bacteria continue to move up the urinary tract to the kidneys and can result in kidney infection . There are several factors that increase the risk of urinary system infection. These include problems with urine flow , overly dilute urine, sugar in the urine , older age, a weakened immune system, and the presence of other diseases . Healthy adult cats are relatively resistant to urinary tract infections.
Treatment of bacterial urinary tract infections is important for several reasons. The bacteria that cause infections of the urinary tract can become resistant to antibiotics if the infections are not treated properly. Antibiotic resistance can lead to an infection that will not go away. In some cases, an untreated or inadequately treated bladder infection can be the cause of an infection in the kidneys, which is a more serious condition.
Altered Composition Of Neutrophil Granule Proteins And Dysfunctional Acidification Of Granules In Neutrophils In Cll
Next, we extended the characterization of neutrophils in regard to their functionality by performing GSEA of the most downregulated proteins of the pathways secretory vesicle and secretory granules . The analysis revealed proteins that are essential for neutrophil phagocytosis and degradation of bacterial components through granular compartments, such as lysozyme, elastase, and myeloperoxidase . Notably, proteomic data also unveiled an increased abundance of ceruloplasmin, an endogenous MPO inhibitor, in blood neutrophils of CLL-bearing mice . In order to study whether the altered expression of the proteins from the GSEA affects the effector functions of neutrophils in CLL, the expression of MPO and acidification of granules after phagocytosis were tested in blood neutrophils ex vivo through the ingestion of pH-sensitive fluorochrome-tagged E coli. FC demonstrates that neutrophils expressed significantly less MPO , suggesting impeded peroxidase activity of neutrophils in CLL . In line with this finding, we also observed a significantly reduced acidification in neutrophils in CLL after phagocytosis of pH-sensitive fluorochrome-tagged E coli . Collectively, these data show severe abnormalities of neutrophil effector functions in CLL-bearing mice.
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Symptoms In Young Children
Symptoms of leukemia can be difficult to detect in younger children who may only able to communicate by crying. The only other signs may be as a lack of appetite, the refusal to eat, or the appearance of a limp due to a bone or joint pain.
Some of the symptoms are easier to understand in the context of the effect leukemia has on specific blood cells produced by the bone marrow, since many of the signs are related to either an excess or deficiency of these cells.
Leukemia affects white blood cells, but also frequently affects other cells produced by the bone marrow by interfering with their production or crowding out the bone marrow. Cells manufactured by the bone marrow include:
- Red blood cells : Red blood cells carry oxygen to the tissues of the body. A low red blood cell count is referred to as anemia.
- White blood cells : WBCs fight off infections due to organisms such as bacteria and viruses. A low WBC count is referred to as leukopenia. One type of WBC, neutrophils, are particularly important in fighting off the bacteria that cause infections such as pneumonia. A deficiency of neutrophils is referred to as neutropenia.
- Platelets: Platelets or thrombocytes are the cells produced by the bone marrow that are responsible for blood clotting. A low platelet count is referred to as thrombocytopenia.
Resources For More Information
American Cancer Society. Chronic Lymphocytic Leukemia. CLL.
Conte, M. J., Parikh, S. A., Bowen, D. A., Call, T. G., Kabat, B. F., Chaffee, K. G., … & Shanafelt, T. D. . The Role of Splenectomy in the Care and Treatment of the CLL Patient.
Eichhorst, B et al. Chronic lymphocytic leukemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 21:v162-v164.
Eichhorst B et al. Initial therapy of chronic lymphocytic leukemia. Seminars in Oncology. 2016. 43:241-250.
Gaidano, G., & Rossi, D. . The mutational landscape of chronic lymphocytic leukemia and its impact on prognosis and treatment. ASH Education Program Book, 2017, 329-337.
Hallek, M., Cheson, B. D., Catovsky, D., Caligaris-Cappio, F., Dighiero, G., Döhner, H., … & Stilgenbauer, S. . Guidelines for diagnosis, indications for treatment, response assessment and supportive management of chronic lymphocytic leukemia. Blood, blood-2017.
Lucas, F. M., & Gribben, J. . Chronic lymphocytic leukemia. Clinical Manual of Blood and Bone Marrow Transplantation, 123-130.
Magalhaes, I., Kalland, I., Kochenderfer, J. N., Österborg, A., Uhlin, M., & Mattsson, J. . CD19 Chimeric Antigen Receptor T Cells From Patients With Chronic Lymphocytic Leukemia Display an Elevated IFN- Production Profile. Journal of Immunotherapy, 41, 73-83.
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Common Infections In Pregnant Mums Linked To Leukemia Risk In Children
Common maternal infections during pregnancy, such as urinary and respiratory tract infections were linked to a child developing leukemia, a new study has found. But the increase in overall risk was small given the rarity of childhood leukemia.
Researchers looked at whether childhood leukaemias including acute lymphoblastic leukemia and acute myeloid leukemia or any other childhood cancer occurred more frequently in children whose mothers had self-reported common infections during their pregnancy.
The study, led by the Murdoch Children’s Research Institute and the University of Oxford and published in the International Journal of Epidemiology, found that while urinary tract and respiratory tract infections were associated with childhood leukemia, the increase in overall risk was small given the rarity of a child developing this form of cancer.
The International Childhood Cancer Cohort Consortium study analyzed data from Australia, Denmark, Israel, Norway, the UK and the US. More than 300,000 children were recruited for the study over 60 years between the 1950s until the 2000s.
Senior author of the study and Director of I4C International Data Coordinating Centre, based MCRI, Professor Terry Dwyer, said that the results were reassuring for parents.
Professor Dwyer said innovative projects like the I4C study could provide the greatest opportunity to find a preventable cause of childhood cancer.
Renal Infiltration And Obstruction
The renal parenchyma is infiltrated by monomorphic lymphocytes with an immunotype characteristic of CLL/small lymphocytic lymphoma. Immunohistochemistry stains reveal strongly positive B-cell marker CD20, negative T-cell marker CD3 and aberrantly expressed T-cell marker CD5.
Obstructive nephropathy in the setting of CLL can be observed and is diagnosed radiographically via ultrasound, MRI or CT scan. Bilateral hydronephrosis from obstructing nodes is managed with decompression and treating the underlying CLL .
What Is A Urinary Tract Infection
A urinary tract infection is a bacterial infection in any part of your urinary tract. Your urinary tract is the interconnected system of organs that make and store urine. The sections of the urinary tract include:
- Kidneys: The organs that filter waste from your blood and convert the waste and water into urine.
- Bladder: A sac-like organ that stores urine before it leaves your body.
- Ureters: Thin tubes that carry urine from your kidneys to your bladder.
- Urethra: A tube that allows urine to leave your body. â
You can get an infection in any part of the urinary tract. The most common type of UTI is called cystitis, and it is an infection in the bladder. You can also have an infection in the urethra known as urethritis. An infection in the kidneys is known as pyelonephritis and it is the most severe type of UTI.
Treating Urinary Tract Infections
Since bacteria cause UTIs, youll need an antibiotic to treat them. Usually, a short course lasting a few days is all you need to treat a simple UTI. Your symptoms should improve after a couple of days, but its important to take the whole course of . Skipping doses or not taking the full course could cause the UTI to come back and it may be harder to treat. Your doctor may also give you medicine to numb your urinary tract until the antibiotic starts working. Your urine may turn orange while you take this medicine.
Drink plenty of fluids while you are on treatment for a UTI. Water is the best choice. Avoid drinks with caffeine or alcohol. They can irritate the bladder and cause .
If you get frequent UTIsthree or more in a yeartalk with your doctor. You may need preventive antibiotics. This may mean a daily antibiotic or just taking one when you know youre at risk, such as after sex. Other prevention strategies include drinking plenty of fluids, not holding your urine for long periods, urinating after sex, and using lubrication during sex.
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String And Gsea Identify Aberrations In Neutrophil Functionality In Cll And Provide Targets For Therapeutic Interventions
Identification of proteins involved in increased IFN signaling in blood neutrophils during CLL. GSEA of the proteome of blood neutrophils indicated a significant enrichment of IFN and IFN response. The positive enrichment score indicates the contribution of those proteins that are overexpressed in blood neutrophils in CLL-bearing mice. Detailed expression values are shown in supplemental Tables 7 and 8. Analysis of the enrichment score indicated 31 significantly enriched proteins of the pathway IFN response and 18 proteins of the pathway IFN response . The heatmap indicates the expression intensities of proteins of both pathways, IFN and – response,” in blood neutrophils of CLL-bearing mice. A machine learning algorithm of the proteome of blood neutrophils in CLL indicates best features in according to logarithmic abundancies. A RFC was used to calculate the Gini decrease. RLM, ranked list metric. Non-CLL, n = 6 CLL, n = 12.
What To Do About Changes When You Urinate
Narrator:What to do about changes when you urinate caused by radiation therapy.
Having problems when you urinate? Listen to solutions from other people undergoing radiation therapy. Also, hear advice from Dr. Ross. Then talk with your own doctor or nurse to learn more.
Miguel:Tip number 1: Drink lots of liquids each day.It’s good for your urine to be clear or a pale yellow color. My doctor says that tells you you’re getting enough liquids. Most people find drinking about 8 cups of liquid a day does the trick. Of course, check to make sure that’s the best amount for you, too.
Cara:Tip number 2: Water is wonderful, but you may want more zip in your sip.I like water, but found it was hard to get enough water each day. I was glad to learn that Jell-O and soups also count as liquids. To add some zip to what I drink, I have water with a little lemon and watered-down juices.
Rodney:Tip number 3: Lose the booze.My doctor told me that wine, liquor, or even beer could really bother my bladder. So now I limit these liquids. Some people may need to stay away from wine, liquor, and beer altogether to avoid irritating their bladder.
My doctor also told me to stay away from caffeine in coffee, colas, or teas. They could make my bladder problems worse. I now choose flavored decaf coffees and tasty herbal teas.
Dr. Ross:Hi, I’m Dr. Ross and you just heard 3 great tips to keep bladder problems under control.
- January 23, 2020
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Sll Stage System/lugano Modification Of The Ann Arbor Staging System
One node or a group of adjacent nodes
Single extranodal lesions without nodal involvement
Two or more nodal groups on the same side of the diaphragm
Stage I or II by nodal extent with limited contiguous extranodal involvement
Stage II bulky
II as above with bulky disease
Nodes on both sides of the diaphragm
Modes above the diaphragm with spleen involvement
Additional non-contiguous extra lymphatic involvement
There are a few other features that help clinicians determine how quickly treatment is needed:
- The presence of CD38 on the surface of CLL cells.
- Lymphocyte doubling time, which is the time it takes for the count to double. Taking longer than 12 months to double is considered lower risk, faster than this is considered higher risk disease.
- The extent to which the bone marrow is involved can be prognostic and can help to determine treatment.
Aberrant Expression Of Surface Molecules Important For Neutrophil Migration
A distinct phenotype of blood neutrophils in CLL indicates aberrant migration during UTI. Mice were induced with CLL, and the expression of CD62L and CXCR4 was determined on neutrophils by FC . Dot plots indicate phenotypic alterations in protein surface expression on blood neutrophils of non-CLL and CLL-bearing mice . Control stainings are indicated as fluorescence minus one . Mice were euthanized on day 42 post-CLL induction with a tumor burden > 20%. The frequency of neutrophils for CD62L and CXCR4 was determined by FC. Linear regression analysis of the indicated surface molecules on murine blood neutrophils. The CLL burden and frequencies of neutrophil subsets positive for CD62L and CXCR4 were determined by FC. The expression of the surface molecules CD62L and CXCR4 was determined on blood neutrophils from patients with CLL . Dot plots illustrate the phenotypic alterations in protein expression in patients with low CLL load vs high CLL load analyzed by FC. Isotype control staining is also shown . Linear regression analysis of CD62L and CXCR4 on blood neutrophils from patients with CLL . Incidence rate of respiratory infections in correlation to CLL burden . *P< .05. Data represent mean ± SEM. Non-CLL, n = 5 CLL, n = 3. Patients with CLL, n = 14. Pregated on Ly6G+ neutrophils . Pregated on CD45dim/high and CD16/+, CD45high CD16 eosinophils were excluded .
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