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Simple Summary: Bruton's tyrosine kinase inhibitors (BTKi) have revolutionized the treatment of various B-cell lymphoid malignancies. However, acquisition of resistance to BTKi has emerged as an important clinical challenge. Herein, we provide a detailed review, describing the clinical trials that led to the FDA approval of the BTK inhibitors for management of Chronic Lymphocytic Leukemia (CLL), Mantle Cell Lymphoma, Marginal Zone Lymphoma (MZL), Follicular Lymphoma (FL) and Waldenstrom Macroglobulinemia (WM). We describe the mechanism of intrinsic and extrinsic resistance to the BTKi with main emphasis on the functional description of BTK mutations in CLL. Finally, we review the latest updates of the PROTACs BTK degraders, an evolving treatment modality for the management of the BTKi refractory B-cell malignancies. B-cell lymphoid malignancies are a heterogeneous group of hematologic cancers, where Bruton's tyrosine kinase (BTK) inhibitors have received FDA approval for several subtypes. The first-in-class covalent BTK inhibitor, Ibrutinib, binds to the C481 amino acid residue to block the BTK enzyme and prevent the downstream signaling. Resistance to covalent BTK inhibitors (BTKi) can occur through mutations at the BTK binding site (C481S) but also other BTK sites and the phospholipase C gamma 2 (PLCγ2) resulting in downstream signaling. To bypass the C481S mutation, non-covalent BTKi, such as Pirtobrutinib, were developed and are active against both wild-type and the C481S mutation. In this review, we discuss the molecular and genetic mechanisms which contribute to acquisition of resistance to covalent and non-covalent BTKi. In addition, we discuss the new emerging class of BTK degraders, which utilize the evolution of proteolysis-targeting chimeras (PROTACs) to degrade the BTK protein and constitute an important avenue of overcoming resistance. The moving landscape of resistance to BTKi and the development of new therapeutic strategies highlight the ongoing advances being made towards the pursuit of a cure for B-cell lymphoid malignancies. [ABSTRACT FROM AUTHOR]

To examine the effects of an Arabic smartphone application on adherence to home exercise programs (HEPs) and the effectiveness of mobile-based HEPs on pain, physical function, and lower-limb muscle strength among older women with knee osteoarthritis (OA). This randomised control trial (ClinicalTrials.gov: (NCT04159883) enrolled 40 women aged ≥50 years with knee OA who were randomised into the app group (experimental; n = 20) receiving HEPs using an Arabic smartphone application called "My Dear Knee", whereas the paper group (control; n = 20) receiving HEPs as hand-outs. Both groups had the same exercise program. Outcome measures were self-reported adherence, changes in the Arabic Numeric Pain Rating Scale, the Arabic version of the reduced Western Ontario, McMaster Universities Osteoarthritis Index-Physical Function subscale, and Five-Times Sit-To-Stand Test scores. All participants were assessed at baseline, at week 3 and week 6. Using completer-only analyses, the repeated measures ANOVA was used to compare the means of the outcome measures between the two groups. At the end of week 6, the app group reported greater adherence to HEPs (p =.002) and significant reduction in pain (p =.015). A smartphone application with motivational and attractive features could enhance adherence to HEPs in this patient cohort. Older adults with knee OA may face many obstacles that prevent or limit their adherence to the prescribed HEP. Smart device apps supported with attractive and motivational features could be an effective strategy to enhance adherence to HEPs among older adults with knee OA. Using such remote technology appears to overcome the barriers that may limit the ability of older women to receive supervised physical therapy in a clinical setting. [ABSTRACT FROM AUTHOR]