A hallmark feature of tumorigenesis is uncontrolled cell division. Autophagy is regulated by more than 30 genes and it is one of several mechanisms by which cells maintain homeostasis. Autophagy promotes cancer progression and drug resistance. Several genes play important roles in autophagy‐induced tumorigenesis and drug resistance including Beclin‐1, MIF, HMGB1, p53, PTEN, p62, RAC3, SRC3, NF‐2, MEG3, LAPTM4B, mTOR, BRAF and c‐MYC. These genes alter cell growth, cellular microenvironment and cell division. Mechanisms involved in tumorigenesis and drug resistance include microdeletions, genetic mutations, loss of heterozygosity, hypermethylation, microsatellite instability and translational modifications at a molecular level. Disrupted or altered autophagy has been reported in hematological malignancies like lymphoma, leukemia and myeloma as well as multiple solid organ tumors like colorectal, hepatocellular, gall bladder, pancreatic, gastric and cholangiocarcinoma among many other malignancies. In addition, defects in autophagy also play a role in drug resistance in cancers like osteosarcoma, ovarian and lung carcinomas following treatment with drugs such as doxorubicin, paclitaxel, cisplatin, gemcitabine and etoposide. Therapeutic approaches that modulate autophagy are a novel future direction for cancer drug development that may help to prevent issues with disease progression and overcome drug resistance.

Standard induction therapy for multiple myeloma is three-drug combination based on following classes of drugs: proteasome inhibitors, immunomodulators and steroids. Despite its notable efficacy, bortezomib has side effects like peripheral neuropathy (PNP) with reported incidence of grade ≥3 PNP between 2%-23% Schlafer et al., 2017. Carfilzomib (CFZ) has high selectivity and minimal off-target adverse effects including lower rates of PNP. CFZ is already approved for treatment of relapsed and refractory multiple myeloma (RRMM) as single agent as well as in combination with lenalidomide and/or dexamethasone. Extensive literature search identified a total of 1839 articles. Twenty-six articles (n = 5980) met the inclusion criteria, 15 in newly diagnosed multiple myeloma (NDMM) and 11 in RRMM group. CFZ demonstrates comparable or even better efficacy to bortezomib with much favorable AE profile. Deep, rapid and sustainable response using KRd with safer toxicity profile supports extension of KRd therapy to frontline therapy for all risk categories of MM. High incidence of grade ≥3 HTN underscores the importance of serial BP monitoring. In RRMM, CFZ has documented efficacy with standard 20-27mg/m2 dose. Further large-scale trials are needed to study benefit-to-risk profile of 20-56 and 20-70 mg/m2 dose of CFZ vs standard 20-27 mg/m2 dose in NDMM and RRMM.

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Background: Atrial Fibrillation (AFib) is the most common cardiac arrhythmia, occurring in ≈1% of the general population. An increased risk of malignancy among patients with AFib would be of substantial public health importance, given the high prevalence and associated economic burden of both disorders. Objectives: To evaluate the relationship between atrial fibrillation (AFib) and cancer. Methods: We conducted an extensive database search on PubMed, Google Scholar, ScienceDirect, and SEER Database from their inception to September 2019 for any study that evaluated the association between AFib and cancer. Results: In the first 3 months of AFib diagnosis, Ostenfeld et al. reported an absolute cancer risk of 2.5% with a standardized incidence ratio of 7.02 and 3.53 for metastatic and localized cancer, respectively. Likewise, Saliba et al. detected an increase in the odds of cancer diagnosis in first 90 days after AF diagnosis with OR of 1.85. Moreover, in another study newonset breast and colorectal cancer was especially associated with AF in the first 90 days after diagnosis with HR of 3.4 but not thereafter (HR 1.0). Similarly, Conen et al. reported high relative risk of cancer with HR of 3.54 in the first 3 months after new-onset AFib. However, beyond the initial 90 day period, the risk of cancer in AFib is only slightly increased. Conclusion: Based on our review, there appears to be an increase in risk of subsequent diagnosis of cancer in patients with AF, likely owing to the shared risk factors between the two conditions. While the results of this study raise interesting questions for future search, they are not currently strong enough to justify initiating cancer screening for an occult cancer in a patient with AF. Regardless, measures to target modification of these shared risk factors remains an important consideration.

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Introduction: Since the approval of transcatheter aortic valve replacement (TAVR), nonagenarian group patients are being increasingly considered for TAVR. Therefore, we compared the clinical outcomes of surgical aortic valve replacement (SAVR) vs TAVR in nonagenarians with severe aortic stenosis. Methods: A literature search was performed using MEDLINE, Embase, Web of Science, Cochrane, and Clinicaltrials.gov for studies reporting the comparative outcomes of TAVR versus SAVR in nonagenarians. The primary endpoint was short-term mortality. Secondary endpoints were post-operative incidences of stroke or transient ischemic attack (TIA), vascular complications, acute kidney injury (AKI), transfusion requirement, and length of hospital stay. Results: Four retrospective studies qualified for inclusion with a total of 8,389 patients (TAVR = 3,112, SAVR = 5,277). Short-term mortality was similar between the two groups [RR = 0.91 (95% CI: 0.76-1.10), p = 0.318]. The average length of hospital stay was shorter by 3 days in the TAVR group (p = 0.037). TAVR was associated with a significantly lower risk of AKI [RR = 0.72 (95% CI: 0.62-0.83), p < 0.001] and a lower risk of transfusion [RR = 0.71 (95% CI: 0.62-0.81), p < 0.001]. There was no difference in risk of stroke/TIA[RR = 1.01 (95% CI: 0.70-1.45), p = 0.957]. The risk of vascular complications was significantly higher in the TAVR group [RR = 3.39 (95% CI: 2.65-4.333), p < 0.001]. Conclusion:In this high-risk population, TAVR compared to SAVR has similar short-term mortality benefit but has lower risks of perioperative complications and a higher number of patients being discharged to home.

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Vaccination is an effective strategy to prevent infections in immunocompromised hematopoietic stem cell transplant recipients. Pretransplant vaccination of influenza, pneumococcus, Haemophilus influenza type b, diphtheria, tetanus, and hepatitis B, both in donors and transplant recipients, produces high antibody titers in patients compared with recipient vaccination only. Because transplant recipients are immunocompromised, live vaccines should be avoided with few exceptions. Transplant recipients should get inactive vaccinations when possible to prevent infection. This includes vaccination against influenza, pneumococcus, H. influenza type b, diphtheria, tetanus, pertussis, meningococcus, measles, mumps, rubella, polio, hepatitis A, human papillomavirus, and hepatitis B. Close contacts of transplant recipients can safely get vaccinations (inactive and few live vaccines) as per their need and schedule. Transplant recipients who wish to travel may need to get vaccinated against endemic diseases that are prevalent in such areas. There is paucity of data on the role of vaccinations for patients receiving novel immunotherapy such as bispecific antibodies and chimeric antigen receptor T cells despite data on prolonged B cell depletion and higher risk of opportunistic infections.