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Summary: Although descriptions of quality of life and patient reports of mood in sickle cell disease (SCD) have become more common in the literature, less is known about psychiatric illness prevalence, presentation, and treatment, particularly for adults. We provide a narrative review of what is known about common and debilitating psychiatric conditions such as depression, anxiety, and cognitive impairment, specifically for adults with SCD. We discuss the limitations of the current evidence, make provisional recommendations, and identify opportunities for research and improved care. [ABSTRACT FROM AUTHOR]

Background: Hematopoietic cell transplantation (HCT) recipients have reduced antibody titers to tetanus, diphtheria, and pertussis. Tdap is approved for revaccinating adult HCT recipients in the United States, whereas DTaP is not approved in this population. To our knowledge, no studies to date have compared responses to DTaP versus Tdap in adult HCT patients. We conducted a retrospective study comparing responses to DTaP versus Tdap vaccines in otherwise similar adult HCT patients in order to determine if one of these vaccines elicits superior antibody responses. Methods: We evaluated 43 allogeneic and autologous transplant recipients as a combined cohort and as separate subsets for vaccine specific antibody titers and proportion of strong vaccine responders. Subset analysis focused on the autologous transplant recipients. Results: Higher median antibody titers were found to all vaccine components among DTaP recipients (diphtheria p =.021, pertussis p =.020, tetanus p =.007). DTaP recipients also had more strong responders to diphtheria and pertussis (diphtheria p =.002, pertussis p =.006). Among the autologous HCT recipient subset, there were more strong responders to diphtheria (p =.036). Conclusions: Our data shows that post‐HCT vaccination with DTaP leads to higher antibody titers and more strong responders, which suggests that DTaP is more effective than Tdap in HCT recipients. [ABSTRACT FROM AUTHOR]

Summary: Although Dara–VCD (daratumumab–bortezomib–cyclophosphamide–dexamethasone) has revolutionized the treatment of newly diagnosed Amyloid Light chain (AL) amyloidosis, patients with stage IIIb disease were excluded in the pivotal trial. We performed a multicentre retrospective cohort study to investigate the outcomes of 19 consecutive patients treated with Dara–VCD front‐line therapy who had stage IIIb AL at diagnosis. More than two thirds presented with New York Heart Association Class III/IV symptoms, and had a median of two organs involved (range, 2–4). The haematologic overall response rate was 100%, with 17/19 patients (89.5%) achieving a very good partial response (VGPR) or better. Haematologic responses were achieved rapidly, as evidenced by 63% of evaluable patients with involved serum free light chains (iFLC) < 2 mg/dl and the difference between involved and uninvolved serum free light chains (dFLC) <1 mg/dl at three months. Among 18 evaluable patients, 10 (56%) achieved a cardiac organ response and six (33%) cardiac VGPR or better. The median time to first cardiac response was 1.9 months (range, 0.4–7.3). At a median follow‐up of 12 months for surviving patients, estimated one‐year overall survival was 67.5% [95% confidence interval (CI), 43.8–84.7]. The incidence of grade 3 or higher infections was 21%, with no infection‐related mortality thus far. In summary, Dara–VCD has a promising efficacy and safety profile in stage IIIb AL, and should be studied in prospective trials. [ABSTRACT FROM AUTHOR]

Background: Cytomegalovirus (CMV) reactivation is associated with significant morbidity and mortality after an allogeneic hematopoietic cell transplant (AHCT), and graft versus host disease (GVHD) increases the risk of CMV reactivation. Letermovir is approved for CMV prophylaxis in CMV‐seropositive patients, but has only been studied through day 100 post‐transplantation in the registration trial. Its efficacy in preventing CMV in patients with GVHD requiring treatment beyond the day 100 milestone has not been studied. Methods: We retrospectively analyzed all patients who underwent an AHCT at a single center over a period of 24 months, and identified a cohort of 20 patients who received extended duration of letermovir (beyond 100 days) after the diagnosis of GVHD. The primary end point was the incidence of clinically significant CMV infection, defined as onset of CMV disease or initiation of preemptive therapy with alternative antiviral agents. Results: In this high‐risk cohort, only one patient (5%) developed a clinically significant CMV infection, requiring preemptive therapy. No patients developed CMV organ disease. Three additional patients developed CMV viremia of ≥150 IU/mL while on letermovir and after the onset of GVHD, and none required additional treatment. Receipt of post‐transplant cyclophosphamide (PTCy) and low CD4 count after the development of GVHD were associated with breakthrough CMV viremia while on extended duration letermovir. Conclusions: Extended duration letermovir was efficacious in preventing clinically significant CMV infections in patients with GVHD. [ABSTRACT FROM AUTHOR]

Over the past three decades, the increasing rates of obesity have led to an alarming obesity epidemic worldwide. Obesity is associated with an increased risk of cardiovascular diseases; thus, it is essential to define the molecular mechanisms by which obesity affects heart function. Individuals with obesity and overweight have shown changes in cardiac structure and function, leading to cardiomyopathy, hypertrophy, atrial fibrillation, and arrhythmia. Autophagy is a highly conserved recycling mechanism that delivers proteins and damaged organelles to lysosomes for degradation. In the hearts of patients and mouse models with obesity, this process is impaired. Furthermore, it has been shown that autophagy flux restoration in obesity models improves cardiac function. Therefore, autophagy may play an important role in mitigating the adverse effects of obesity on the heart. Throughout this review, we will discuss the benefits of autophagy on the heart in obesity and how regulating autophagy might be a therapeutic tool to reduce the risk of obesity-associated cardiovascular diseases. [ABSTRACT FROM AUTHOR]

The article focuses on the impact of brentuximab vedotin and bendamustine in patients with chemotherapy refractory Hodgkin lymphoma (HL) in monotherapy. It mentions salvage therapies include ifosfamide, carboplatin and etoposide and followed by autologous stem cell transplant (ASCT) and treated on the aforementioned clinical trial. It also mentions patients underwent positron emission tomography and computed tomography imaging to assess response.

Abstract: Mitogen‐activated protein kinase (MAPK) signaling has been dysregulated in different types of cancers. However, targeting MAPK signaling with small molecules leads to severe toxic side effects to the patients as well as manifestation of drug resistance. To address these, we have developed 120 nm sized self‐assembled, biocompatible, biodegradable oleic acid nanoparticles (OA‐NPs) which can simultaneously contain AZD6244 (MAPK inhibitor) and cisplatin (DNA damaging drug). These OA‐NPs released AZD6244 and cisplatin in increased amount in pH 5.5 compared to pH 7.4 in a slow and sustained manner over 4 days with excellent stability at 4 °C for 2 months in water and in blood circulation mimic for 6 days. Moreover, these OA‐NPs showed much improved in vitro cytotoxicity in cervical cancer (HeLa) and triple negative breast cancer (MDA‐MB‐231) cells at 48 h and in hepatocellular carcinoma (Hep3B) and cisplatin‐resistant hepatocellular carcinoma (Hep3B‐R) cells at 24 h. In HeLa cells, these OA‐NPs induced apoptosis through inhibiting MAPK signaling and damaging DNA after being internalized through macropinocytosis and homed into the acidic lysosomal compartments. These OA‐NPs have the potential to be translated into the clinic for targeting multiple oncogenic signaling pathways and damaging DNA concurrently for augmented efficacy, reduced toxicity, and overcoming drug resistance in next‐generation cancer treatment. [ABSTRACT FROM AUTHOR]

Background and Aim Proton pump inhibitors ( PPI) and H2-receptor antagonists (H2RA) are frequently prescribed in hospitalized patients with cirrhosis. There are conflicting reports regarding the role of acid-suppressive therapy in predisposing hospitalized patients with cirrhosis to spontaneous bacterial peritonitis ( SBP). The aim of this meta-analysis was to evaluate the association between acid-suppressive therapy and the risk of SBP in hospitalized patients with cirrhosis. Methods We searched MEDLINE and four other databases for subject headings and text words related to SBP and acid-suppressive therapy. All observational studies that investigated the risk of SBP associated with PPI/ H2RA therapy and utilized SBP as an endpoint were considered eligible. Data from the identified studies were combined by means of a random-effects model and odds ratios ( ORs) were calculated. Results Eight studies ( n = 3815 patients) met inclusion criteria. The risk of hospitalized cirrhotic patients developing SBP increased when using acid-suppressive therapy. The risk was greater with PPI therapy ( n = 3815; OR 3.15, 95% confidence interval 2.09-4.74) as compared to those on H2RA therapy ( n = 562; OR 1.71, 95% confidence interval 0.97-3.01). Conclusions Pharmacologic acid suppression was associated with a greater risk of SBP in hospitalized patients with cirrhosis. Cirrhotic patients receiving a PPI have approximately three times the risk of developing SBP compared with those not receiving this medication. Prospective studies may help clarify this relationship and shed light on the mechanism(s) by which acid-suppressive therapy increases the risk of SBP in hospitalized patients with cirrhosis. [ABSTRACT FROM AUTHOR]

Background: With improvements in the care of critically ill, physicians are faced with obligations to provide quality end-of-life care. Barriers to this include inadequate understanding of the dying patient and withdrawal or limitation of care. The objectives of this study were to document the comprehensions of physicians and nurses regarding the recognition and practice of end-of-life care for critically ill patients placed on life support in the intensive care unit. Methods: This was a cross-sectional study carried out at three hospitals in Karachi. Chi-squared analysis and one-wayanova were used to compare differences in response between the groups. Results: One hundred and thirty-seven physicians and critical care nurses completed the survey. ‘Brain death’ was defined as an ‘irreversible cessation of brainstem function’ by 85% respondents, with 50% relying on specialty consultation. Withdrawal of life support is practised by 83.2%; physicians are more likely (Chi square test P-value < 0.001) to withdraw mechanical ventilation, compared with nurses who would withdraw vasopressors ( P-value 0.006). In a do not resuscitate patient, 72.3% use vasopressors, 83% initiate haemodialysis and 17.5% use non-invasive ventilation; 72.6% consult Hospital Ethics Committees; 16% respondents never withdraw life support; 28.3% considered it their responsibility to ‘sustain life at all costs’ and only 8% gave religious beliefs as a reason. Conclusions: There are confusions in the definition of brain death, end-of-life recognition and indications and processes of withdrawal of life support. There are discrepancies between physicians’ and nurses’ perceptions and attitudes. Clearly, teaching programmes will need to incorporate cultural and religious differences in their ethics curricula. [ABSTRACT FROM AUTHOR]

Clinical trials have shown the high anti-myeloma activity of the proteasome inhibitor bortezomib. The present study examined the activity of bortezomib combined with PXD101, a histone deacetylase inhibitor, against multiple myeloma (MM) and osteoclastogenesis. Treatment of myeloma cell lines with combinations of bortezomib and PXD101 led to synergistic inhibition of proliferation and induction of cell death. The combination significantly decreased the viability of primary human CD138+ myeloma cells but not of bone marrow mononuclear cells. Further studies showed a dose-dependent activation of caspases-3, -8 and -9 and nuclear fragmentation in myeloma cells. Bortezomib/PXD101 treatment markedly triggered reactive oxygen species (ROS) generation that was accompanied by p53, H2A.X and p38–mitogen-activated protein kinase phosphorylation. ROS generation could be blocked by the free radical scavenger N-acetyl-l-cysteine. The combination of bortezomib and PXD101 also resulted in synergistic inhibition of osteoclast formation. In conclusion, bortezomib and PXD101 have different molecular targets. The combination induces cell death in myeloma cells via ROS-mediated DNA damage and also inhibits osteoclastogenesis. Therefore, this study provides the rationale for the clinical evaluation of bortezomib combined with PXD101 in patients with MM. [ABSTRACT FROM AUTHOR]