Objective The objective of this study was to examine the religious/spiritual beliefs of followers of the five major world religions about frequently encountered medical situations at the end of life (EoL). Method This was a systematic review of observational studies on the religious aspects of commonly encountered EoL situations. The databases used for retrieving studies were: Ovid MEDLINE In-Process & Other Non-Indexed Citations, Ovid MEDLINE, Ovid EMBASE, Ovid PsycINFO, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus. Observational studies, including surveys from healthcare providers or the general population, and case studies were included for review. Articles written from a purely theoretical or philosophical perspective were excluded. Results Our search strategy generated 968 references, 40 of which were included for review, while 5 studies were added from reference lists. Whenever possible, we organized the results into five categories that would be clinically meaningful for palliative care practices at the EoL: advanced directives, euthanasia and physician-assisted suicide, physical requirements (artificial nutrition, hydration, and pain management), autopsy practices, and other EoL religious considerations. A wide degree of heterogeneity was observed within religions, depending on the country of origin, level of education, and degree of intrinsic religiosity. Significance of results Our review describes the religious practices pertaining to major EoL issues and explains the variations in EoL decision making by clinicians and patients based on their religious teachings and beliefs. Prospective studies with validated tools for religiosity should be performed in the future to assess the impact of religion on EoL care.

Chemotherapy-induced thrombocytopenia (CIT) frequently complicates cancer treatment causing chemotherapy delays, dose reductions, and discontinuation. There is no FDA-approved agent available to manage CIT. This study retrospectively evaluated patients with CIT treated on institutional romiplostim treatment pathways at 4 U.S. centers. The primary outcome was achievement of a romiplostim response [median on-romiplostim platelet count (Plt) ≥75x109/L and ≥30x109/L above baseline]. Secondary outcomes included time to Plt≥100x109/L and rates of the following: Plt<100x109/L, Plt<75x109/L, Plt<50x109/L, thrombocytosis, chemotherapy dose reduction/treatment delay, platelet transfusion, bleeding, and thromboembolism. Multivariable regression was used to identify predictors of romiplostim non-response and compare weekly dosing with intracycle/intermittent dosing. 173 patients (153 solid tumor, 20 lymphoma or myeloma) were treated, with 170 (98%) receiving a median of 4 (range, 1-36) additional chemotherapy cycles on romiplostim. Romiplostim was effective in solid tumor patients: 71% of patients achieved a romiplostim response, 79% avoided chemotherapy dose reductions/treatment delays and 89% avoided platelet transfusions. Median per-patient Plt on romiplostim was significantly higher than baseline (116x109/L vs. 60x109/L, P<0.001). Bone marrow tumor invasion, prior pelvic irradiation, and prior temozolomide predicted romiplostim non-response. Bleeding rates were lower than historical CIT cohorts and thrombosis rates were not elevated. Weekly dosing was superior to intracycle dosing with higher response rates and less chemotherapy dose reductions/treatment delays (IRR 3.00, 95% CI 1.30-6.91, P=0.010) or bleeding (IRR 4.84, 95% CI 1.18-19.89, P=0.029). Blunted response (10% response rate) was seen in non-myeloid hematologic malignancy patients with bone marrow involvement. In conclusion, romiplostim was safe and effective for CIT in most solid tumor patients.

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Debridement is an essential component of wound care as the presence of devitalised tissue can impede the healing process. Larval therapy has been used for the debridement of wounds for several hundred years. A plethora of literature is available on larval therapy, but many authors acknowledge the paucity of large-scale clinical trials supporting its effectiveness. While the exact mechanism of larval therapy remains unknown, it encompasses three processes: debridement, disinfection and promotion of healing. This literature review discusses the applications, benefits and disadvantages of larval therapy as well as the processes involved. The literature reviewed suggests that further comprehensive research into the mechanisms involved in larval therapy is required to ensure that it may be used to best medical advantage.

Background Acquired hemophilia A is a rare bleeding disorder caused by autoantibodies that inhibit coagulation factor VIII (FVIII). The disorder is understudied given its rarity and there are no randomized prospective trials to guide therapy. In practice, treatment involves attaining hemostasis and eliminating the FVIII inhibitor, typically with high-dose steroids (1 mg/kg daily) and either cyclophosphamide or rituximab. However, current approaches carry risk of significant adverse events and delayed or inadequate responses. Emicizumab is a bispecific antibody that targets coagulation factors IXa and X to recapitulate the function of endogenous FVIII. We present a case series of patients with acquired hemophilia A who were successfully treated with a regimen consisting of rituximab and emicizumab. Methods We identified patients &gt;18 years who were diagnosed with acquired hemophilia A and received treatment with rituximab and emicizumab at Brigham and Women's Hospital between 2019 and 2020. We performed a retrospective chart review. Data collected included the patients' clinical presentation, laboratory studies (including coagulation testing, FVIII activity, and FVIII inhibitor titer), and treatments received (including systemic therapies, recombinant factor VIIa [rFVIIa], red blood cell [RBC] transfusions, and vascular embolization). We recorded the time to normalization of the activated partial thromboplastin time (aPTT) and chromogenic FVIII activity following emicizumab and rituximab initiation, respectively. Activated prothrombin complex concentrate was avoided given the use of emicizumab. Results We identified 8 patients with acquired hemophilia A who received treatment with emicizumab and rituximab. The median patient age was 81 (range 47-93). All patients sought medical attention for extensive ecchymoses or bleeding and were found to have prolonged aPTT leading to FVIII inhibitor identification (Table 1). The median inhibitor titer was 18 Bethesda units (range 9.2-107.5). Patients concurrently received 4 weekly doses of rituximab 375mg/m2 and 4 weekly loading doses of emicizumab 3mg/kg. Patient (Pt) #1 continued emicizumab 3mg/kg every two weeks to complete three months of treatment. Pts #2, #3, and #8 received high-dose prednisone (1mg/kg) at the start of treatment for a range of 10-14 days. Pt #8 received 7 additional days of prednisone for an initial aPTT of 60.7 seconds before starting emicizumab and rituximab; she had no clinical response when treated with prednisone alone. Pts #2, #5, and #7 required vascular embolization. 7 patients (Pts #2 through #8) had aPTT retested within 1 week of starting emicizumab, and the aPTT for these patients normalized within 10 days of starting emicizumab (i.e. after only 1-2 doses; Figure 1). Except for Pt #5 who had recurrent hematuria from a persistent anatomic bladder defect that eventually required prostatic artery embolization, patients did not require rFVIIa or RBC transfusions for more than 7 days after starting emicizumab. Except for Pt #5 who required 28 doses of rFVIIa and 3 units of RBC transfusions after starting emicizumab, the median number of rFVIIa doses and RBC units given to the remaining 7 patients was zero (range 0-6 doses) and zero (range 0-4 units), respectively. Pts #2 and #3 had chromogenic FVIII levels obtained &gt;30 days after starting rituximab with improvement in FVIII activity to 29% (day 71) and 86% (day 91), respectively. During a median follow-up of 102 days, no patients experienced recurrent bleeding. However, Pt #3 exhibited a slowly increasing aPTT that reached 46.3 seconds on day 233 of follow-up without symptoms; further diagnostic testing is pending. Conclusion Our case series demonstrates that the combination of rituximab and emicizumab can be an effective and safe regimen for the treatment of acquired hemophilia A. No thrombotic events or thrombotic microangiopathy occurred. Treatment with weekly emicizumab led to aPTT normalization after 1-2 doses and facilitated hemostasis, as reflected by a median usage of zero rFVIIA doses and zero RBC transfusions after starting emicizumab when excluding one patient with hematuria from an anatomic defect. This compares favorably to historical reports. While no patient has had recurrent bleeding, additional chromogenic FVIII activity testing for patients is needed to confirm long-term normalization of FVIII activity. Disclosures Gibson: Ampressa therapeutics: Current equity holder in private company; nference: Consultancy, Current equity holder in private company; ImmPACT-Bio: Consultancy; Boston Clinical Research Institute: Consultancy. Parnes:Bayer: Consultancy; I-Mab: Consultancy; Sunovion: Consultancy; UniQure: Consultancy; Sigilon: Consultancy; Shire/Takeda: Consultancy, Research Funding; Genentech: Research Funding; Geron: Current equity holder in publicly-traded company. OffLabel Disclosure: Emicizumab is used off-label in our case series for the treatment of acquired hemophilia A.

Summary Overexpression of pro-inflammatory cytokines, including tumour necrosis factor alpha (TNFα), has been implicated in the pathogenesis of anaemia of inflammation. TNFα suppresses erythroid colony formation via both direct and indirect effects on haematopoietic progenitors, often involving activation of nuclear factor (NF)-κB signalling resulting in downregulation of transcription factors critical for erythropoiesis. There is a dearth of effective and safe therapies for many patients with inflammatory anaemia. Resveratrol is a flavanol found in red wine grapes that possesses potent anti-inflammatory properties, but studies of its impact on human erythropoiesis have proven contradictory. We investigated whether resveratrol ameliorates TNFα-mediated suppression of erythropoiesis in human CD34+ haematopoietic progenitors. We found that resveratrol partially reverses the erythroid suppressive effects of TNFα, leading to significant recovery in burst forming unit-erythroid colony formation in human CD34+ cells. CD34+ cells pre-incubated with resveratrol for 72 h in the presence of TNFα inhibited NF-κB activation via decreased NF-κB nuclear localization without altering total NF-κB protein levels and independent of IκB degradation. Resveratrol also significantly restored the baseline expression of erythroid transcription factors NFE2 and the GATA1/GATA2 ratio in CD34+ cells treated with TNFα. In conclusion, resveratrol may inhibit TNFα-mediated NF-κB activation and promote erythropoiesis in primary human CD34+ cells.

Therapy-related myeloid neoplasms are neoplastic processes arising as a result of chemotherapy, radiation therapy, or a combination of these modalities given for a primary condition. The disease biology varies based on the etiology and treatment modalities patients receive for their primary condition. Topoisomerase Ⅱ inhibitor therapy results in balanced translocations. Alkylating agents, characteristically, give rise to more complex karyotypes and mutations in p53. Other etiologies include radiation therapy, high-dose chemotherapy with autologous stem cell transplantation and telomere dysfunction. Poor-risk cytogenetic abnormalities are more prevalent than they are in de novo leukemias and the prognosis of these patients is uniformly dismal. Outcome varies according to cytogenetic risk group. Treatment recommendations should be based on performance status and karyotype. An in-depth understanding of risk factors that lead to the development of therapyrelated myeloid neoplasms would help developing riskadapted treatment protocols and monitoring patients after treatment for the primary condition, translating into reduced incidence, early detection and timely treatment.

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