Effects of corticosteroids in patients with sickle cell disease and acute complications: a systematic review and meta-analysis

Whether corticosteroids improve outcome in patients with acute complications of sickle cell disease (SCD) is still debated. We performed a systematic review of the literature with the aim of estimating effects of corticosteroids on the clinical course of vaso-occlusive crisis (VOC) or acute chest syndrome (ACS) in patients with SCD. The primary outcome was transfusion requirement during hospitalization. Studies were identified by search of MEDLINE and CENTRAL database. Three randomized clinical trials (RCT) and three retrospective cohort studies (RCS) were included, involving 3,304 participants and 5,562 VOC or ACS episodes. There was no difference between corticosteroids and standard treatment regarding transfusion overall [OR=0.98 (95% CI 0.38 to 2.53)], but with a significant interaction of study type (P

Estimation of Coronavirus Disease 2019 Hospitalization Costs From a Large Electronic Administrative Discharge Database, March 2020–July 2021

Background Information on the costs of inpatient care for patients with coronavirus disease 2019 (COVID-19) is very limited. This study estimates the per-patient cost of inpatient care for adult COVID-19 patients seen at >800 US hospitals. Methods Patients aged ≥18 years with ≥1 hospitalization during March 2020–July 2021 with a COVID-19 diagnosis code in a large electronic administrative discharge database were included. We used validated costs when reported; otherwise, costs were calculated using charges multiplied by cost-to-charge ratios. We estimated costs of inpatient care per patient overall and by severity indicator, age, sex, underlying medical conditions, and acute complications of COVID-19 using a generalized linear model with log link function and gamma distribution. Results The overall cost among 654673 patients hospitalized with COVID-19 was $16.2 billion. Estimated per-patient hospitalization cost was $24 826. Among surviving patients, estimated per-patient cost was $13 090 without intensive care unit (ICU) admission or invasive mechanical ventilation (IMV), $21 222 with ICU admission alone, and $59 742 with IMV. Estimated per-patient cost among patients who died was $27 017. Adjusted cost differential was higher among patients with certain underlying conditions (eg, chronic kidney disease [$12 391], liver disease [$8878], cerebrovascular disease [$7267], and obesity [$5933]) and acute complications (eg, acute respiratory distress syndrome [$43 912], pneumothorax [$25 240], and intracranial hemorrhage [$22 280]). Conclusions The cost of inpatient care for COVID-19 patients was substantial through the first 17 months of the pandemic. These estimates can be used to inform policy makers and planners and cost-effectiveness analysis of public health interventions to alleviate the burden of COVID-19.

Comparison of radiotherapy combined with nimotuzumab vs. chemoradiotherapy for locally recurrent nasopharyngeal carcinoma

Background The present study compared the effectiveness and toxicity of two treatment modalities, namely radiotherapy combined with nimotuzumab (N) and chemoradiotherapy (CRT) in patients with locally recurrent nasopharyngeal carcinoma (LR-NPC). Methods Patients with LR-NPC who were treated with radiotherapy were retrospectively enrolled from January 2015 to December 2018. The treatment included radiotherapy combined with N or platinum-based induction chemotherapy and/or concurrent chemotherapy. The comparison of survival and toxicity between the two treatment modalities was evaluated using the log-rank and chi-squared tests. Overall survival (OS) was the primary endpoint. Results A total of 87 patients were included, of whom 32 and 55 were divided into the N group and the CRT group, respectively. No significant differences were noted in the survival rate between the N and the CRT groups (4-year OS rates, 37.1% vs. 40.7%, respectively; P = 0.735). Mild to moderate acute complications were common during the radiation period and mainly included mucositis and xerostomia. The majority of the acute toxic reactions were tolerated well. A total of 48 patients (55.2%) demonstrated late radiation injuries of grade ≥ 3, including 12 patients (37.5%) in the N group and 36 patients (66.5%) in the CRT group. The CRT group exhibited significantly higher incidence of severe late radiation injuries compared with that of the N group (P = 0.011). Conclusion Radiotherapy combined with N did not appear to enhance treatment efficacy compared with CRT in patients with LR-NPC. However, radiotherapy combined with N may be superior to CRT due to its lower incidence of acute and late toxicities. Further studies are required to confirm the current findings.

Severe Acute Complications of Sickle Cell Disease in Two Expert Referral Centers (UK and Italy): Natural History Studies Highlight Ongoing Unmet Need for Effective Disease Modifying or Curative Therapies

Background: Hydroxyurea (HU) and chronic transfusion therapy (CTT) are the only disease modifying therapies (DMTs) currently available as standard of care in the UK and Italy for patients with sickle cell disease (SCD), with hematopoietic stem cell transplant (HSCT) available to a small fraction of patients. Few registries capture long-term follow up of real-world outcomes among patients with SCD and there is a need for natural history studies demonstrating morbidity and mortality under existing standard of care. The East London Newborn Sickle Cohort Study (ELNSCS) at the Royal London Hospital and the Sickle Cell Disease Cohort (SCDC) at the University of Padova (UNIPD) collect biomarker and clinical data on patients followed comprehensively at two expert referral centers and provide an opportunity to understand SCD real-world outcomes. Here, we report severe acute complications under standard of care during years when HU and CTT were widely available and accepted. Methods: Inclusion of patients in the ELNSCS required being born in a designated region in London, diagnosed by newborn screening between 1983-2018 and, for this analysis, followed during 2015-2018. Inclusion in the SCDC required being followed, for this analysis, at the UNIPD during 2016-2019. Analyses were restricted to patients with β Sβ S, β Sβ 0, and, for ELNSCS, β Sβ +. Data were entered into clinical databases at each site and subsequently validated against institutional records. Severe vaso-occlusive events (VOEs) were defined as events requiring admission (inpatient, ED, or hematology day unit) for acute chest syndrome (ACS), acute painful crisis, acute hepatic/splenic sequestration, acute ischaemic stroke, dactylitis and priapism. Statistical analysis was aligned between both sites. Patients were categorized into three mutually exclusive treatment groups (HU, CTT, no treatment) according to treatment during study period. Results: One hundred seventy-two patients in the ELNSCS and 62 patients at UNIPD met study inclusion criteria in the four-year analysis period. HbSS genotype accounted for 161 (93.6%) of ELNSCS cohort and 58 (93.5%) of UNIPD cohort. Median age at study entry was 11.6 (range 0.2 - 31.4) years in the ELNSCS and 7.66 (range 0.12 - 19.96) years at UNIPD. Median age differed across treatment groups; HU group tended to be younger, while CTT group tended to be older. According to institutional standards of care, 47 (27.3%) patients from the ELNSCS and 50 (80.6%) from UNIPD received HU, 53 (30.8%) from the ELNSCS and 8 (12.9%) from UNIPD received CTT, and 72 (41.9%) from the ELNSCS and 4 (6.5%) from UNIPD received no treatment during the four year study period. Differences in treatment allocation reflect slightly different patient populations and approaches to care at the two centers. Severe VOEs persist among patients in all three treatment groups at both sites. Of those receiving HU, 83.0% from the ELNSCS and 68.0% at UNIPD had ≥1 severe VOE, including 21.3% from the ELNSCS and 44.0% at UNIPD experiencing ≥1 ACS event. The rate of severe VOEs in the HU group was 0.75 (range 0 - 39.5) per patient year from the ELNSCS and 0.49 (range 0 - 3.00) per patient year from UNIPD. HU dosing and adherence will be explored using data collected on hematologic parameters. In the ELNSCS, of those receiving CTT, 60.4% experienced ≥1 severe VOE (20.8% had ≥1 ACS event); of those receiving no therapy, 56.9% experienced ≥1 severe VOE (11.1% had ≥1 ACS event). At UNIPD, severe VOEs were observed in 62.5% of the CTT group and 50% of the no treatment group, though sample sizes were very small. C onclusions: Despite receiving expert care in accordance with local and international guidelines at two large academic centers, a significant sub-group of patients continue to experience severe VOEs. Results show that real-world usage of HU and CTT may not be optimized and, even if optimized, some patients may continue to experience severe acute complications including ACS. Both cohorts confirm that implementation of existing standard of care is insufficient to prevent significant morbidity in patients with SCD. Findings suggest the need to introduce DMT early in life to reduce and prevent acute complications and minimize disease progression. There is a persistent need for maximizing effective DMTs, as well as further developing curative therapies such as HSCT and gene therapy for both pediatric and adult patients. Figure 1 Figure 1. Disclosures Colombatti: Novartis: Membership on an entity's Board of Directors or advisory committees; Novo Nordisk: Membership on an entity's Board of Directors or advisory committees; Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; BlueBirdBio: Membership on an entity's Board of Directors or advisory committees, Research Funding. Chawla: BlueBirdBio: Current Employment. Puri-Sharma: BlueBirdBio: Current Employment. Walls: BlueBirdBio: Current Employment. Kommera: BlueBirdBio: Current Employment. Telfer: Novo Nordisk: Membership on an entity's Board of Directors or advisory committees; Emmaus: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Addmedica: Membership on an entity's Board of Directors or advisory committees; ApoPharma: Membership on an entity's Board of Directors or advisory committees; Global Blood Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BlueBirdBio: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Terumo: Honoraria; Roche: Membership on an entity's Board of Directors or advisory committees.

Complement Activation during Vaso-Occlusive Pain Crisis in Pediatric Sickle Cell Disease

Background: Sickle cell disease (SCD) affects millions of individuals worldwide with substantial morbidity and mortality. The sickle hemoglobin (HbS) polymerizes upon deoxygenation, causing rigid and adhesive red blood cells (RBCs), triggering vascular occlusion, greatly shortened RBC lifespan, and chronic hemolysis. Amongst acute complications in SCD, vaso-occlusive pain crisis (VOC) is the leading cause of hospitalization, with supportive care being the primary approach to management. We and others have recently demonstrated important contributions of complement to the pathophysiology of SCD. When the complement pathway (CP) is activated during SCD crises, inhibition at C5 using eculizumab, has been successful in treating various acute complications in SCD (Chonat et al, Haematologica). In this study, we prospectively analyzed the extent of CP activation among children with SCD presenting with VOC. Methods: Patients aged 0-21 years old managed at Children's Healthcare of Atlanta with homozygous sickle cell (SS) or S beta zero thalassemia genotypes were enrolled in an IRB-approved research study. Inclusion criteria included those requiring intravenous opioids for VOC, and excluded those with chronic pain, >6 VOC admission in the previous 12 months or on chronic transfusions. Blood samples were collected within 48 hours of VOC presentation, and steady-state levels were obtained at a 4-week clinic follow-up. Data was analyzed using a paired t-test, and receiver operator characteristic (ROC) curves were generated comparing intra-person complement levels during acute VOC versus respective steady-state levels. Results: Sixty-four patients have been enrolled thus far, of which 43 (67%) had steady-state samples collected. The majority of patients (90.5%) have SS genotype with a mean (SD) patient age of 14.15 (4.68) years. Fifty-three (84.1%) patients reported taking hydroxyurea (HU). Fifty-nine (93.7%) patients had at least one VOC admission in the past 12 months, with an average of 2.98 (1.67) VOC admissions. Pain Score reported on 55 patients averaged 4.93 (4.78) on a pain scale of 0 to 10. Mean values during VOC and steady-state of hemoglobin (Hb) were 8.12 and 9.01 g/dL, platelet count 431 and 511, and lactate dehydrogenase (LDH) 549 and 483 U/L, respectively. Seventeen patients had complement work-up performed during acute and steady-state, and 4 of them had additional samples collected during subsequent VOC. Complement protein levels C3, C4, C5, properdin, factor B, and complement regulatory proteins factor H and I were unremarkable during VOC and steady-state. However, complement activation markers, specifically anaphylatoxins C3a, C5a and Bb were significantly elevated during VOC compared to steady-state (see Table 1) suggesting activation of alternative CP during VOC (see Table 1 and Figure 1A-C). Terminal complement complex (C5b9) was not statistically different between VOC and steady-state (Figure 1D, red dotted lines signify normal ranges). Remarkably, patients who re-presented with acute VOC exhibited similar increases in their C3a/C5a (Figure 1E-F), substantiating the increases related to their VOC. Hemoglobin and LDH (Figure 1G-H) were similarly significant, suggestive of intravascular hemolysis. Three (7.1%) patients developed acute chest syndrome, two of whom experienced respiratory failure requiring intensive care management, and all exhibited significant CP activation. The area under the curve (AUC) of the ROC curve was analyzed to determine the ability of complement biomarkers to differentiate VOC from steady-state. Based on the AUC of these biomarkers, complement anaphylatoxins C3a and C5a exhibited the highest AUC of 0.76 and 0.87, respectively. Discussion: To our knowledge, this is the first prospective and comprehensive evaluation of CP in patients with SCD during VOC and steady-states. These preliminary findings suggest CP activation is present in a large proportion of patients during VOC, with increased activation of alternative and common CP, associated with intravascular hemolysis. Minimal increase in C5b9 could be explained by a significant proportion (> 80%) of our patients being on HU therapy, similar to prior data (Roumenina et al, AJH). Specifically, C3a/C5a, along with other biomarkers, could not only predict disease activity in patients during VOC, but provide pharmacological targets in VOC, which need further validation. Figure 1 Figure 1. Disclosures Stowell: Alexion: Consultancy; Argenx: Speakers Bureau; Grifols: Speakers Bureau. Chonat: Alexion: Consultancy, Research Funding; Agios: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Global Blood Therapeutics: Consultancy, Research Funding; Takeda: Consultancy, Research Funding.

Pancreaticobiliary Malignancies in the Emergency Room: Management of Acute Complications and Oncological Emergencies

Background Management of pancreaticobiliary (PB) malignancies remains a clinical challenge. In this review, we focus on the management of oncological emergencies in PB malignancies and the potential complication of associated therapeutic interventions. Methods Biobliographic review of current evidence on the management of oncological emergencies, their potential complications, as well as synthesis of recommendations was performed. The pathogenesis, frequency, related symptoms as well as appropriate investigations are presented. Results The oncologic emergencies in PB patients were summarised in six categories: (1) hematological (including febrile neutropaenia, thrombocytopenia, coagulopathies), (2) gastrointestinal (gastric outlet and biliary obstruction, gastrointestinal bleeding), (3) thromboembolic events, (4) ascites, (5) metabolic disorders and (6) neurologic complications. The pathogenesis, frequency, related symptoms as well as appropriate investigations are also presented. Conclusion Patients with PB malignancies are at increased risk of a wide variation of medical emergencies. Clinical knowledge, early recognition and collaboration with the relevant specialties are critical to manage these complications effectively, tailoring overall management around the actual prognosis and individuals’ expectations.

Recurrent pericarditis is less scary: the new therapeutic solutions

Pericarditis is a common inflammatory disease affecting the pericardial sac, resulting from a variety of stimuli that trigger a stereotyped immune response. Generally self-limiting, this condition can be burdened by a significant risk of acute complications and relapses, with recurrence rates affecting up to 30% of patients, especially in the case of diagnostic and therapeutic delay. Therapeutic options in recurrent forms, initially based only on the use of traditional drugs such as colchicine, non-steroidal anti-inflammatory drugs, and corticosteroids, have recently been enriched with new molecules, such as interleukin 1 blockers anakinra and rilonacept, particularly indicated in refractory forms dependent on corticosteroids. Other medically relevant therapeutic possibilities in refractory disease include azathioprine, methotrexate, and intravenous immunoglobulins. This brief review aims to summarize the treatment strategies of recurrent pericarditis in light of the most up-to-date evidence and recommendations.

Insights on clinical outcomes in according to age in patients undergoing Transcatheter Aortic Valve Replacement

Transcatheter Aortic Valve Replacement (TAVR) is considered the treatment in patients older or at high or intermediate risk. Results form contemporary randomized trials in low-risk patients will likely broaden the indication of TAVR, but the data regarding long-term are limited by older population. The aim of this study was to evaluate the survival and the factors predicting mortality after TAVR in according to age. Methods From April 2008 to December 2019, the self-expandable and balloon-expandable prostheses were was implanted in 765 patients with symptomatic severe aortic stenosis with deemed high risk on base to age, <80 years and ≥80 years old. The rate of acute complications was defined by the combined endpoint of death, vascular complications, myocardial infarction, majopr bleeding or stroke. Results The mean age in patients <80 compared with ≥80 years, was 73.69±6.5 vs. 83.4±2.1 years and the logistic EuroSCORE and STS score were 15.9±11% vs. 18±11%, 4.8±3 vs. 6.3±4, p>0.001, respectively In-hospital mortality was 4% vs. 3.4%, p=0.404, and the rate of acute complications was 19.6 vs. 16.5%, p=0.168. The late mortality (beyond 30 days) was 36.9 vs. 35.2%, p=0.352. When compared in both groups, there were no differences for the presence of threatening bleeding 3.4% vs. 3.2% (HR = 1.028 [IC95% 0.722–1.463], p=0.516), myocardial infarction 4% vs. 2.5% (HR = 1.263 [IC95% 0.814–1.960], p=0.167), stroke 8% vs. 9.1% (HR = 1.149 [IC95% 0.686–1.925], p=0.347) and acute kidney innjury 14.1% vs. 19.1% (HR=0.1.14 [IC95% 0.969–2.141], p=0.071) and there was difference in between groups in hospitalizations for heart failure 14.6% vs. 7.9% (HR = 1.398 [IC95% 1.075–1.817], p=0.008 Survival at 1, 3, and 5were similar in both groups (88% vs. 89.5%, 73.3 vs. 78.2%, 58.8 vs. 62.6%, log Rank 0.992, p=0.319), respectively, after a mean follow-up of 42.3±27 months. The main predictors of cumulative mortality in young patients were: Charlson index [HR 1.18 (95% CI 1.06–1.30), p=0.001], Acute Kidney Injury [HR 2.21 (95% CI 1.42–3.47), p=0.001], Left ventricular ejection fraction [HR 1.02 (95% CI 1.009–1.035), p=0,001], and protective factor was a higher Karnosfky index [HR 0.98 (95% CI 0.97–0.99) p=0.006]. And in older patients were: Frailty [HR 1.67 (95% CI 1.13–2.47), p=0.010], COPD [HR 2.09 (95% CI 1.41–2.91), p=0,001], Stroke [HR 3.01 (95% CI 1.54–5.89), p=0.001] Charlson index [HR 1.14 (95% CI 1.02–1.27), p=0.015], Acute Kidney Injury [HR 1.57 (95% CI 1.06–2.32), p=0.001. Conclusions TAVR is associated with low complications rate in young and older patients. Survival during follow-up was similar in both groups, but the predictive factors of mortality differ, with greater impact on the comorbidtiy in the elderly patients FUNDunding Acknowledgement Type of funding sources: None.

Exposure To Cytotoxic Drugs Threatens The Health Of Staff In Oncology Wards

Background — Cancer is one of the leading causes of death worldwide. Using cytotoxic drugs for cancer treatment is increased. The hazardous effects of occupational exposure to cytotoxic drugs are challenging. Objective — This study aimed to compare the frequency of adverse effects and using personal protective equipment (PPE) between the staff of oncology wards and other hospital wards staff in Iran. Methods — A cross-sectional study with a control group was conducted on female staff members in educational hospitals, selected through convenience sampling. A data collection form was designed for this study. It includes demographic data, acute complications (allergic and neurologic reactions), chronic complications (infertility, menstrual disorders, malignancy, and congenital malformations), and use of PPE. Data analysis was performed using SPSS software through Chi-square and Mann-Whitney tests. Results — The frequencies of chronic complications were not statistically different between the two groups. The frequency of itching (P=0.001), hair loss (P=0.003), itchy eyes (P=0.001), watery eyes (P=0.001), runny nose (P=0.003), headache (P=0.001), vertigo (P=0.007), and nausea (P=0.008) were significantly higher in oncology wards nurses. Among different PPE, only the frequency of using the mask (P= 0.001), and glasses (P=0.027) were significantly higher in the staff of oncology wards. Conclusion — Despite the frequency of acute complications of exposure to cytotoxic drugs, oncology staff does not fully adhere to the standard precautions. Providing effective training and emphasis on implementing accreditation laws can improve the existing situation.

Direct-to-implant breast reconstruction following nipple-sparing mastectomy: predictive factors of adverse surgical outcomes in Asian patients

Background Direct-to-implant (DTI) breast reconstruction after nipple-sparing mastectomy (NSM) with the use of acellular dermal matrix (ADM) provides reliable outcomes; however, the use of ADM is associated with a higher risk of complications. We analyzed our experiences of post-NSM DTI without ADM and identified the predictive factors of adverse surgical outcomes.Methods Patients who underwent NSM and immediate DTI or two-stage tissue expander (TE) breast reconstruction from 2009 to 2020 were enrolled. Predictors of adverse endpoints were analyzed.Results There were 100 DTI and 29 TE reconstructions. The TE group had a higher rate of postmastectomy radiotherapy (31% vs. 11%; P=0.009), larger specimens (317.37±176.42 g vs. 272.08±126.33 g; P=0.047), larger implants (360.84±85.19 g vs. 298.83±81.13 g; P=0.004) and a higher implant/TE exposure ratio (10.3% vs. 1%; P=0.035). In DTI reconstruction, age over 50 years (odds ratio [OR], 5.43; 95% confidence interval [CI], 1.50–19.74; P=0.010) and a larger mastectomy weight (OR, 1.65; 95% CI, 1.08–2.51; P=0.021) were associated with a higher risk of acute complications. Intraoperative radiotherapy for the nipple-areolar complex increased the risk of acute complications (OR, 4.05; 95% CI, 1.07–15.27; P=0.039) and the likelihood of revision surgery (OR, 5.57; 95% CI, 1.25–24.93; P=0.025).Conclusions Immediate DTI breast reconstruction following NSM is feasible in Asian patients with smaller breasts.