Oral azacitidine modulates the bone marrow microenvironment in patients with acute myeloid leukaemia in remission: A subanalysis from the QUAZAR AML-001 trial.

Oral azacitidine (Oral-AZA) maintenance therapy improved relapse-free (RFS) and overall survival (OS) significantly versus placebo for AML patients in remission after intensive chemotherapy (IC) in the phase 3 QUAZAR AML-001 study. Immune profiling was performed on the bone marrow (BM) at remission and on-treatment in a subset of patients with the aim of identifying prognostic immune features and evaluating associations of on-treatment immune effects by Oral-AZA with clinical outcomes. Post-IC, increased levels of lymphocytes, monocytes, T cells and CD34 + CD117+ BM cells were prognostically favourable for RFS. CD3+ T-cell counts were significantly prognostic for RFS in both treatment arms. At baseline, high expression of the PD-L1 checkpoint marker was identified on a subset of CD34 + CD117+ BM cells; many of which were PD-L2+. High co-expression of T-cell exhaustion markers PD-1 and TIM-3 was associated with inferior outcomes. Oral-AZA augmented T-cell numbers during early treatment, increased CD4+:CD8+ ratios and reversed T-cell exhaustion. Unsupervised clustering analysis identified two patient subsets defined by T-cell content and expression of T-cell exhaustion markers that were enriched for MRD negativity. These results indicate that Oral-AZA modulates T-cell activity in the maintenance setting of AML, and these immune-mediated responses are associated with clinical outcomes.

Epidemiology of Acute Myocarditis/Pericarditis in Hong Kong Adolescents Following Comirnaty Vaccination.

BACKGROUND: Age-specific incidence of acute myocarditis/pericarditis in adolescents following Comirnaty vaccination in Asia is lacking. This study aimed to study the clinical characteristics and incidence of acute myocarditis/pericarditis among Hong Kong adolescents following Comirnaty vaccination. METHODS: This is a population cohort study in Hong Kong that monitored adverse events following immunization through a pharmacovigilance system for coronavirus disease 2019 (COVID-19) vaccines. All adolescents aged between 12 and 17 years following Comirnaty vaccination were monitored under the COVID-19 vaccine adverse event response and evaluation program. The clinical characteristics and overall incidence of acute myocarditis/pericarditis in adolescents following Comirnaty vaccination were analyzed. RESULTS: Between 14 June 2021 and 4 September 2021, 33 Chinese adolescents who developed acute myocarditis/pericarditis following Comirnaty vaccination were identified. In total, 29 (87.88%) were male and 4 (12.12%) were female, with a median age of 15.25 years. And 27 (81.82%) and 6 (18.18%) cases developed acute myocarditis/pericarditis after receiving the second and first dose, respectively. All cases are mild and required only conservative management. The overall incidence of acute myocarditis/pericarditis was 18.52 (95% confidence interval [CI], 11.67-29.01) per 100 000 persons vaccinated. The incidence after the first and second doses were 3.37 (95% CI, 1.12-9.51) and 21.22 (95% CI, 13.78-32.28 per 100 000 persons vaccinated, respectively. Among male adolescents, the incidence after the first and second doses were 5.57 (95% CI, 2.38-12.53) and 37.32 (95% CI, 26.98-51.25) per 100 000 persons vaccinated. CONCLUSIONS: There is a significant increase in the risk of acute myocarditis/pericarditis following Comirnaty vaccination among Chinese male adolescents, especially after the second dose.

Autoimmune gene expression profiling of fingerstick whole blood in Chronic Fatigue Syndrome.

BACKGROUND: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating condition that can lead to severe impairment of physical, psychological, cognitive, social, and occupational functions. The cause of ME/CFS remains incompletely understood. There is no clinical diagnostic test for ME/CFS. Although many therapies have been used off-label to manage symptoms of ME/CFS, there are limited, if any, specific therapies or cure for ME/CFS. In this study, we investigated the expression of genes specific to key immune functions, and viral infection status in ME/CFS patients with an aim of identifying biomarkers for characterization and/or treatment of the disease. METHODS: In 2021, one-hundred and sixty-six (166) patients diagnosed with ME/CFS and 83 healthy controls in the US participated in this study via a social media-based application (app). The patients and heathy volunteers consented to the study and provided self-collected finger-stick blood and first morning void urine samples from home. RNA from the fingerstick blood was tested using DxTerity's 51-gene autoimmune RNA expression panel (AIP). In addition, DNA from the same fingerstick blood sample was extracted to detect viral load of 4 known ME/CFS associated viruses (HHV6, HHV7, CMV and EBV) using a real-time PCR method. RESULTS: Among the 166 ME/CFS participants in the study, approximately half (49%) of the ME/CFS patients reported being house-bound or bedridden due to severe symptoms of the disease. From the AIP testing, ME/CFS patients with severe, bedridden conditions displayed significant increases in gene expression of IKZF2, IKZF3, HSPA8, BACH2, ABCE1 and CD3D, as compared to patients with mild to moderate disease conditions. These six aforementioned genes were further upregulated in the 22 bedridden participants who suffer not only from ME/CFS but also from other autoimmune diseases. These genes are involved in T cell, B cell and autoimmunity functions. Furthermore, IKZF3 (Aiolos) and IKZF2 (Helios), and BACH2 have been implicated in other autoimmune diseases such as systemic lupus erythematosus (SLE) and Rheumatoid Arthritis (RA). Among the 240 participants tested with the viral assays, 9 samples showed positive results (including 1 EBV positive and 8 HHV6 positives). CONCLUSIONS: Our study indicates that gene expression biomarkers may be used in identifying or differentiating subsets of ME/CFS patients having different levels of disease severity. These gene targets may also represent opportunities for new therapeutic modalities for the treatment of ME/CFS. The use of social media engaged patient recruitment and at-home sample collection represents a novel approach for conducting clinical research which saves cost, time and eliminates travel for office visits.

Sarcopenic Obesity in Cervical Carcinoma: A Strong and Independent Prognostic Factor beyond the Conventional Predictors (ESTHER Study-AFRAID Project).

Locally advanced cervical cancer represents a significant treatment challenge. Body composition parameters such as body mass index, sarcopenia, and sarcopenic obesity, defined by sarcopenia and BMI ≥ 30 kg/m2, have been identified as potential prognostic factors, yet their overall impact remains underexplored. This study assessed the relationship between these anthropometric parameters alongside clinical prognostic factors on the prognosis of 173 cervical cancer patients. Survival outcomes in terms of local control (LC), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) were analyzed using Kaplan regression methods-Meier and Cox. Older age, lower hemoglobin levels, higher FIGO (International Federation of Gynecology and Obstetrics) stages, and lower total radiation doses were significantly associated with worse outcomes. Univariate analysis showed a significant correlation between BMI and the outcomes examined, revealing that normal-weight patients show higher survival rates, which was not confirmed by the multivariate analysis. Sarcopenia was not correlated with any of the outcomes considered, while sarcopenic obesity was identified as an independent negative predictor of DFS (HR: 5.289, 95% CI: 1.298-21.546, p = 0.020) and OS (HR: 2.645, 95% CI: 1.275-5.488, p = 0.009). This study highlights the potential of sarcopenic obesity as an independent predictor of clinical outcomes. These results support their inclusion in prognostic assessments and treatment planning for patients with advanced cervical cancer.

Degos' syndrome complicated by bowel perforation: focus on radiological findings.

We describe a 50-year-old man who first presented with multiple skin lesions which were characteristic of Degos' syndrome. The patient developed multiple episodes of abdominal pain. Some episodes resolved with conservative management, for others he underwent urgent operations for bowel perforations. The patient subsequently underwent extensive small bowel resection, but further systemic deterioration ensued and he died. The imaging findings of Degos' syndrome and the implications of pneumatosis intestinalis and pneumoperitoneum are discussed.

Fatal cerebral air embolism related to an air flight.

A patient with chronic obstructive pulmonary disease developed a cough, loss of consciousness, and convulsions during an air flight. Chest radiography showed a large lung bulla. Computed tomography of the brain showed intraparenchymal air and bilateral cerebral infarcts. The findings were compatible with cerebral air embolism, most likely predisposed to by lung bulla and an air flight. The underlying pathology and possible treatment are discussed.

Decoding the Complexity of Systemic Inflammation Predictors in Locally Advanced Cervical Cancer, with Hemoglobin as the Hidden Key (the ESTHER Study).

Locally advanced cervical cancer (LACC) is treated with concurrent chemoradiation (CRT). Predictive models could improve the outcome through treatment personalization. Several factors influence prognosis in LACC, but the role of systemic inflammation indices (IIs) is unclear. This study aims to assess the correlation between IIs and prognosis in a large patient cohort considering several clinical data. We retrospectively analyzed pretreatment IIs (NLR, PLR, MLR, SII, LLR, COP-NLR, APRI, ALRI, SIRI, and ANRI) in 173 LACC patients. Patient, tumor, and treatment characteristics were also considered. Univariate and multivariate Cox's regressions were conducted to assess associations between IIs and clinical factors with local control (LC), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS). Univariate analysis showed significant correlations between age, HB levels, tumor stage, FIGO stage, and CRT dose with survival outcomes. Specific pretreatment IIs (NLR, PLR, APRI, ANRI, and COP-NLR) demonstrated associations only with LC. The multivariate analysis confirmed Hb levels, CRT dose, and age as significant predictors of OS, while no II was correlated with any clinical outcome. The study findings contradict some prior research on IIs in LACC, emphasizing the need for comprehensive assessments of potential confounding variables.

Classical Prognostic Factors Predict Prognosis Better than Inflammatory Indices in Locally Advanced Cervical Cancer: Results of a Comprehensive Observational Study including Tumor-, Patient-, and Treatment-Related Data (ESTHER Study).

Systemic inflammation indices were found to be correlated with therapeutic outcome in several cancers. This study retrospectively analyzes the predictive role of a broad range of systemic inflammatory markers in patients with locally advanced cervical cancer (LACC) including patient-, tumor-, and treatment-related potential prognostic factors. All patients underwent definitive chemoradiation and pretreatment values of several inflammatory indices (neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio, monocyte/lymphocyte ratio, systemic immune inflammation index (SII), leukocyte/lymphocyte ratio, combination of platelet count and NLR, aspartate aminotransferase/platelet ratio index, aspartate aminotransferase/lymphocyte ratio index, systemic inflammatory response index, and aspartate transaminase/neutrophil ratio index) were calculated. Their correlation with local control (LC), distant metastasis-free (DMFS), disease-free (DFS), and overall survival (OS) was analyzed. One hundred and seventy-three patients were included. At multivariable analysis significant correlations were recorded among clinical outcomes and older age, advanced FIGO stage, lower hemoglobin levels, larger tumor size, and higher body mass index values. The multivariate analysis showed only the significant correlation between higher SII values and lower DMFS rates (p < 0.01). Our analysis showed no significant correlation between indices and DSF or OS. Further studies are needed to clarify the role of inflammation indices as candidates for inclusion in predictive models in this clinical setting.

Comparative Effectiveness of Chemotherapy Alone Versus Radiotherapy-Based Regimens in Locally Advanced Pancreatic Cancer: A Real-World Multicenter Analysis (PAULA-1).

Different options for locally advanced pancreatic cancer (LAPC) are available based on international guidelines: chemotherapy (CHT), chemoradiation (CRT), and stereotactic body radiotherapy (SBRT). However, the role of radiotherapy is debated in LAPC. We retrospectively compared CHT, CRT, and SBRT ± CHT in a real-world setting in terms of overall survival (OS), local control (LC), and distant metastasis-free survival (DMFS). LAPC patients from a multicentric retrospective database were included (2005-2018). Survival curves were calculated using the Kaplan-Meier method. Multivariable Cox analysis was performed to identify predictors of LC, OS, and DMFS. Of the 419 patients included, 71.1% were treated with CRT, 15.5% with CHT, and 13.4% with SBRT. Multivariable analysis showed higher LC rates for CRT (HR: 0.56, 95%CI 0.34-0.92, p = 0.022) or SBRT (HR: 0.27, 95%CI 0.13-0.54, p < 0.001), compared to CHT. CRT (HR: 0.44, 95%CI 0.28-0.70, p < 0.001) and SBRT (HR: 0.40, 95%CI 0.22-0.74, p = 0.003) were predictors of prolonged OS with respect to CHT. No significant differences were recorded in terms of DMFS. In selected patients, the addition of radiotherapy to CHT is still an option to be considered. In patients referred for radiotherapy, CRT can be replaced by SBRT considering its duration, higher LC rate, and OS rate, which are at least comparable to that of CRT.

Acute ischaemic stroke during short-term travel to high altitude.

This is a case report of a young healthy adult who had acute cerebral infarcts after a short-term visit to high-altitude area. He developed acute onset of right-sided limb weakness and right hemianopia a few hours after arrival at an altitude of 3600 m by train. He was initially treated for high-altitude cerebral oedema but later computed tomography and magnetic resonance imaging confirmed ischaemic infarcts in the medial left occipital lobe and left thalamus. Subsequent investigations, including laboratory tests and imaging including an echocardiogram, revealed no culpable predisposing factors.

Different facets of intracranial central nervous system lymphoma and its imaging mimics.

Lymphomas of the central nervous system (CNS) are broadly classified into primary CNS lymphoma (PCNSL) and secondary CNS lymphoma (SCNSL). PCNSL refers to lymphoma restricted to the brain, leptomeninges, spinal cord, or eyes without evidence of it outside the CNS at primary diagnosis, while SCNSL refers to secondary CNS involvement by systemic lymphoma. The brain is the most common site of involvement and intracranial CNS lymphoma has a highly variable imaging appearance and varies according to the patient's clinical profile and immunity. This pictorial essay aims to illustrate the different facets of intracranial CNS lymphomas on neuroimaging. This enables radiologists to be familiarized with their key diagnostic features and differentiate from their differential diagnoses, leading to early diagnosis, and treatment.

Paget-Schroetter syndrome in a non athlete - a case report.

A young male waiter presented with left shoulder pain, with ultrasound showing thrombosis of the left subclavian vein. After exclusion of hypercoagulability, a dynamic MRI upper limb venogram was performed, confirming Paget-Schroetter syndrome (PSS). Our case is unusual as Paget Schroetter syndrome are seldom reported in non athletes. This is also the first report to show dynamic MRI images of PSS.

Gallium-67 Scan with Single Photon Emission Computed Tomography for the Evaluation and Monitoring of Infected Abdominal Aortic Aneurysms: A 10-Year Case Series.

PURPOSE: This study aimed to evaluate the role of gallium-67 single photon emission computed tomography (SPECT) with contrast computed tomography (CT) in the evaluation and monitoring of infected abdominal aortic aneurysms (IAAA). MATERIALS AND METHODS: A retrospective cohort analysis was performed using prospectively collected data of consecutive patients with IAAA in Princess Margaret Hospital in Hong Kong between January 2010 and December 2020. The patients were identified using the Radiology Information System. RESULTS: All five patients had proven IAAA on CT and/or metabolic imaging. Among them, three were further supported by positive blood culture results. Gallium- 67 SPECT with contrast CT was useful in the detection of residual disease, monitoring, and detection of recurrence. CONCLUSION: Gallium-67 SPECT with contrast CT is helpful for evaluating IAAA. It serves an important role in guiding management, especially during long-term follow-up.

US findings of melamine-related renal disorders in Hong Kong children.

BACKGROUND: The melamine-tainted milk incident has caused renal disorders in more than 290,000 children from mainland China since the start of the outbreak in 2008. Since then, more than 27,000 children in Hong Kong have undergone renal US screening. OBJECTIVE: To present and discuss the US features of melamine-related renal abnormalities in Hong Kong children. MATERIALS AND METHODS: Between September 2008 and February 2009, 3,835 children attended the Department of Radiology of Princess Margaret Hospital for renal US examination. CT or plain abdominal radiography was performed in those with inconclusive findings. The US findings of detected melamine-related renal disorders were analysed. RESULTS: Echogenic foci in the kidneys were found in 22 children (0.6%). These were located in the renal pelvicalyceal system (in 12 children) and in the renal medulla (in 10 children). The echogenic foci measured 0.1-0.7 cm, with 6 children showing posterior acoustic shadowing, 14 showing comet-tail artefacts, and 2 showing echogenic dots. CONCLUSION: The incidence of renal disorders amongst Hong Kong children exposed to melamine was lower than in their mainland China counterparts. The renal stones detected were also relatively small, with most demonstrating comet-tail artefacts instead of posterior acoustic shadowing.

Hybrid method in severe pulmonary embolism not suitable for systemic fibrinolysis.

Acute massive pulmonary embolism is known to be associated with high mortality, and treatment options may be limited if systemic fibrinolysis is contraindicated. We report the exciting results of a novel mechanical-pharmacological hybrid approach in 3 patients with life-threatening massive pulmonary embolism, in whom systemic fibrinolysis was contraindicated.

Effect of a therapeutic maximum allowable cost (MAC) program on the cost and utilization of proton pump inhibitors in an employer-sponsored drug plan in Canada.

BACKGROUND: Therapeutic maximum allowable cost (MAC) is a managed care intervention that uses reference pricing in a therapeutic class or category of drugs or an indication (e.g., heartburn). Therapeutic MAC has not been studied in Canada or the United States. The proton pump inhibitor (PPI) rabeprazole was used as the reference drug in this therapeutic MAC program based on prices for PPIs in the province of Ontario. No PPI is available over the counter in Canada. OBJECTIVE: To evaluate the utilization and anticipated drug cost savings for PPIs in an employer-sponsored drug plan in Canada that implemented a therapeutic MAC program for PPIs. METHODS: An employer group with an average of 6,300 covered members, which adopted the MAC program for PPIs in June 2003, was compared with a comparison group comprising the book of business throughout Canada (approximately 5 million lives) without a PPI MAC program (non-MAC group). Pharmacy claims for PPIs were identified using the first 6 characters of the generic product identifier (GPI 492700) for a 36-month period from June 1, 2002, through May 31, 2005. The primary comparison was the year prior to the intervention (from June 1, 2002, through May 31, 2003) and the first full year following the intervention (June 1, 2004, through May 31, 2005). Drug utilization was evaluated by comparing the market share of each of the PPIs for the 2 time periods and by the days of PPI therapy per patient per year (PPPY) and days of therapy per prescription (Rx). Drug cost was defined as the cost of the drug (ingredient cost), including allowable provincial pharmacy markup but excluding pharmacy dispense fee. Cost savings were calculated from the allowed drug cost per claim, allowed cost per day, and allowed cost PPPY. RESULTS: (All amounts are in Canadian dollars.) The MAC intervention group experienced an 11.7% reduction in the average cost per day of PPI drug therapy, from 2.14 US dollars in the preperiod to 1.89 US dollars in the postperiod, compared with a 3.7% reduction in the comparison group (2.16 US dollars vs. 2.08 US dollars). Utilization dropped by 11.9% in the intervention group, from 166.7 days of PPI drug therapy PPPY to 146.9 days PPPY, compared with an increase of 7.9% in the comparison group, from 136.1 days to 146.8 days PPPY. The combined effect of the decrease in drug cost per day and utilization was a 22.1% reduction in allowed drug cost PPPY in the intervention (MAC) group (from 357 US dollars to 278 US dollars PPPY) versus a 4.1% increase in the comparison group (from 293 US dollars to 305 US dollars PPPY). CONCLUSION: A MAC program for PPIs for one employer in Canada was associated with savings for the drug plan sponsor of approximately 8% in actual drug cost per day of therapy compared with the comparison group. Total savings after consideration of utilization was approximately 26% for the intervention group versus the comparison group.

Early Enlargement of Aneurysmal Sac and Separation of EndoBags of Nellix Endovascular Aneurysm Sealing System as Signs of Increased Risk of Later Aneurysm Rupture.

Nellix Endovascular Aneurysm Sealing (EVAS) system is a new concept and technology of abdominal aortic aneurysm (AAA) repair. Elective EVAS using Nellix device was performed for a 83-year-old man with AAA. 2-month post-EVAS CTA surveillance demonstrated mild enlargement of aneurysmal sac and separation of the EndoBags, but without detectable endoleak. The patient developed sudden AAA rupture with retroperitoneal hematoma at about 4 months after EVAS. We postulated that early enlargement of aneurysmal sac and separation of EndoBags of Nellix devices after EVAS, even without detectable endoleak, might indicate significant aneurysmal wall weakening with increased risk of later AAA rupture. To the best of the authors' knowledge, this was the first reported case of aortic rupture after EVAS without detectable endoleak during and after the procedure.

Medications as causes of intraluminal hyperdensities: what radiologists need to know.

In computed tomography (CT) angiogram or some dedicated CT studies of the abdomen, the use of positive enteric contrast should be avoided as its presence could decrease the sensitivity of the test. There are, however, cases of CT scans with unexpected hyperdense intraluminal contents detected due to the use of certain oral or rectal medications. Reports on medications as causes of intraluminal hyperdensities are sparse in the English literature. We have studied several commonly used medications and revealed that many drugs appear hyperdense in CT scans. The presence of unexpected intraluminal hyperdensities can potentially cause erroneous interpretation of images and in some cases decrease the sensitivity of the test. The hyperdense bowel contents may be mistaken as acute hemorrhage in CT angiogram for detection of GI bleeding. Active GI bleeding, presented as intraluminal extravasation of contrast material, can also be obscured. Certain intra-abdominal pathologies could be masked, for example, in plain CT scan for detection of urinary tract stones or in contrast CT study for suspected bowel ischaemia. It is important for radiologists and clinicians to be aware of this situation in order to prevent misinterpretation of images and to select the most appropriate imaging modality when such unexpected intraluminal hyperdensities are encountered.

Heart failure: is there a role for angiotensin II receptor blockers?

Angiotensin II receptor blockers (ARBs) directly inhibit the angiotensin II type 1 receptors, which suppresses the renin-angiotensin-aldosterone system (RAAS). Six ARBs are approved in Canada for the treatment of hypertension, none are yet approved for the treatment of heart failure (HF). Evidence comparing ARBs to angiotensin converting enzyme inhibitors (ACEIs) in HF is still limited. A recent meta-analysis of 17 clinical trials could not confirm that ARBs are superior to ACEIs in reducing either mortality or hospitalization in HF patients. ARBs may be used as an alternative in HF patients intolerant of ACEIs. A meta-analysis indicates that, compared to using an ACEI alone, adding an ARB to an ACEI carries the potential for additional benefits in terms of reduced hospitalization, but not mortality. However, the FDA determined there is currently insufficient evidence of such additional benefit when valsartan is combined to an ACEI in patients with HF.