Reduced doses of emicizumab achieve good efficacy: Results from a national-wide multicentre real-world study in China.

INTRODUCTION: Reduced doses of emicizumab improve the affordability among patients in developing countries. However, the relationship between variant dose selection and efficacy in the real world of China is still unclear. AIM: This study aimed to investigate the efficacy and safety of emicizumab especially in those on reduced dose regimens in a real-world setting. METHODS: We carried out a multicentre study from 28 hospitals between June 2019 and June 2023 in China and retrospectively analysed the characteristics including demographics, diagnosis, treatment, bleeding episodes, and surgical procedures. RESULTS: In total, 127 patients with haemophilia A, including 42 with inhibitors, were followed for a median duration of 16.0 (IQR: 9.0-30.0) months. Median age at emicizumab initiation was 2.0 (IQR: 1.0-4.0) years. Median (IQR) consumption for loading and maintenance was 12.0 (8.0-12.0) and 4.2 (3.0-6.0) mg/kg/4 weeks, respectively. While on emicizumab, 67 (52.8%) patients had no bleeds, whereas 60 (47.2%) patients had any bleeds, including 26 with treated bleeds. Compared to previous treatments, patients on emicizumab had significantly decreased annualized bleeding rate, annualized joint bleeding rate, target joints and intracerebral haemorrhage. Different dosages had similar efficacy except the proportion of patients with treated spontaneous bleeds and target joints. Adverse events were reported in 12 (9.4%) patients. Postoperative excessive bleeding occurred following two of nine procedures. CONCLUSION: This is the largest study describing patients with HA receiving emicizumab prophylaxis on variant dose regimens in China. We confirmed that nonstandard dose is efficacious and can be considered where full-dose emicizumab is ill affordable.

Synchronous Double Primary Tumors of Liver (Small Cell Neuroendocrine Carcinoma and Hepatocellular carcinoma): A Case Report.

This study presents a case of dual primary liver cancer involving small cell neuroendocrine carcinoma and hepatocellular carcinoma. The 58-year-old Chinese male patient, who has a medical history of viral hepatitis B, presented with right upper abdominal pain persisting for one month. Imaging studies indicated the presence of multiple liver masses in segments V and VII-VIII, as well as a mass in the left lung. Subsequent hepatic biopsy performed on both segments confirmed the presence of hepatocellular carcinoma in segment V and small cell neuroendocrine carcinoma in segment VII-VIII. After undergoing one cycle of chemotherapy, the lung mass exhibited a reduction in size, while the liver masses showed an inadequate response. Subsequently, the patient underwent Transcatheter Arterial Chemoembolization (TACE) and Hepatic Artery Infusion Chemotherapy (HIAC), resulting in partial remission (PR). However, the patient was diagnosed with brain metastasis and subsequently treated with Sorafenib and Tirelizumab, a Programmed Death 1 (PD-1) immune checkpoint inhibitor. The efficacy evaluation indicated stability, and no severe adverse effects were observed at the time of writing. The patient's survival time was 16 months.

Inflammatory cutaneous metastases originating from gastric cancer: A case report.

BACKGROUND: Cutaneous metastasis with gastric cancer (GC) origin is extremely rare and associated with poor prognosis. Nodular type is the most common type, while other forms are extremely rare. CASE SUMMARY: This study describes severe skin redness, swelling, pain, and fever in a 65-year-old man diagnosed with GC, whose left chest wall, left upper limb, and left back were mainly affected. Firstly, the patient was diagnosed with "lymphangitis" and treated to promote lymphatic return. However, the symptoms were constantly deteriorating, and skin thickening and scattered small nodules gradually appeared. Finally, the skin biopsy confirmed cutaneous metastases, and the patient died 7 d later. CONCLUSION: Our case highlights that cutaneous metastasis should be considered when skin lesions appear in patients with GC.

Case report: A case of incontinentia pigmenti.

Incontinentia pigmenti (IP) is a rare neuroectodermal dysplasia caused by mutations in the IKBKG gene. We present a case of a 4-month-old female infant with erythematous vesicular skin lesions on the trunk and extremities. Histopathologic examination of the blisters revealed an eosinophilic infiltrate. Further investigation revealed that her mother had three unexplained miscarriages and two normal uncomplicated pregnancies, resulting in the birth of two male infants. We performed a comprehensive genetic evaluation to rule out the interference of pseudogene IKBKGP, and the infant was finally diagnosed with IP. During the subsequent 2-year follow-up, we observed a significant improvement in her dermatologic symptoms, with no evidence of recurrence, and there were no other associated symptoms in the hair, nails, oral mucosa, eyes, or central nervous system.

Epithelioid hemangioendothelioma of the retroperitoneal giant type treated with Toripalimab: A case report.

Epithelioid hemangioendotheliomas (EHEs), low-grade malignant tumors of vascular endothelial cell origin, are characterized by vascular endothelial proliferation. In 2002, the World Health Organization classified EHEs as locally aggressive tumors with the potential to metastasize. Currently, the diagnosis of EHE is based on pathology, histological and immunohistochemical examinations. There are no standard treatment guidelines. We here report a 69-year-old man who presented with left-sided chest and abdominal pain for more than 2 months. Enhanced computed tomography of the thorax and abdomen in another hospital suggested a mass in the left adrenal region that was considered malignant. Positron emission tomography- computed tomography in our hospital suggested a large multi-loculated, hypermetabolic, cystic mass in the left adrenal region that was considered malignant. Accordingly, a puncture biopsy of the mass was performed and the diagnosis of EHE confirmed by pathological examination, including immunohistochemical staining. This patient was treated with the programmed death 1 (PD-1) immune checkpoint inhibitor toripalimab with long-term success. The best response was stable disease (SD) with a progression-free survival (PFS) of more than 13 months. The patient is still alive now. Because the sample size of previous studies was small, further studies are needed to determine the safety and efficacy of toripalimab in the treatment of EHE.

Variant spectrum of F8 and F9 in hemophilia patients from southern China and 26 novel variants.

Hemophilia, an X-linked recessive disorder, is characterized by spontaneous or trauma-induced prolonged bleeding. It is classified as hemophilia A when caused by variants in the F8 gene, and hemophilia B when caused by F9 variants. Few studies have described hemophilia variants in the Chinese population. This study aimed to investigate the clinical and genetic profiles of 193 hemophilia patients from southern China. Utilizing Sanger sequencing, multiplex ligation-dependent probe amplification, gap detection, long-range PCR, and multiplex PCR, we identified both F8 and F9 gene variants. Pregnant women with a history of hemophilia A offspring underwent amniocentesis or villus sampling for the variant detection. Variants in F8 and F9 were pinpointed in 183 patients, with 26 being novel discoveries. Notably, genetic testing was absent in the initial evaluation of 133 out of 161 patients, leading to a protracted average definitive diagnosis timeline of 2 years. Remarkably, two hemophilia A cases with anticipated severe phenotypes due to protein-truncating variants presented with only moderate or mild clinical manifestations. Among the 40 fetuses tested, 34 were males, with 17 exhibiting hemizygous variants in the F8 gene. Our results contribute to the broader understanding of F8 and F9 variant spectrum and highlight the underuse of genetic analyses in southern China.

Cardiac metastasis from small cell lung cancer origin: A case report and review of the literature.

BACKGROUND: Cardiac metastasis from small cell lung cancer (SCLC) origin is rare, whereas the incidence is anticipated to increase with the extended survival rates. CASE: We here describe a case report of a 48-year-old male patient diagnosis with SCLC in 2020. In June 2021, he resorted to hospital due to shortness of breath, no obvious changes were found in repeated echocardiography, electrocardiogram and chest computer tomography from June 2021 to September 2021. Due to the persistence of the complaints, cardiac magnetic resonance (CMR) imaging was performed in September 30th, 2021, which showed a mass in the right atrioventricular groove. The patient underwent pericardiocentesis and small cell carcinoma cells were found in the pericardial effusion, confirming the diagnosis of cardiac metastasis. CONCLUSION: Patients with a history of SCLC who develop new cardiac symptoms of unknown etiology should undergo imaging studies such as CMR. The importance of CMR for patients with SCLC is highlighted. The literature regarding metastatic cardiac tumors is reviewed.

ELISA based assays to measure adenosine deaminases concentration in serum and saliva for the diagnosis of ADA2 deficiency and cancer.

Adenosine deaminases (ADAs) are enzymes of purine metabolism converting adenosine to inosine. There are two types of ADAs in humans ADA1 and ADA2. While both ADA1 and ADA2 share the same substrate, they differ in expression, cellular localization, and catalytic properties. The genetic deficiency of ADA1 results in severe combined immunodeficiency (SCID), while lack in ADA2 (DADA2) results in multiple phenotypes ranging from systemic inflammation to vascular pathology. Clinical studies have shown that the levels of ADAs in biological fluids are altered in pathophysiological conditions, suggesting that ADA activity could be a convenient marker for the diagnosis of immune diseases and cancer. Here, we describe sensitive and straightforward ELISA assays to measure ADA1 and ADA2 concentrations in biological fluids. Analysis of the serum and saliva samples from the healthy controls and DADA2 patients revealed that ADA2 enzyme concentration is significantly lower in patients than in healthy controls. In contrast, the concentration of ADA2 increases in the serum of patients with large granular leukocyte leukemia (LGLL) and patients' saliva with head and neck cancer. Thus, this simple, non-invasive method allows for distinguishing healthy controls from the affected patient. It can be implemented in screening and diagnosis of DADA2 and follow up the treatment of LGLL and several types of head and neck cancer.

Uncovering of potential molecular markers for cervical squamous cell carcinoma (CESC) based on analysis of methylated-differentially expressed genes.

OBJECTIVE: Cervical squamous cell carcinoma (CESC) is a cancer with high mortality caused by human papillomavirus. The aim of this study was to uncover potential CESC biomarkers to help early diagnosis and treatment. MATERIALS AND METHODS: The mRNA transcriptome data and DNA methylation data were downloaded from database for the identification of differentially expressed mRNAs (DEmRNAs) and DNA methylation analysis. Functional analysis was used to reveal the molecular functions. Then, the association between differential methylation and DEmRNA was analyzed. Protein-protein interaction (PPI) network analysis was performed on the selected differentially methylated genes (DEGs). Subsequently, we analyzed the prognosis and constructed a prognostic risk model. We also performed diagnostic analyses of risk model genes. In addition, we verified the protein expression level of identified DEGs. RESULTS: 1438 DEmRNAs, 1669 differentially methylated sites (DMSs), 46 differentially methylated CpG islands and 53 differential methylation genes (DMGs) were obtained. In PPI, the highest interaction scores were MX2 and IRF8, and their interaction score was 0.928. Interestingly, 5 DMGs were found to be associated with CESC prognosis. In addition, our results demonstrated that high risk score was associated with poor prognosis of CESC. Furthermore, it was found that ZIK1, ZNRF2, HHEX, VCAM1 could be diagnostic molecular markers for CESC. CONCLUSION: Analysis of methylated-differentially expressed genes may contribute to the identification of early diagnosis and therapeutic targets of CESC. In addition, a prognostic model based on 5 DMGs can be used to predict the prognosis of CESC.