Concomitant Presence of Hb Agrinio and - -Med Deletion in a Greek Male Patient with Hemoglobinopathy H: More Severe Phenotype and Literature Review.

Hemoglobin (Hb) Agrinio is a rare non-deletional a-globin mutation observed almost exclusively in Greek, Spanish or other Mediterranean families. The clinical manifestations of a carrier of a single Hb Agrinio mutation (single heterozygosity) depend on the concomitant presence or absence of other mutations or variants in the beta, alpha or other modifying genes. We present a Greek patient harboring a Hb Agrinio variant plus the - -Med alpha deletional allele, having an infrequent severe form of alpha thalassemia, in contrast to the typical alpha thalassemic patient and requiring regular red blood cell (RBC) transfusions and chelation treatment. We also provide a concise literature review regarding alpha thalassemic hemoglobin variants and their molecular and clinical combinations. A phase 2, double-blind, randomized, placebo-controlled, multicenter clinical trial to determine the efficacy and safety of luspatercept (BMS-986346/ACE-536) for the treatment of anemia in adults with alpha thalassemia with the participation of our center is currently recruiting patients (NCT05664737).

Clinical significance of mutational variants in beta and alpha genes in patients with hemoglobinopathies from two large Greek centers: a complex interplay between genotype and phenotype.

Hemoglobinopathies affect patients in the wider Mediterranean area consisting of 4 distinct subgroups: beta thalassemia major (TM), beta thalassemia intermedia (TI), sickle cell disease (SCD) and hemoglobin H disease (alpha thalassemia). The clinical spectrum varies from mild to severe. Complex interactions between genes and environmental factors form the clinical manifestations. There is an unmet need to clarify these multifactorial mechanisms. This is the first Greek study describing mutational alleles (HBB and HBA1/HBA2 gene variants) in 217 patients with hemoglobinopathies of two large centers in Greece (Larissa and Athens) and associating particular genotypes or gene variants with clinical manifestations (transfusion frequency, complications). Thus, the complex interplay between corresponding genotypes and phenotypes was investigated. Our results are in accordance with previous national studies with limited variations, due to regional prevalence of specific gene variants, as expected. It is also a description of the prevalence of hemoglobinopathies in the Greek population. The type and prevalence of beta and alpha globin gene variants differ significantly among countries. We also confirm the well-known observation of many studies that in our beta thalassemic or SCD patients, co-inheritance of variants in the alpha globin genes, leading to absence or reduction of alpha globin synthesis were associated with milder clinical course, whereas the inheritance of additional alpha genes (triplication) led to a more severe clinical phenotype. In cases in whom the genotype and phenotype did not correlate, factors like the function or modification of possible regulatory genes or additional nutritional-environmental effects should be investigated. KEY MESSAGES: • This is the first Greek study, fully molecularly defining the beta and alpha mutational alleles in 217 patients with hemoglobinopathies of two large centers in Greece and correlating particular genotypes or gene variants with clinical manifestations (transfusion frequency, complications). • In the beta thalassemic or SCD patients of our cohort, co-inheritance of variants in the alpha globin genes, leading to absence or reduction of alpha globin synthesis were associated with milder clinical course (confirmation of a well-known previous observation). • The inheritance of additional alpha genes (triplication) led to a more severe clinical phenotype (confirmation of a well known previous observation). • The function or modification of possible regulatory genes should be investigated in cases in whom the genotype and phenotype did not correlate.

Inadvertent direct pulmonary artery catheterization complicating the effort for subclavian venous cannulation and central venous catheter placement: A case report and review of the literature.

Subclavian access is commonly used in the intensive care unit (ICU) for central venous catheterization. Many complications have been reported during the placement of central venous catheters including pneumothorax, hemothorax, hematoma, and bleeding. The direct, through the thoracic wall, catheterization of pulmonary artery is a very rare one with only three previous reports in the literature. We report a patient who was catheterized for subclavian venous catheter placement, but the imaging techniques (chest X-ray and computed tomography with reconstruction of the images) revealed the direct positioning of the catheter into the pulmonary trunk, fortunately without other adverse events for the patient. Our case report in accordance with recent review of the literature strongly emphasizes the benefits of performing ultrasound-guided interventions in ICU.

Open Repair of a Ruptured Abdominal Aortic Aneurysm on a Patient Under Rivaroxaban and Clopidogrel.

BACKGROUND: Direct oral anticoagulants are commonly used instead of vitamin K antagonists in patients needing long-term anticoagulant treatment. As their use has become more popular, there is an increase possibility to perform a major surgery on an urgent or emergency basis on patients under nonvitamin-K antagonist oral anticoagulants. CASE REPORT: We report a case of a ruptured abdominal aortic aneurysm on a male patient under rivaroxaban and clopidogrel. Emergency open repair of the aneurysm was performed. No anti-Xa antidote was administered. The patient had an uneventful recovery. CONCLUSION: An open repair of a ruptured abdominal aortic aneurysm under rivaroxaban is feasible. However, an antidote should be available in cases of uncontrolled diffused bleeding. To the best of our knowledge, this is the first reported case of successful open repair of a ruptured abdominal aortic aneurysm on a patient under rivaroxaban and clopidogrel.

Hepatorenal Revascularization Enables Endovascular Aneurysm Repair on a Patient with Abdominal Aortic Aneurysm and an Ectopic Right Renal Artery.

In last 30 years, the endovascular aneurysm repair (EVAR) has become the standard method of treatment of abdominal aortic aneurysms (AAAs). Nevertheless, the method has limitations mainly based on the anatomic characteristics of the specific aneurysm. In these cases, a combination of endovascular and open techniques can be used. We describe a case of a patient with an infrarenal AAA and an ectopic right renal artery emerging from within the aneurysm sac. The patient was treated with a combination of endovascular and open techniques. In particular, he underwent a hepatorenal revascularization followed by a standard EVAR procedure, with a successful final outcome. For the treatment of AAA disease, the combination of open and endovascular procedures can overcome difficulties, where a standard EVAR cannot be an option.

Metastasectomy of pancreatic and periampullary adenocarcinoma to solid organ: The current evidence.

PURPOSE: Pancreatic and periampullary adenocarcinoma have not generally been included in the tumour types considered for metastasectomy. However, there is an increasing interest that metastasectomy in well-selected patients can prolong survival. This review aims to establish the recent evidence on the surgical management of oligometastatic disease and survival outcome in patients who underwent metastasectomy focusing on isolated hepatic and pulmonary metastases. METHODS: A systematic search was performed in the PubMed database to identify all original articles on the role of metastasectomy for oligometastasis of pancreatic and periampullary adenocarcinoma. Data on methodologies used, 1,3,5 - year survival and median overall survival were summarized, and used to address relevant clinical questions related to the survival outcome in patients who underwent metastasectomy. RESULTS: Sixteen studies were included in this review. All the studies included were retrospective and heterogenous in nature and did not have a uniform reporting on survival outcomes. CONCLUSION: There is insufficient evidence to support a change of current practice in managing metastatic pancreatic and periampullary cancer. However, patients with ampullary cancer as the primary and any patients with first recurrence as isolated pulmonary metastases had better prognosis than patients with synchronous metastasis or metastases to the liver. This need to be explored in future studies.

Body Composition in Adult Patients with Thalassemia Major.

Objective. To assess body composition in adult male and female patients with thalassemia major by dual-energy X-ray absorptiometry (DXA) and to compare the findings with a group of healthy age-matched controls. Methods. Our study group included sixty-two patients (27 males, mean age 36 years, and 35 females, mean age 36.4 years) and fifteen age-matched healthy controls. All patients had an established diagnosis of thalassemia major and followed a regular blood transfusion scheme since childhood and chelation treatment. Fat, lean, and bone mineral density (BMD) were assessed with dual-energy X-ray absorptiometry. Ferritin levels and body mass index of all patients and controls were also recorded. Student t-test and Wilcoxon test were performed and statistical significance was set at p < 0.05. Results. BMD and whole body lean mass are lower in both male and female adult patients compared with controls (p < 0.01 in both groups), whereas whole body fat mass was found to have no statistically significant difference compared to controls. Regional trunk fat around the abdomen was found to be lower in male patients compared to controls (p = 0.02). Conclusion. Severe bone loss and diminished lean mass are expected in adult male and female patients with thalassemia major. Fat changes seem to affect mainly male patients.

Multifocal septic osteomyelitis mimicking skeletal metastatic disease in a patient with prostate cancer.

We present an unusual case of a 59 years old patient with prostate cancer, who was referred to our hospital with pleurodenia, low back and other sites of bone ostalgia, for bone scintiscan. The patient underwent a whole body bone scanning after the intravenous administration of 740MBq (99m)Tc-methylene diphosphonate (MDP). The main findings of the study were: increased radiotracer uptake at the T5, T9-T10 vertebrae, the head of the 11th rib and the area of the left sternoclavicular joint (SCJ), which were initially attributed to skeletal metastatic lesions. Another "hot" area in the left knee, was consistent with severe arthritis. Physical examination revealed fever up to 38.7°C, tenderness and swelling of his left knee and various painful sites. Due to persistent fever and markedly raised inflammatory markers (ESR 102mm/h, CRP 73.8mg/L, WBC 16.800 cells/µ L - neutrophils 78%, lymphocytes 15%, monocytes 5%, eosinophils 1%), the patient was further referred for a magnetic resonance (MR) scan with specific interest on the thoracic spine and the SCJ. In the sagittal short-tau inversion recovery (STIR) MR image, abnormally high signal involving both T9 and T10 vertebral bodies due to bone marrow oedema and irregularity of the endplates with focal destruction areas, were observed. The T9-T10 intervertebral disc had an abnormally high signal suggestive of "hot disc" sign and also a prevertebral soft tissue mass abutting the anterior aspect of the involved vertebral bodies. The axial T1-weighted image with fat saturation post gadolinium (Gd), revealed diffuse strong enhancement in the vertebral body, the paraspinal soft tissue mass and the adjacent right rib. Circumferential epidural enhancement indicative of intra-canal spread of the infection, was also noticed. Additional MR sequences covered the level of the SCJ. Extensive subarticular and soft tissue changes with fluid collection and bone oedema of the left SCJ were shown with the typical pattern of diffuse enhancement suggestive of septic arthritis. The MR imaging findings combined with the scintigraphic findings were consistent with subacute multifocal septic arthritis involving the axial skeleton, as a pyogenic spondylodiscitis at the T9-T10 level, the left SCJ joint and the left knee joint. Subsequently, aspiration of the SCJ and the left knee joint was performed. A purulent fluid was drained and sent to microbiology. The sample revealed 96.000 cells/µL (95% neutrophils) and methicillin-resistant Staphylococcus aureus (MRSA). The patient received intravenous vancomucin (2gr. twice a day for 14 days) and subsequently the dose was adjusted to maintain the vancomucin serum levels between 17 and 20mcg/mL. The total treatment duration was 12 weeks. Four months later the patient had fully recovered and his blood tests were normal. The patient had not been referred to an oncology department yet, as the onset of the arthritis occurred about two weeks after the diagnosis of prostate cancer. In conclusion, we present a patient with known malignancy, fever, skeletal pain and multiple bone lesions in the (99m)Tc-MDP and the MRI examination, not due to metastatic disease but to septic arthritis.

Ileosigmoid fistula and delayed ileal obstruction secondary to blunt abdominal trauma: a case report.

INTRODUCTION: Abdominal trauma is a source of significant mortality and morbidity. Bowel injury as a result of blunt abdominal trauma is usually evident within hours or days of the accident. CASE PRESENTATION: A 38-year-old Caucasian Greek man presented with a subtle and delayed small bowel obstruction caused by a post-traumatic ileosigmoid fistula and ileal stricture four months after a road traffic accident. CONCLUSION: Delayed occurrence of post-traumatic small bowel stricture and ileosigmoid fistula is an uncommon surgical emergency. General surgeons as well as emergency physicians should bear this manifestation in mind should a patient return to the hospital several weeks or even years after blunt abdominal trauma with symptoms or signs of bowel obstruction.