Primary Immune Thrombocytopenic Purpura (ITP) and ITP Associated with Systemic Lupus Erythematosus: A Review of Clinical Characteristics and Treatment Modalities.

Immune thrombocytopenic purpura (ITP) is an immune-mediated disorder characterized by the destruction of platelets and megakaryocytes due to autoantibodies against the platelet surface proteins. ITP without any apparent cause of thrombocytopenia is defined as primary ITP, and ITP in the setting of SLE is secondary ITP, which can be diagnosed after excluding other causes of thrombocytopenia by history, physical examination, and laboratory testing. Patients with ITP associated with SLE have higher median platelet count and less bleeding manifestations compared to the patients with primary ITP. It can be very challenging to diagnose primary ITP in SLE patients as other causes of thrombocytopenia including drug-induced thrombocytopenia, antiphospholipid syndrome, and thrombotic microangiopathic process should be ruled out. Corticosteroids are the main modality of treatment. IVIG can be used in severe cases. Splenectomy was found to be less effective in ITP associated with SLE compared to primary ITP. Control of disease activity with immunosuppressive therapy can be helpful in some cases associated with active disease flares in SLE patients.

Transforming Acute Myeloid Leukemia Treatment Through Next-Generation Sequencing: A Single-Center Experience.

In the last decade, advancements in understanding the genetic and molecular mechanisms of acute myeloid leukemia (AML) have significantly improved treatment options. Techniques such as immunophenotyping, cytogenetics, and next-generation sequence (NGS) testing are now standard practices for patient assessments, allowing for personalized therapies based on individual patient needs. Our study aimed to evaluate the impact of cytogenetics and NGS on initial treatment decisions for AML at our institution. We analyzed the frequency of alternative therapy choices that could have been made with complete molecular and cytogenetic information and compared overall survival rates between patient groups. We also analyzed the turnaround time for result generation. Our retrospective study evaluated 39 AML patients treated at our university hospital from June 2020 to June 2022, excluding classic acute promyelocytic leukemia cases. Patients with incomplete data or concurrent hematological malignancies were excluded. We collected data on admission blood counts, European LeukemiaNet (ELN) risk stratification, Charlson score, treatment type, and timing of cytogenetics and NGS results. Patients were categorized into 'standard' or 'other therapy' groups based on their molecular and cytogenetic profiles in accordance with NCCN guidelines. Our main goal was to determine how often NGS and cytogenetics results could have influenced induction therapy choices. Secondary objectives included comparing overall survival rates and analyzing report turnaround times for NGS and cytogenetics. Our study found that out of the 39 AML patients, 17 were in the "standard" group, and 22 were in the "other therapy" group. The standard group had an average age of 62.59 years, an average time to chemotherapy initiation of 8.29 days, and an overall survival (OS) rate of 428.12 days. The other therapy group had an average age of 61.86 years, an average time to chemotherapy initiation of six days, and an OS rate of 258.64 days. There was a significant difference in survival rates between the two groups (p=0.009). According to the ELN stratification, the standard group had 11 patients at intermediate risk and six at adverse risk. In contrast, the other therapy group had seven at intermediate risk, four at good risk, and 11 at adverse risk. NGS revealed mutations in 58.97% of patients. Our study suggests that almost half of the patients could have been treated differently if complete molecular and cytogenetic information had been available before therapy initiation, highlighting the potential for more personalized treatments. Additionally, our results showed significant differences in overall survival rates between standard treatment and alternative therapy groups. Our findings emphasize the importance of timely NGS and cytogenetics result generation, guiding institutions to allocate resources for effective patient care.

Adalimumab-associated Philadelphia chromosome positive acute lymphoblastic leukaemia in a patient with Crohn's disease.

The US Food and Drug Administration has approved TNF(Tumor necrosis factor) alpha inhibitors to manage a range of inflammatory conditions, including Crohn's disease, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and other inflammatory disorders. However, these inhibitors can potentially increase the risk of secondary blood malignancies due to TNF alpha's role in various cellular processes such as angiogenesis, cell cycle proliferation, apoptosis and differentiation. In this article, we present a unique case study of a patient who developed Philadelphia-positive acute lymphoblastic leukaemia (ALL) while receiving adalimumab, a potent monoclonal antibody that specifically binds to TNF-alpha. We describe the patient's successful treatment using standard-of-care chemotherapy and tyrosine kinase inhibitors, resulting in complete remission with no measurable residual disease. Furthermore, we conducted a literature review on this subject and identified five similar cases of ALL associated with TNF alpha inhibitors.

Acute Graft Versus Host Disease After Kidney-Pancreas Transplant.

Acute graft vs. host disease (aGVHD) results from newly transplanted donor immune cells recognizing recipient tissues as foreign, leading to end-organ damage. Diagnosing aGVHD typically involves a combination of clinical evaluation, histological examination, laboratory tests, and imaging studies. Although typically associated with allogeneic stem cells transplant and less frequently with liver or small bowel transplants, solid organ transplant GVHD (SOT-GVHD) associated with kidney-pancreas transplants is exceedingly rare. Our patient presented with pancytopenia unexplained by typical causes. He developed classical aGVHD findings of fever, diarrhea, rash, and abnormal liver tests. Our case underscores the importance of keeping a broad differential when evaluating solid organ transplant patients.

Complete Remission of Advanced Hepatocellular Carcinoma in a Patient With Ulcerative Colitis Treated With Atezolizumab and Bevacizumab: A Case Report.

In this case study, a 73-year-old man who had previously undergone colectomy had a history of ulcerative colitis and alcohol abuse and presented with fatigue, weight loss, and a liver lesion. After a biopsy, he was diagnosed with stage IV-A hepatocellular carcinoma with poor differentiation and cirrhotic architecture, and molecular testing revealed positivity for multiple genes. A combination of atezolizumab and bevacizumab was administered, resulting in complete remission lasting beyond 16 months, demonstrating the potential of these drugs as a treatment option for advanced hepatocellular carcinoma (HCC). The patient's history of autoimmune conditions could have contributed to his robust response to the treatment. The report highlights the sustained survival benefits of this treatment beyond month 16.

Fibrous Dysplasia Masquerading as Sternal Malignancy: A Rare and Challenging Presentation.

This case report presents a rare and challenging manifestation of polyostotic fibrous dysplasia (FD), a skeletal developmental anomaly characterized by the proliferation of fibrous connective tissue intermingled with irregular bony trabeculae. While monostotic FD is more common, polyostotic FD can occur in the context of McCune-Albright syndrome, a multisystem developmental disorder. Our patient, a 55-year-old female with a history of diabetes, hypothyroidism, and dyslipidemia, presented with progressively worsening dysphagia, sternal pain, and swelling over three years. Clinical examination revealed a tender and hard swelling in the upper sternal area, prompting further evaluation. Laboratory results, including bone turnover markers, were unremarkable. Imaging studies unveiled a sizable anterior mediastinal lesion with heterogeneous enhancement and coarse calcifications, initially raising concerns of malignancy. Subsequent positron emission tomography scan findings confirmed FD involvement in both the sternum and right femur. Histopathology of the mediastinal mass revealed a spindle cell neoplasm with bony metaplasia, consistent with FD, supported by immunohistochemistry. A multidisciplinary team affirmed the diagnosis of polyostotic FD, and follow-up imaging after one year demonstrated no significant change in lesion size, confirming a benign etiology. While bisphosphonate therapy was planned, regrettably, the patient was lost to follow-up. This case underscores the importance of a comprehensive, multidisciplinary approach in diagnosing and managing complex presentations of FD, ultimately contributing to improved patient care and outcomes in such instances.

Visual Outcome of Plasma Exchange in Optic Neuritis Associated With Flu Vaccination: A Case Report.

Post-flu-vaccination optic neuritis is an extremely rare condition with an incidence ranging from 0.003 cases to 0.89 per 100 000 population. The exact pathophysiology is not clearly defined. Most of the patients with post-flu-vaccination optic neuritis tend to present with progressive worsening of vision in 2-3 weeks post-vaccine administration. A prompt fundus examination supplemented with MRI imaging of the orbit is required to establish the diagnosis. On diagnosis, early initiation of high-dose oral or IV steroids is recommended to prevent optic atrophy or worsening of vision. Most patients tend to have complete recovery of vision when started on steroids. However, if the patient continues to have worsening symptoms while being treated with a high dose of steroids, plasmapheresis (PLEX) is an effective intervention.

Transcatheter interventions for severe tricuspid regurgitation: a literature review.

The prevalence of tricuspid regurgitation (TR) increases with age, affecting 65%-85% of adults. Primary TR is caused by a congenital or acquired abnormality of the tricuspid valve apparatus (leaflets, chordae, papillary muscles, or annulus). Secondary TR is due to insufficient coaptation from dilation of tricuspid valve annulus due to the right ventricle (RV) or right atrium (RA) remodeling and increased RV pressures. Isolated TR is without increased RV pressures and is associated with atrial fibrillation. Mild TR is a benign disease. Moderate to severe tricuspid regurgitation has independently been associated with increased mortality. Most of these patients are treated medically due to poor outcomes with surgical repair of isolated TR. The in-hospital mortality rate is 8.8%, and the median length of stay in hospital is 11 days resulting in higher healthcare costs. Even if the patients undergo surgical repair or replacement, available data do not show improvement in survival. With a more detailed understanding of the complex anatomy and physiology of the tricuspid valve and significant complications from untreated tricuspid valve disease, the approach to the management of TR has shifted from a conservative approach to a process of prevention and intervention. In the past decade, transcatheter tricuspid valve interventions and tricuspid annuloplasty rings have been developed, contributing to decreased mortality from surgical repair. Transcatheter tricuspid valve intervention techniques have improved survival, quality of life, and reduced heart failure rehospitalization. This review summarizes normal anatomy, types of TR, etiology and different mechanisms of TR, echocardiographic assessment of the severe TR, and highlights various percutaneous transcatheter techniques for tricuspid valve repair.

Squamous cell carcinoma-A rare pancreatic exocrine malignancy.

A 65-year-old Caucasian female presented with abdominal symptoms and obstructive jaundice. She reported a significant pancreatic cancer history in her family. Her CT of the abdomen and pelvis showed 3.9 × 3.5 cm centrally necrotic mass within the pancreatic head, occluding the superior mesenteric and splenic veins; peripancreatic lymph nodes were enlarged, and there were many hepatic lesions. She underwent biopsy of the hepatic lesions showing metastatic tumor cells, arranged in the form of nests, with enlarged and hyperchromatic irregular nuclei with some nucleoli and moderate eosinophilic cytoplasm. Immunohistochemical staining on cancer cells was positive for CK7, P40, GATA3. These findings were concerning for poorly differentiated metastatic squamous cell carcinoma (SCC). PET-CT showed no other hypermetabolic lesions, suggestive of another primary except pancreatic head with SUV of 17.8, hepatic metastasis and 1 cm right retroperitoneal lymph node. The patient was diagnosed with metastatic SCC of the pancreas. Contrary to the well-known genetic mutations of pancreatic adenocarcinoma, the data on pancreatic SCC-related mutations is limited; however, one such mutation is BRCA-2 exon 15 germline mutation reported in a locally advanced SCC of the pancreas. The index patient is one of those rare cases in which a significant family history of pancreatic cancer was reported. We believe that some familial mutation could be responsible for this finding, i.e., occurrence of pancreatic cancer in multiple family members. Further research is necessary to explore such association.

Obesity Increases Risk-Adjusted Morbidity, Mortality, and Cost Following Cardiac Surgery.

BACKGROUND: Despite the epidemic rise in obesity, few studies have evaluated the effect of obesity on cost following cardiac surgery. We hypothesized that increasing body mass index (BMI) is associated with worse risk-adjusted outcomes and higher cost. METHODS AND RESULTS: Medical records for 13 637 consecutive patients who underwent coronary artery bypass grafting (9702), aortic (1535) or mitral (837) valve surgery, and combined valve-coronary artery bypass grafting (1663) procedures were extracted from a regional Society of Thoracic Surgeons certified database. Patients were stratified by BMI: normal to overweight (BMI 18.5-30), obese (BMI 30-40), and morbidly obese (BMI >40). Differences in outcomes and cost were compared between BMI strata and also modeled as a continuous function of BMI with adjustment for preoperative risk using Society of Thoracic Surgeons predictive risk indices. Morbidly obese patients incurred nearly 60% greater observed mortality than normal weight patients. Moreover, morbidly obese patients had greater than 2-fold increase in renal failure and 6.5-fold increase in deep sternal wound infection. After risk adjustment, a significant association was found between BMI and mortality (P<0.001) and major morbidity (P<0.001). The risk-adjusted odds ratio for mortality for morbidly obese patients was 1.57 (P=0.02) compared to normal patients. Importantly, risk-adjusted total hospital cost increased with BMI, with 17.2% higher costs in morbidly obese patients. CONCLUSIONS: Higher BMI is associated with increased mortality, major morbidity, and cost for hospital care. As such, BMI should be more strongly considered in risk assessment and resource allocation.

Simultaneous targeting of 5-LOX-COX and EGFR blocks progression of pancreatic ductal adenocarcinoma.

Cyclooxygenase-2 (COX-2), 5-Lipoxygenase (5-LOX), and epidermal growth factor receptor (EGRF) are over-expressed in human pancreatic ductal adenocarcinoma (PDAC). Using next-generation sequencing (NGS) analysis, we show significant increase in COX-2, 5-LOX, and EGFR expression during PDAC progression. Targeting complementary pathways will achieve better treatment efficacy than a single agent high-dose strategy that could increase risk of side effects and tumor resistance. To target COX-2, 5-LOX, and EGFR simultaneously, we tested effects of licofelone (dual 5-LOX-COX inhibitor), and gefitinib (EGFR inhibitor), individually and in combination, on pancreatic intraepithelial neoplasms (PanINs) and their progression to PDAC using genetically engineered mice. Individually, licofelone (L) and gefitinib (G) significantly inhibited incidence of PDAC in male (72% L, 90% G, p < 0.0001) and female (90% L, 85% G, p < 0.0001) mice. The combination drug treatment produced complete inhibition of PDAC in both genders. Pancreata of mice receiving combination treatment showed significantly fewer Dclk1-positive cancer stem-like cells, inhibition of COX-2, 5-LOX, PCNA, EGFR and ß-catenin expression (p < 0.05-0.0002), increased p21 expression. Significant changes in tumor immune responses and desmoplastic reaction was observed by NGS analysis in combination treatment (p < 0.05). In summary, early simultaneous targeting of 5-LOX-COX- and EGFR pathways may provide additive inhibitory effects leading to complete suppression of PDAC.