Pain Management in Multiple Myeloma Patients: A Literature Review.

Managing pain in cancer patients with multiple myeloma (MM) poses a considerable challenge. This review thoroughly investigates current pain management strategies, difficulties, and future directions in the field. The review divides pain treatment strategies into pharmaceutical and non-pharmacological therapies. Looking ahead, promising areas for future study and development are mentioned, such as incorporating precision medicine into pain management and investigating innovative therapeutics. Despite existing limitations, advances in pain management provide great opportunities to improve the quality of life and overall results for MM patients.

Advancements in MitraClip Intervention for Mitral Regurgitation: A Comprehensive Review and Comparative Analysis of Clinical Trials.

This comprehensive review explores the evolution and clinical impact of MitraClip intervention in the management of mitral regurgitation. Mitral regurgitation results from dysfunction in the mitral valve (MV) apparatus. The MitraClip Clip Delivery System was approved by the Food and Drug Administration (FDA) in 2013. The discussion delves into the procedural foundation of MitraClip intervention, primarily based on Alfieri's technique of edge-to-edge leaflet approximation. As highlighted by key clinical trials, including Endovascular Valve Edge-to-Edge Repair (EVEREST) II Trial, Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation (COAPT) Trial, and Percutaneous Repair with the MitraClip Device for Severe Functional/Secondary Mitral Regurgitation (MITRA-FR) trial, the efficacy and safety of MitraClip were evaluated in comparison to surgical interventions and guideline-directed medical therapy. Notably, the COAPT demonstrated significant benefits in reducing all-cause mortality and heart failure hospitalization, while the MITRA-FR presented contrasting results, emphasizing the importance of patient selection. An analysis of the EVEREST II trial underscores MitraClip's potential to achieve comparable outcomes to surgical intervention, emphasizing its role in reducing mitral regurgitation and improving clinical status. However, limitations and complications, such as device-related issues and the potential impact on future MV surgery, are discussed. The study also explores the evolving landscape of MV interventions, reflecting advancements and the growing acceptance of MitraClip. In conclusion, the MitraClip device represents a significant advancement in the treatment of mitral regurgitation. The data presented highlights its promising results in terms of reduced hospitalization rates, improved in-hospital mortality, and enhanced quality of life for patients. However, challenges remain, and careful consideration of patient selection and underlying pathology is crucial in determining the optimal treatment approach. Ongoing research and clinical experience will continue to refine our understanding of MitraClip's role in the evolving landscape of MV interventions.

Comprehensive Review of Mesothelioma Cases: From Diagnosis to Therapeutic Strategies.

Mesothelioma is a rare and aggressive malignancy typically associated with asbestos exposure. We present the clinical and diagnostic journey of a 63-year-old male carpenter, who presented with concerning symptoms of shortness of breath and total right lung "white-out" on imaging. Comprehensive medical evaluation revealed the presence of malignant pleural mesothelioma. This study underscores the importance of considering mesothelioma as a potential diagnosis in individuals with occupational asbestos exposure and highlights patterns in diagnosing and managing this devastating disease. Early recognition and intervention are essential in improving outcomes for patients diagnosed with mesothelioma.

Hiccups: Nerve Irritation or Masquerading as Acute Coronary Syndrome.

The typical clinical presentation of acute coronary syndrome (ACS) includes chest pain that may radiate to the left arm, shoulder, jaw, and neck, accompanied by diaphoresis, dyspnea, nausea, vomiting, and hiccups, which have been observed as the sole symptom of presentation. The mechanism of hiccups involves the activation of the vagus and phrenic nerves, leading to the activation of the diaphragm and intercostal muscles. Several hypotheses link hiccups to ACS, associating irritation of the left anterior descending artery with activation of sympathetic phrenic and vagal nerves. This case report highlights the occurrence of hiccups in patients with inferior and right ventricular myocardial infarction (MI), indicating possible nerve synapse involvement. Timely recognition of hiccups as a possible atypical symptom of ACS can facilitate early evaluation and management, preventing delays in patient care and ensuring better outcomes.

Unusual Aspergillus Pleural Effusion in a Patient With Immunodeficiency.

Pleural aspergillosis is a rare form of invasive bronchopulmonary aspergillosis that is most often seen in immunocompromised hosts. It appears because of the coagulative necrosis of lung tissue induced by the Aspergillus species, which promotes the formation of a fungal pleural effusion. We present the case of a 51-year-old liver transplant patient on chronic immunosuppression therapy who presented with respiratory failure and was found to have a large left-sided pleural effusion from invasive aspergillosis. After thoracentesis, he started antifungal therapy with isavuconazole. This newer, second-generation broad-spectrum triazole is non-inferior to voriconazole but with less hepatotoxicity and was noted to have an improvement in his symptoms. In the differential diagnosis of pulmonary effusions in immunocompromised patients, it is crucial to consider invasive aspergillosis, as demonstrated by our case. This case study highlights the importance of quick diagnosis and treatment to enhance outcomes in this vulnerable population.

IgG4 Autoimmune Disease Masquerading As Oroantral Fistula.

IgG4-related disease (IgG4-RD) is an immune-mediated disorder that involves multiple organs and is characterized by the infiltration of lymphoplasmacytic cells, including IgG4-positive plasma cells, along with storiform fibrosis and obliterative phlebitis in the inflamed organs. The primary sites affected by this condition include the pancreas, bile ducts, salivary glands, aorta, lungs, kidneys, meninges, lacrimal glands, mediastinal lymph nodes, and retroperitoneum. The pathogenesis is linked to a type 2 T-helper-cell cytokine profile and the involvement of regulatory T cells. However, the exact mechanism is still unknown. Patients with IgG4-related disease are frequently misdiagnosed as having malignancies due to the resemblance of the lesions to infections or other immune-mediated diseases and certain tumors, such as pancreatic cancer and pseudo-renal pelvis tumor. Prompt identification of IgG4-related disease is essential as a delayed diagnosis until advanced stages can result in severe organ damage and potentially fatal outcomes, despite the disease being highly responsive to treatment. This report presents a highly unusual case of IgG4-related disease (IgG4-RD) with an atypical presentation in a 38-year-old female patient. The patient sought medical attention in the emergency department due to nasal septal erosions and an oral-antral fistula. Nasal cultures were conducted and indicated the presence of Klebsiella ozaena. Subsequent investigations, including a nasal biopsy, confirmed the diagnosis of IgG4-related autoimmune disease.

An Atypical Presentation of Chronic Inflammatory Myelin Degeneration in Neuromyelitis Optica (NMO).

Neuromyelitis optica (NMO) is an autoimmune disorder characterized by aquaporin-4 (AQP4) IgG autoantibodies. These autoantibodies induce chronic neuroinflammatory damage to the spinal cord and optic nerve. NMO clinically manifests as relapsing and overlapping neurodegenerative episodes of optic neuritis (ON) and transverse myelitis (TM). Contrasting from other autoimmune neurodegenerative disorders, NMO has a poor prognostic profile often involving permanent neurological disability. We present a case of a 65-year-old male who presented with a progressive weakening in his left upper and lower extremities with reduced sensation and was found to have an acute flare of NMO. We explore the broad symptomatology involved in the disorder along with relevant crucial imaging findings pointing toward the diagnosis of NMO. Finally, we discuss treatment modalities in the context of our patient's clinical course and prognostic factors. Early intervention and suppression of relapse in this neuroinflammatory neurodegenerative disorder can help decrease the duration of acute flares and improve long-term outcomes for patients affected by NMO.

Dieulafoy's Lesion of the Duodenum: A Rare and Fatal Cause of Gastrointestinal Bleed.

Dieulafoy's lesion (DL) is an unusual cause of recurrent gastrointestinal bleeding that can be fatal. It can occur in various parts of the gastrointestinal (GI) tract, most commonly located in the stomach, especially at the level of lesser curvature; however, it can occur in other parts, including the colon, esophagus, and duodenum. A duodenal Dieulafoy lesion is characterized by the presence of a larger-caliber artery that protrudes through the GI mucosa and can lead to massive hemorrhage. The exact cause of DL is yet to be determined. Clinical presentation includes painless upper GI bleeding, including melena, hematochezia, and hematemesis, or rarely iron deficiency anemia (IDA); however, most of the patients are asymptomatic. Some patients also have non-gastrointestinal comorbidities such as hypertension, diabetes, and chronic kidney disease (CKD). The diagnosis is established by esophagogastroduodenoscopy (EGD), which includes the presence of micro pulsatile streaming from a mucosal defect, the appearance of a fresh, densely adherent clot with a narrow point of attachment to a minute mucosal defect, and the visualization of a protruding vessel with or without bleeding. Initial EGD can be non-diagnostic due to the relatively small size of the lesion. Other diagnostic modalities include endoscopic ultrasound and mesenteric angiography. The treatment of duodenal DL includes thermal electrocoagulation, local epinephrine injection, sclerotherapy, banding, and hemoclipping. We present here a case of a 71-year-old female who had a history of severe IDA requiring multiple blood transfusions and intravenous iron in the past and was found to have duodenal DL.

Transcatheter Closure of Atrial Septal Defect: A Review of Currently Used Devices.

Over the past seven decades, significant advancements and innovations have occurred in the field of percutaneous atrial septal defect (ASD) closure using transcatheter-based devices. This article focuses on the current literature surrounding the three Food and Drug Administration (FDA)-approved devices for ASD and patent foramen ovale (PFO) closure in the United States, namely, the Amplatzer Septal Occluder (ASO), Amplatzer Cribriform Occluder, and Gore Cardioform ASD Occluder. The ASO has been widely used since its FDA approval in 2001. Studies have shown its high success rate in closing ASDs, especially small-sized defects. The RESPECT trial demonstrated that PFO closure using the ASO reduced the risk of recurrent ischemic stroke compared to medical therapy alone. The Closure of Atrial Septal Defects With the Amplatzer Septal Occluder Post-Approval Study (ASD PMS II) evaluated the safety and effectiveness of ASO in a large cohort of patients, reporting a high closure success rate and rare hemodynamic compromise. The Amplatzer Cribriform Occluder is designed for the closure of multifenestrated ASDs and has shown promising results in small-scale studies. It successfully closed the majority of fenestrated ASDs, leading to improved right ventricular diastolic pressure without major complications. The REDUCE trial compared PFO closure using the Gore Helex Septal Occluder and Gore Cardioform Septal Occluder with antiplatelet therapy alone. The study demonstrated that PFO closure significantly reduced the risk of recurrent stroke and brain infarction compared to antiplatelet therapy alone. However, the closure group had a higher incidence of atrial fibrillation or atrial flutter. There is a risk of atrial fibrillation with the use of ASO as well. The FDA-approved Gore Cardioform ASD Occluder showed excellent performance in the ASSURED clinical study. The device achieved high technical success and closure rates, with low rates of serious adverse events and device-related complications. A meta-analysis comparing transcatheter ASD closure with surgical closure revealed that the transcatheter approach had a high success rate, lower rates of adverse events, and shorter hospital stays compared to surgery, without any mortality. Complications associated with transcatheter ASD closure have been reported, including femoral arteriovenous fistulas, device embolization, cardiac erosion, aortic incompetence, and new-onset migraine. However, these complications are relatively rare. In conclusion, transcatheter ASD closure using FDA-approved devices has proven to be safe and effective in the majority of cases. These devices offer excellent closure rates, reduced risk of recurrent stroke, and shorter hospital stays compared to surgery. However, careful patient selection and follow-up are necessary to minimize complications and ensure optimal outcomes.

Unveiling the Truth: Diagnosing Bacterial Meningitis Through Repeat Lumbar Punctures.

Bacterial meningitis is a cause of global concern given its associated high rates of mortality and complications. Timely diagnosis and management are crucial in improving outcomes in patients. Lumbar puncture and radiological investigations form the crux of diagnosis. However, the clinical course becomes complicated if lumbar puncture results are unrevealing and equivocal for bacterial meningitis. We present a case of a 60-year-old female who was diagnosed with bacterial meningitis on repeated lumbar puncture. Clinical vigilance and a high degree of suspicion is needed to ensure that patients with bacterial meningitis are diagnosed and managed appropriately, especially in cases with inconclusive lumbar puncture or radiological investigations.

Chylothorax: A Late Complication of Disseminated Mycobacterium avium Complex (MAC) Infection.

Chylothorax is a rare cause of pleural effusion and occurs due to leakage of chyle into the pleural space. In most cases, it results from trauma, with malignancy accounting for most of the non-traumatic causes. Chylothorax resulting from immune reconstitution inflammatory syndrome (IRIS), during treatment of Mycobacterium avium complex (MAC) infection, is an extremely infrequent cause of chylothorax, with only a handful of cases reported in the literature.

Hemophagocytic Lymphohistiocytosis and Hodgkin Lymphoma in a Newly Diagnosed HIV Patient: A Diagnostic Dilemma.

Hemophagocytic lymphohistiocytosis (HLH) is a severe hyperinflammatory syndrome that arises due to a dysregulated immune response caused by the aberrant activation of lymphocytes and macrophages. In this rare case report, we describe a newly diagnosed human immunodeficiency virus (HIV) patient who was found to have Epstein-Barr virus (EBV) provoked HLH and co-existing Hodgkin lymphoma (HL).  Our patient was a 28-year-old newly diagnosed HIV patient who presented with nonspecific symptoms, including bilateral foot pain and tingling sensation. Laboratory findings were significant for pancytopenia. With a high index of suspicion, the patient had a bone marrow biopsy done which confirmed a diagnosis of both HLH and Hodgkin's lymphoma. The case highlighted the diagnostic dilemma of HLH in the setting of HIV infection. Identifying the major components of his disease process was pivotal to ensure that the patient was commenced on appropriate therapy for the EBV-driven HLH and HL.  The diagnosis of HLH in newly diagnosed HIV remains challenging due to the diverse clinical presentations and the need to exclude other possible causes. The clinical features of HLH, HL, and HIV can be nonspecific and overlap, creating a diagnostic dilemma. Diagnosis requires a combination of clinical, laboratory, and histopathological features. The management in such cases requires prompt diagnosis through a multidisciplinary approach, a variety of chemotherapy, immunosuppression, supportive care, and treatment of the underlying triggers.

A 35-Year-Old Female With a Lupus Flare Presenting as Cardiac Tamponade: A Case Report.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder that affects multiple organ systems, significantly impacting the cardiovascular system. One potential complication of acute SLE flare is the development of pericardial effusion which can lead to potentially life-threatening consequences if not promptly identified. In this report, we describe the case of a 35-year-old female with a known history of SLE who developed rapid-onset, large-volume pericardial effusion with tamponade during a lupus flare. She received emergency treatment involving pericardiocentesis and was administered high doses of glucocorticoid and immunosuppressive medication. As a result, the pericardial effusion gradually resolved, and the patient's symptoms improved. This case emphasizes the significance of immediately identifying and managing swiftly progressing pericardial effusion in SLE patients. This is crucial as it can lead to severe and potentially lethal complications.

COVID-19-Induced Myopathy and Diaphragmatic Weakness: A Case Report.

Coronavirus disease 2019 (COVID-19) is a respiratory illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus that can induce myopathy, which can evolve into potentially life-threatening muscle weakness, including diaphragmatic paralysis. We present a case report of a 57-year-old female treated in the medical ICU for acute respiratory distress syndrome (ARDS) triggered by active COVID-19 infection, who subsequently developed worsening respiratory weakness from underlying COVID-19 myopathy manifesting as respiratory muscle weakness. Our patient's muscle biopsy highlights the development of muscle atrophy without evidence of inflammatory myopathy, making the presence of pre-existing autoimmune myopathy unlikely. While literature cites different biochemical etiologies for the development of myopathy, the exact mechanism behind this phenomenon is not yet defined.

Ischemic Colitis or Colon Cancer: A Diagnostic Dilemma.

Ischemic colitis, a potentially reversible pathology of the colon, can masquerade in its presentation as colonic carcinoma. It typically presents with cramping abdominal pain, diarrhea, and per-rectal bleeding. Colonoscopy remains the diagnostic modality of choice that typically shows friable, edematous, or erythematous mucosa with scattered hemorrhagic erosions or ulcerations. Although rare, the colonoscopic findings can sometimes reveal a tumor mass that confounds the diagnosis of ischemic colitis as colonic carcinoma. Our patient was a 78-year-old female with no previous colon cancer screening who presented with a mass-forming variant of ischemic colitis. Due to the overlap in presentations, radiographic findings, and colonoscopic findings, the diagnostic challenge was evident. Ultimately, colon cancer was ruled out through thorough colonoscopic follow-up and biopsy-guided pathological analysis. This case signifies the importance of considering colonic mass as a guise of underlying ischemic colitis to ensure an accurate diagnosis and the best possible outcome for the patient.

A Pangenome Approach for Discerning Species-Unique Gene Markers for Identifications of Streptococcus pneumoniae and Streptococcus pseudopneumoniae.

Correct identifications of isolates and strains of the Mitis-Group of the genus Streptococcus are particularly difficult, due to high genetic similarity, resulting from horizontal gene transfer and homologous recombination, and unreliable phenotypic and genotypic biomarkers for differentiating the species. Streptococcus pneumoniae and Streptococcus pseudopneumoniae are the most closely related species of the clade. In this study, publicly-available genome sequences for Streptococcus pneumoniae and S. pseudopneumoniae were analyzed, using a pangenomic approach, to find candidates for species-unique gene markers; ten species-unique genes for S. pneumoniae and nine for S. pseudopneumoniae were identified. These species-unique gene marker candidates were verified by PCR assays for identifying S. pneumoniae and S. pseudopneumoniae strains isolated from clinical samples. All determined species-level unique gene markers for S. pneumoniae were detected in all S. pneumoniae clinical isolates, whereas fewer of the unique S. pseudopneumoniae gene markers were present in more than 95% of the clinical isolates. In parallel, taxonomic identifications of the clinical isolates were confirmed, using conventional optochin sensitivity testing, targeted PCR-detection for the "Xisco" gene, as well as genomic ANIb similarity analyses for the genome sequences of selected strains. Using mass spectrometry-proteomics, species-specific peptide matches were observed for four of the S. pneumoniae gene markers and for three of the S. pseudopneumoniae gene markers. Application of multiple species-level unique biomarkers of S. pneumoniae and S. pseudopneumoniae, is proposed as a protocol for the routine clinical laboratory for improved, reliable differentiation, and identification of these pathogenic and commensal species.

Validation of a high-performance liquid chromatography method for thiopurine S-methyltransferase activity in whole blood using 6-mercaptopurine as substrate.

BACKGROUND: Variation in metabolism, toxicity and therapeutic efficacy of thiopurine drugs is largely influenced by genetic polymorphisms in the thiopurine S-methyltransferase (TPMT) gene. Determination of TPMT activity is routinely performed in patients to adjust drug therapy. METHODS: We further optimized a previously established high-performance liquid chromatography (HPLC) method by measuring TPMT activity in whole blood instead of isolated erythrocytes, which is based on conversion of 6-mercaptopurine to 6-methylmercaptopurine using S-adenosyl-methionine as methyl donor. RESULTS: The simplified TPMT whole-blood method showed similar or better analytical and diagnostic performance compared with the former erythrocyte assay. The whole-blood method was linear for TPMT activities between 0 and 40 nmol/(mL·h) with a quantification limit of 0.1 nmol/(mL·h). Within-day imprecision and between-day imprecision were ≤5.1% and ≤8.5%, respectively. The optimized method determining TPMT activity in whole blood (y) showed agreement with the former method determining TPMT activity in erythrocytes (x) (n=45, y=1.218+0.882x; p>0.05). Phenotype-genotype concordance (n=300) of the whole-blood method was better when TPMT activity was expressed per volume of whole blood (specificity 92.2%), whereas correction for hematocrit resulted in lower genotype concordance (specificity 86.9%). A new cutoff for the whole-blood method to distinguish normal from reduced TPMT activity was determined at ≤6.7 nmol/(mL·h). CONCLUSIONS: This optimized TPMT phenotyping assay from whole blood using 6-MP as substrate is suitable for research and routine clinical analysis.