The role of immunotherapy plus chemotherapy versus chemotherapy alone as first-line treatment for advanced non-small cell lung cancer: an updated systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Recently published randomized controlled trials (RCTs) showed improved overall survival (OS) and progression-free survival (PFS) with the combination of immunotherapy and chemotherapy as compared to chemotherapy alone in advanced non-small cell lung cancer (NSCLC). We aimed to provide a systematic review and meta-analysis of RCTs regarding the efficacy and safety of immunotherapy and chemotherapy combinations for advanced NSCLC. METHODS: On December 23rd, 2021, we searched databases for RCTs that reported PFS and OS as primary outcomes. RESULTS: We included 11 RCTs with 6,386 patients (3,850 in the combination therapy group and 2,536 in the chemotherapy group). Combination therapy was associated with an improvement in PFS (HR: 0.60; 95% CI: 0.54, 0.66; P < 0.00001) andOS (HR: 0.77; 95% CI: 0.68, 0.87; P ≤ 0.0001), compared to chemotherapy. There were no significant differences between both groups in terms of treatment-related adverse events (TRAEs) (RR: 1.07; 95% CI: 0.99, 1.16; P = 0.09). CONCLUSION: The combination of immunotherapy and chemotherapy as first-line treatment for advanced NSCLC significantly improved PFS and OS compared to chemotherapy alone without a significant increase in the overall TRAEs.

Restrictive versus Liberal Blood Transfusion Strategy in Patients With Acute Myocardial Infarction: A Meta-Analysis of Randomized Clinical Trials.

Background: A meta-analysis of observational studies comparing differences in outcomes between restrictive blood transfusion (RBT) and liberal blood transfusion (LBT) in patients with acute myocardial infarction (AMI) reported that LBT is associated with higher all-cause mortality. Few randomized clinical trials (RCTs) have compared RBT to LBT in patients with AMI and anemia, but no meta-analysis of RCTs was performed to date. Aim: To assess the clinical effect of RBT compared to LBT in patients with AMI and anemia regarding was all-cause mortality, recurrent MI, revascularization, and heart failure exacerbation. Methods: The electronic databases Ovid MEDLINE, EMBASE, Cochrane Central, Scopus, and Google Scholar, were systematically searched to identify eligible studies published before June 19th, 2021. RCTs that assessed the effect of RBT compared to LBT were included. The primary endpoint was all-cause mortality. Secondary endpoints included recurrent MI, revascularization, and heart failure exacerbation. Results: Three RCTs with 821 patients were included (421 received RBT, and 400 received LBT). The mean age was 75.9 ± 6.1 years, and 56% were male. Our meta-analysis showed that RBT was not associated with reduced all-cause mortality (RR = 1.61; 95% CI = 0.38-6.96, p = 0.52), recurrent MI (RR = 0.98; 95% CI = 0.48-1.96, p = 0.94), revascularization (RR = 1.18; 95% CI = 0.26-5.44, p = 0.83) and heart failure exacerbation (RR = 0.86; 95% CI = 0.23-3.22, p = 0.82) when compared to LBT. Conclusion: RBT was not associated with reduced all-cause mortality, recurrence of MI, need for revascularization, or heart failure exacerbation in patients with AMI and anemia compared to LBT. A larger RCT is required to confirm the above findings.

Early presentation of pembrolizumab-associated pneumonitis.

Pembrolizumab is a selective anti-PD-L1 humanised monoclonal antibody approved by the Food and Drug Administration for treating multiple cancers, including cervical cancer, non-small cell lung cancer (NSCLC), renal cell carcinoma, bladder cancer, and squamous head and neck cancer. Pneumonitis is a rare but known complication of pembrolizumab treatment for NSCLC. The median time frame of its appearance is 2.8 months. However, we present a case of pneumonitis appearing within 48 hours. The patient presented with rapidly progressive respiratory failure, and imaging demonstrated diffuse bilateral patchy involvement of the upper lung lobe and pre-hilar regions, which likely indicate pneumonitis. Because of likely grade 3 pneumonitis, he was treated with steroids and showed immediate improvement of symptoms. Repeated CT imaging showed resolution of bilateral patchy infiltrates. He was discharged to the rehabilitation unit. Rapid recognition of pneumonitis as a side effect of pembrolizumab is important because early treatment can help prevent respiratory failure and possible death.

Primary soft tissue sarcoma: stage IV extranodal T-cell non-Hodgkin's lymphoma.

Non-Hodgkin's lymphoma (NHL) presenting as a soft tissue sarcoma is rare, occurring at a rate of 0.11%. Peripheral T-cell lymphomas comprise 4% of all NHLs. We report the case of a 49-year-old Caucasian man who presented with a mass in the medial aspect of the thigh. Ultrasound showed a complex subcutaneous mass. MRI demonstrated a superficial complex skeletal mass affecting the sartorius muscle with other lesions involving the femur and the gluteus maximus. Positron emission tomography-computed tomography (PET-CT) showed diffuse pulmonary metastases with no involvement of nodes, liver, spleen with high suspicion of advanced sarcoma. Core biopsy revealed a T-cell NHL, and staining was positive for anaplastic lymphoma kinase. The patient received six cycles of cyclophosphamide, doxorubicin, vincristine, etoposide and prednisone. Repeat PET-CT showed reduction in the mass, with no fluorodeoxyglucose-avid uptake. Latest MRI showed near-normal intensity. Further PET-CTs determine disease remission or progression.

Multi-gene mutation metastatic castrate-resistant prostate cancer.

Gene panel sequencing of metastatic castrate-resistant prostate cancer (mCRPC) can assist in identifying appropriate targeted therapies. Although some studies have reported single DNA mutations, this is the first case of mCRPC with five different DNA mutations based on gene panel analysis. The patient, a 75-year-old man, initially presented with haematuria. Laboratory investigation revealed elevated prostate-specific antigen levels, and CT showed an enlarged prostate gland with metastatic lymph nodes. A 12-core biopsy revealed adenocarcinoma of the prostate. Gene panel sequencing demonstrated five different DNA mutations associated with sensitivities to olaparib and pembrolizumab. Treatment failure after hormonal therapy with leuprorelin and bicalutamide resulted in the initiation of chemotherapy with docetaxel. Over the past decade, development of genome sequencing analysis may guide us with more precise targeted therapy specific to mCRPC early on, especially with poly (ADP-ribose) polymerase inhibitors may show survival benefits.

A Novel Case of Cytomegalovirus Pneumonia in an Acquired Thrombotic Thrombocytopenic Purpura Patient Treated With Rituximab.

Thrombotic thrombocytopenic purpura (TTP) is thrombotic microangiopathy that is universally fatal if not promptly recognized and treated. Standard treatment includes plasma exchange (PLEX) therapy and immunosuppression. We present a case of an 80 years old African American male with a past medical history significant for essential hypertension, chronic obstructive pulmonary disease, and a recent TTP diagnosis for which he was treated with PLEX, glucocorticoids, and rituximab. The patient presented with complaints of shortness of breath of four days duration. He was hypoxemic on presentation; other vital signs were within normal limits. The basic metabolic panel and complete blood count were unremarkable. A computed tomography (CT) of the chest with contrast showed right lower lobe segmental and subsegmental pulmonary emboli. He was initiated on intravenous heparin therapy. During hospitalization, he had progressive clinical deterioration with progressive hypoxemia. A repeat CT scan demonstrated bilateral pulmonary infiltrates. The patient underwent bronchoscopy due to concerns of opportunistic infections in view of his recent immunosuppressive treatment. Bronchoalveolar lavage revealed cytomegalovirus (CMV), and the patient was initiated on ganciclovir. CMV pneumonia has been reported after rituximab therapy in patients with lymphomas and lymphoproliferative disorders. To our knowledge, this is the first case of CMV pneumonia after rituximab therapy in a patient with TTP.

Dysphagia as the Presenting Symptom of Laryngeal Tuberculosis.

Laryngeal tuberculosis (TB) is a rare form of tuberculosis that most commonly presents with dysphagia and weight loss. We report a case of a 75-year-old Vietnamese male who presented with dysphagia, odynophagia, and a 30-pound weight loss over the two months prior to presentation. Nasopharyngeal evaluation with microdirect laryngoscopy was performed as part of the workup and revealed lesions of the epiglottis and left vocal cord. A tissue biopsy and quantiferon testing confirmed the diagnosis of tuberculosis. The patient was started on quadruple therapy and is currently receiving treatment. This case highlights the need for consideration of the rare, yet important, differential of laryngeal TB in patients presenting with non-specific complaints such as dysphagia and weight loss.

The Value of Screening for Bicuspid Aortic Valve in First Degree Family Members.

A 54-year-old male with a history of hypertension, diabetes, and sleep apnea presented with a two-week history of dyspnea. The patient was hypoxic with bilateral leg edema. Initial workup showed elevated troponin at 0.15 ng/mL, brain natriuretic peptide of 720 pg/mL, and hyponatremia. Chest X-ray revealed lungs infiltrates with possible pneumonia. An electrocardiogram showed sinus tachycardia and ST depression in septal leads. He received diuretics and antibiotics for fluid overload and pneumonia. Blood culture showed methicillin-sensitive staphylococcus aureus (MSSA). Transthoracic echocardiogram (TTE) revealed a left ventricle ejection fraction (LVEF) of 55-60%, a bicuspid aortic valve (BAV) with mild aortic stenosis and calcification, and an ascending aortic aneurysm of 4.2 cm, though no vegetations. A transesophageal echocardiogram (TEE) demonstrated the BAV, 1.4 cm mobile vegetation, an abscess on the aortic annulus, severe aortic regurgitation, and 4.6 cm ascending aortic aneurysm. He underwent aortic valve replacement, ascending aortoplasty, and coronary artery bypass grafting. He was discharged with eight weeks of antibiotics after a good recovery with resolution of fever, dyspnea, and bacteremia. His son was diagnosed with BAV earlier. Consequently, by screening echocardiogram and education, our patient could have avoided complications of severe infective endocarditis.

Extracorporeal Membrane Oxygenation (ECMO): A Life Saver in Near-Fatal Asthma.

Near-fatal asthma (NFA) is a life-threatening condition that represents the most severe clinical phenotype of asthma and can progress to fatal asthma. Patients with NFA do not respond adequately to conventional medical therapy and urgent intervention is needed to provide adequate oxygenation by invasive mechanical ventilation. While mechanical ventilation is a potentially life-saving intervention, it could cause lung injury, barotrauma, and dynamic hyperinflation due to high ventilator settings resulting in hemodynamic instability. Extracorporeal membrane oxygenation (ECMO) provides full respiratory support with adequate gas exchange in patients with NFA and improves survival rate. We present a case of a young female patient who presented with NFA, and her clinical condition was worsening despite invasive positive pressure mechanical ventilation.

Unusual Cause of Stroke.

Every year, more than 795,000 people in the United States have a stroke, the vast majority of which are ischemic. Cardiac myxoma is an unusual cause of stroke and accounts for less than 1% of ischemic strokes. We present a case of a 56-year-old male with a history of hypertension, dyslipidemia, and type 2 diabetes mellitus, who presented with altered mental status, tinnitus, double vision, and diaphoresis. Due to concern for a cerebral vascular accident, a CT scan of the brain was obtained and showed no acute intracranial process. Brain MRI revealed multiple small acute infarcts involving bilateral posterior cerebral artery distribution. Further evaluation included transthoracic echocardiography that showed a large mobile mass in the left atrium measuring 3.5 x 2 cm intermittently projecting through the mitral valve. The patient underwent successful surgical resection of the left atrial mass. The pathology report confirmed the diagnosis of atrial myxoma. This case further highlights the importance of complete evaluation of stroke, including echocardiography, as well as the importance of careful surgical resection to prevent recurrence of systemic embolization and other complications of atrial myxoma.

Spodick's Sign: A Case Report and Review of Literature.

Acute pericarditis is commonly diagnosed in patients who present with chest pain. Accurate diagnosis of acute pericarditis is essential because of its relative similarity to ST-elevation myocardial infarction (STEMI) in both clinical presentation and electrocardiogram (EKG) changes. Additionally, troponin elevation is occasionally seen in acute pericarditis due to myocardial involvement (myopericarditis), which makes accurate diagnosis more challenging. A 12-lead EKG remains the most useful diagnostic test in differentiating acute pericarditis from STEMI. Spodick's sign is a less recognized electrocardiographic feature of acute pericarditis and is frequently overlooked by clinicians. We present a case of a 52-year-old male who initially presented with acute onset substernal chest pain. His EKG revealed diffuse subtle ST elevation and downsloping TP segment (Spodick's sign). A coronary angiogram demonstrated normal coronaries which eliminated the possibility of coronary artery disease. In this article, we will discuss how to differentiate between acute pericarditis and myocardial infarction, with a focus on Spodick's sign, amongst other EKG findings suggestive of pericarditis.

An HIV Associated Plasmablastic Lymphoma With Spontaneous Tumor Lysis Syndrome.

Plasmablastic lymphoma (PBL) is a rare and aggressive B-cell Non-Hodgkin lymphoma (NHL) associated with immunocompromised states such as HIV. We present a case of PBL in an HIV patient presenting as spontaneous tumor lysis syndrome and discuss the clinical challenges hence encountered.