The Prognostic Significance of Peripheral Blood Biomarkers in Patients With Advanced Non-Small Cell Lung Cancer Treated With Pembrolizumab: A Clinical Study.

Systemic inflammation has long been associated with poor outcomes in many types of solid tumors. Peripheral blood biomarkers, such as absolute lymphocyte count (ALC) and the ratio of absolute neutrophil count to absolute lymphocyte count (ANC/ALC), have been shown to be immune-inflammatory parameters highlighting an individual's immune status. The prognostic role of ALC and ANC/ALC on overall survival (OS) was examined in patients with advanced non-small cell lung carcinoma (NSCLC) receiving pembrolizumab. Of a total of 239 patients, 52% were male, with a median age of 67 years (interquartile range [IQR], 59-73). Most patients had a diagnosis of adenocarcinoma (76%), with stage IV disease (82%). PD-L1 expression was >50% in 44% of the patients. The median time on treatment with pembrolizumab was 5.8 months (IQR, 2.9-12.7). An ANC/ALC <5 was associated with improved OS at initiation of pembrolizumab (P = .002), whereas an ALC >1.4 deciliter (dL) trended toward improved OS compared with ALC <1.4 dL (P = .053). After adjusting for potential cofounders with a multivariate analysis, a baseline ANC/ALC of 5 or higher was associated with a significantly increased risk of death (HR, 1.93; 95% CI, 1.27-2.93; P = .002). An ANC/ALC <5 at the time of initiation of treatment with pembrolizumab was associated with improved OS in patients with advanced NSCLC. The median ALC and ANC/ALC were significantly lower after 6 weeks of treatment with pembrolizumab.

Vitamin B12 Deficiency Mimicking Thrombotic Thrombocytopenic Purpura: A Case Report and Review of Literature.

Vitamin B12 (cyanocobalamin) deficiency can lead to ineffective erythropoiesis, intramedullary hemolysis, and, in severe cases, neurologic deficits. Some of those findings are also features of thrombotic microangiopathies, specifically thrombotic thrombocytopenic purpura (TTP), and the distinction between both entities could sometimes be challenging. While the treatment of the former consists of enteral or parenteral repletion, the treatment of TTP is more complex and time-sensitive. For that reason, refining diagnostic strategies is crucial to avoid misdiagnosis and unnecessary interventions. Here is an example of a potential life-threatening hemolysis caused by vitamin B12 deficiency with acute onset neurologic symptoms, which resolved with B12 repletion.

Tumour-To-Tumour Metastasis: A Rare Case of Prostate Cancer Metastasising to Primary Lung Adenocarcinoma.

Tumour-to-tumour metastasis (TTM) is a rare phenomenon that clinicians should be aware of when evaluating patients with a history of prostate cancer. We present the diagnosis and management of an 80-year-old former smoker with high-risk prostate cancer, who developed a lung nodule consistent with TTM. The patient had concurrent primary lung adenocarcinoma and metastatic prostate cancer, making this a unique case of dual primary and metastatic malignancies. The complexity of this case highlights the need for comprehensive evaluation and interdisciplinary management in patients with multiple malignancies. The literature review reveals that these are extremely rare occurrences, with most cases involving metastasis to the second primary tumour. Despite the challenges in diagnosing preoperatively, it is important to consider TTM as a possibility in patients with prostate cancer who present with a lung nodule. This report presents one of the few documented cases of TTM. It also reviews relevant cases in the literature and discusses the current situation in relation to established criteria for classifying combination tumours. LEARNING POINTS: Isolated lung metastasis with prostate cancer is exceptionally rare in the literature.Tumour-to-tumour metastasis cases present challenges in sampling and interpreting histopathology.In instances of tumour-to-tumour metastasis, it is vital to consider the patient's clinical history, perform thorough gross examination and obtain appropriate samples to distinguish between the separate tumour components.

The Clinical Value of Methicillin-Resistant Staphylococcus aureus Nasal Screening in the Management of Diabetic Foot Infections.

Nasal carriage of methicillin-resistant Staphylococcus aureus (MRSA) remains an important risk factor for diabetic foot infections (DFIs). We explored herein the clinical value of MRSA-nasal screening in the management of DFIs. In this retrospective case-control study, patients admitted with a DFI between 1/1/2014-6/30/2020 were studied and divided into cases (positive MRSA-nasal screening) and controls (negative MRSA-nasal). We included 171 patients (22 cases and 149 controls). MRSA nasal screening had a negative predictive value (NPV) of 86%. Compared to controls, cases were treated with intravenous vancomycin for a longer duration: (median [IQR], 5[3,11] vs 2[2,6]) days, P = .037). In multivariate analysis, a negative MRSA nasal screening was associated with a 74% decreased risk of AKI (OR = 0.26, 95% CI = 0.07-0.89). MRSA nasal screening in patients admitted with DFI has a high NPV. Obtained early, it can shorten the duration of intravenous vancomycin, consequently preventing AKI.

Recurrent Nasal-Type Extranodal Natural Killer/T-Cell Lymphoma with Meningeal Involvement.

Extranodal natural killer/T-cell lymphoma nasal type (NNKTL) is a type of non-Hodgkin's lymphoma that has been associated with Epstein-Barr virus (EBV). It has an aggressive behavior, known for predilection to metastasize to different organs. Central nervous system (CNS) spread from a primary location has been reported. Different modalities of treatment such as chemotherapy and radiation therapy have been employed in the management of this disease. Severe toxicities of currently available treatment have made clinicians seek more targeted therapies using molecular profiling. We present a 44-year-old Hispanic patient who was diagnosed with an early-stage NNKTL and treated with the modified SMILE regimen for 6 cycles. His EBV DNA PCR turned undetectable and remained so throughout the treatment. He sustained complete right vision loss due to right optic nerve invasion by the tumor, leading to prophylactic intravitreal methotrexate to the contralateral eye. The patient achieved good response with minimal residual disease. He was supposed to start radiation as a sequential therapy. However, the acute development of severe headache and confusion lead to a complete workup showing leptomeningeal spread. He eventually succumbed to the disease.

Bevacizumab-Induced Pneumonitis in a Patient With Metastatic Colon Cancer: A Case Report.

Bevacizumab is a vascular endothelial growth factor-directed humanized monoclonal antibody used to treat many types of cancer and some eye diseases. Due to inhibition of angiogenesis, many adverse reactions such as bowel necrosis, nasal septal perforation, and renal thrombotic microangiopathy have been described. However, its association with interstitial pneumonitis is scarcely reported in the literature. We report a case of a 79-year-old woman with metastatic colon cancer who presented with cough and dyspnea on exertion the day after initiation of bevacizumab. She was found to have bilateral airspace opacities on imaging. Infectious and cardiogenic etiologies of dyspnea were ruled out. Due to the temporal relationship with the initiation of chemotherapy, she was suspected to have developed bevacizumab-induced interstitial pneumonitis. She improved rapidly with high-dose steroids. Follow-up imaging showed resolution of infiltrates. This is the first reported case in the literature that directly links bevacizumab to interstitial pneumonitis.

Neutropenic Enterocolitis Secondary to Sulfasalazine in a Woman With Psoriatic Arthritis.

Neutropenic enterocolitis (NE) also known as typhlitis is a serious condition that has been described in immunosuppressed hosts including patients with leukemia, HIV and in patients on chemotherapy. We present the first case of female on sulfasalazine for psoriatic arthritis, otherwise healthy, who was diagnosed with NE involving the cecum and rectum. This adds up to the cases of NE diagnosed in nononcologic conditions. A 65-year-old female with a history of psoriatic arthritis on sulfasalazine, presented to the emergency department (ED) after an episode of syncope. She was complaining of a fever and mild generalized abdominal pain. Physical exam was remarkable for peri-umbilical tenderness. Severe neutropenia and acute kidney injury were found on blood work. CT scan of the abdomen showed evidence of colitis, involving the cecum, ascending colon and rectum, which in light of neutropenia was consistent with NE. Clostridium difficile colitis was ruled out. Intravenous fluids and broad-spectrum antibiotics were initiated, and sulfasalazine was discontinued. The patient was subsequently afebrile and was out of neutropenia by day 3 without the need for granulocyte-macrophage colony-stimulating factor (GM-CSF). By day 5, the patient was pain free and was discharged. Even though NE is primarily described in the setting of malignancies and chemotherapy, one should keep in mind that this entity can occur in people on any immunosuppressive therapy. Early discontinuation of sulfasalazine and conservative management were essential in the treatment of NE in this case. Whether neutropenia precipitates colitis or the latter causes agranulocytosis by bone marrow suppression through cytokines remains to be proved. The diagnosis of medication-related adverse reactions remains a big challenge for clinicians and therefore requires a high index of suspicion. Resolution of the symptoms can simply occur with the discontinuation of the offending drug and often does not require extensive workup or treatments that might cause harm to the patient's health.

Third-Generation Human Epidermal Growth Factor Receptor 2 Chimeric Antigen Receptor Expression on Human T Cells Improves with Two-Signal Activation.

Patient derived T cells activated ex vivo with CD3/CD28 beads show superior expansion. Therefore, CD3/CD28 beads have huge potential to be used in the clinic for immunotherapy applications. Two protocols were devised to evaluate if the expression of third-generation human epidermal growth factor receptor 2 chimeric antigen receptor (CAR) can be improved on human T cells activated with CD3/CD28 beads. In protocol 1, unconcentrated human epidermal growth factor receptor 2 CAR retroviral supernatants were used, and in protocol 2, concentrated virus was used. The results demonstrate that compared to unconcentrated viral supernatants, transduction with the concentrated virus improved the infection rate of bead activated CD4 T cells from ∼40% to ∼70%, and the fluorescent intensity values improved from ∼12,000 to ∼28,000 mean fluorescence intensity units. These results demonstrate the utility of these protocols for CAR immunotherapies.