Mechanical ventilation can induce organ injury associated with overwhelming inflammatory responses. Excessive activation of poly(adenosine diphosphate-ribose) polymerase enzyme after massive DNA ...damage may aggravate inflammatory responses. Therefore, the authors hypothesized that the pharmacologic inhibition of poly(adenosine diphosphate-ribose) polymerase by PJ-34 would attenuate ventilator-induced lung injury.
Anesthetized rats were subjected to intratracheal instillation of lipopolysaccharide at a dose of 6 mg/kg. The animals were then randomly assigned to receive mechanical ventilation at either low tidal volume (6 ml/kg) with 5 cm H2O positive end-expiratory pressure or high tidal volume (15 ml/kg) with zero positive end-expiratory pressure, in the presence and absence of intravenous administration of PJ-34.
The high-tidal-volume ventilation resulted in an increase in poly(adenosine diphosphate-ribose) polymerase activity in the lung. The treatment with PJ-34 maintained a greater oxygenation and a lower airway plateau pressure than the vehicle control group. This was associated with a decreased level of interleukin 6, active plasminogen activator inhibitor 1 in the lung, attenuated leukocyte lung transmigration, and reduced pulmonary edema and apoptosis. The administration of PJ-34 also decreased the systemic levels of tumor necrosis factor alpha and interleukin 6, and attenuated the degree of apoptosis in the kidney.
The pharmacologic inhibition of poly(adenosine diphosphate-ribose) polymerase reduces ventilator-induced lung injury and protects kidney function.
Immune checkpoint inhibitor therapies targeting PD‐1/PD‐L1 are now the standard of care in oncology across several hematologic and solid tumor types, including triple negative breast cancer (TNBC). ...Patients with metastatic or locally advanced TNBC with PD‐L1 expression on immune cells occupying ≥1% of tumor area demonstrated survival benefit with the addition of atezolizumab to nab‐paclitaxel. However, concerns regarding variability between immunohistochemical PD‐L1 assay performance and inter‐reader reproducibility have been raised. High tumor‐infiltrating lymphocytes (TILs) have also been associated with response to PD‐1/PD‐L1 inhibitors in patients with breast cancer (BC). TILs can be easily assessed on hematoxylin and eosin–stained slides and have shown reliable inter‐reader reproducibility. As an established prognostic factor in early stage TNBC, TILs are soon anticipated to be reported in daily practice in many pathology laboratories worldwide. Because TILs and PD‐L1 are parts of an immunological spectrum in BC, we propose the systematic implementation of combined PD‐L1 and TIL analyses as a more comprehensive immuno‐oncological biomarker for patient selection for PD‐1/PD‐L1 inhibition‐based therapy in patients with BC. Although practical and regulatory considerations differ by jurisdiction, the pathology community has the responsibility to patients to implement assays that lead to optimal patient selection. We propose herewith a risk‐management framework that may help mitigate the risks of suboptimal patient selection for immuno‐therapeutic approaches in clinical trials and daily practice based on combined TILs/PD‐L1 assessment in BC.
The interstitial cells of Cajal have been identified in locations beyond the gastrointestinal tract, including the prostate, uterus and bladder. Indeed, there are reports of primary gastrointestinal ...stromal tumor (GIST) arising from each of these sites. We report the case of a 72-year old male who presented with benign prostatic hypertrophy and was diagnosed on retropubic prostatectomy as having a GIST. While the initial clinical and radiologic impression was that of a primary prostatic GIST, subsequent imaging ultimately revealed a small rectal extension as the source of the lesion. The purpose of our report is to highlight the need to assiduously rule-out gastrointestinal sources of GIST prior to making the diagnosis of primary prostatic GIST.
We evaluated the lineage specificity of CD79a in acute leukemias using 3-color flow cytometry in 58 consecutive cases. A panel of cell-surface antigens, including myeloid-associated markers, ...B-cell-associated markers, and T-cell-associated markers, was used. All cases of acute myeloid leukemia were CD79a-, whereas all cases of B-lineage acute lymphoblastic leukemia (ALL) were CD79a+. Three of 8 cases of T-cell ALL showed variable CD79a expression, indicating the presence of a blast subset expressing a relatively high level of CD79a. We investigated the clinical and pathologic characteristics of these 3 cases. All 3 cases had L1 or L2 morphology and expressed surface CD3. None of the other B-cell-associated markers were positive, although 1 case expressed CD13 and CD33. Uncommon random karyotypic abnormalities were identified in all 3 cases. Molecular studies demonstrated monoclonal gene rearrangement of T-cell receptor gamma in 2 of 3 cases. All 3 patients were 18 years old or younger; 1 patient did not enter remission, and 1 had disease relapse in 8 months. Our findings provide further support for the existence of a subset of T-cell ALL coexpressing CD3 and CD79a. Further study of the clinical and biologic significance of this subset may be warranted.
We report the case of a 62-year-old man with headache and left sixth cranial nerve palsy. A computerized tomography scan revealed an osteolytic process involving the sella turcica and clivus. A ...partial tumor resection was achieved via an endoscopic transsphenoidal approach. Morphologic investigation revealed a diffuse large B cell lymphoma involving pituitary parenchyma. No systemic disease was found upon staging. Primary pituitary lymphoma is extremely rare. An accurate histologic diagnosis is key to successful treatment and a favorable prognosis. The literature is reviewed.
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