Frequencies of 4 tumor-infiltrating lymphocytes potently predict survival in glioblastoma, an immune desert.

BACKGROUND: GBM is an aggressive grade 4 primary brain tumor (BT), with a 5%-13% 5-year survival. Most human GBMs manifest as immunologically "cold" tumors or "immune deserts," yet the promoting or suppressive roles of specific lymphocytes within the GBM tumor microenvironment (TME) is of considerable debate. METHODS: We used meticulous multiparametric flow cytometry (FC) to determine the lymphocytic frequencies in 102 GBMs, lower-grade gliomas, brain metastases, and nontumorous brain specimen. FC-attained frequencies were compared with frequencies estimated by "digital cytometry." The FC-derived data were combined with the patients' demographic, clinical, molecular, histopathological, radiological, and survival data. RESULTS: Comparison of FC-derived data to CIBERSORT-estimated data revealed the poor capacity of digital cytometry to estimate cell frequencies below 0.2%, the frequency range of most immune cells in BTs. Isocitrate dehydrogenase (IDH) mutation status was found to affect TME composition more than the gliomas' pathological grade. Combining FC and survival data disclosed that unlike other cancer types, the frequency of helper T cells (Th) and cytotoxic T lymphocytes (CTL) correlated negatively with glioma survival. In contrast, the frequencies of γδ-T cells and CD56bright natural killer cells correlated positively with survival. A composite parameter combining the frequencies of these 4 tumoral lymphocytes separated the survival curves of GBM patients with a median difference of 10 months (FC-derived data; P < .0001, discovery cohort), or 4.1 months (CIBERSORT-estimated data; P = .01, validation cohort). CONCLUSIONS: The frequencies of 4 TME lymphocytes strongly correlate with the survival of patients with GBM, a tumor considered an immune desert.

Sialendoscopy enhances saliva production of parotid glands in primary Sjögren syndrome patients.

OBJECTIVE: Primary Sjögren syndrome (pSS) is a chronic systemic autoimmune disorder that harms exocrine glands located mainly in the oral and ocular regions. pSS patients often complain about pain and mouth dryness. The aim of this retrospective study was to evaluate the influence of parotid glands' sialendoscopy on salivary flow in pSS patients and to assess the tissue characteristics of the parotid glands during the sialendoscopy procedure. METHOD AND MATERIALS: Twenty-six pSS patients (52 glands) treated with sialendoscopy for their parotid glands between the years 2017 and 2019 were included. The unstimulated whole saliva (UWS) flow rate was obtained 2 weeks before intervention (T1) and 3 months post intervention (T2). For 20 patients, UWS was measured 6 months post intervention (T3); and for 11 patients, UWS was measured 12 months post intervention (T4). Patients were asked about their oral quality of life before and after sialendoscopy. RESULTS: UWS was significantly higher at T2, T3, and T4 compared to T1 (P = .002, P = .01, and P = .04 respectively). In total, 22 patients (84.6%) reported substantial improvement of their oral quality of life at T2. Of the 52 glands, 33 (63.5%) exhibited avascularity in the walls of the Stensen duct, 33 (63.5%) had strictures, and in 8 (15.4%) mucus plugs were present. No major complications were observed in this study except for one patient who suffered from duct perforation, which during follow-up was spontaneously healed. CONCLUSION: This study indicates a positive effect of sialendoscopy on salivary flow rate and oral quality of life in pSS patients. Sialendoscopy should be considered as a vital tool in treating pSS patients. (Quintessence Int 2023;54:234-240; doi: 10.3290/j.qi.b3609681).

Pregnancy outcome after in utero exposure to local anesthetics as part of dental treatment: A prospective comparative cohort study.

BACKGROUND: Dental treatment and use of local anesthetics during pregnancy generally are considered harmless because of lack of evidence of adverse pregnancy effects. Data on the safety of dental treatment and local anesthetics during pregnancy are scant. Dental care is often a reason for concern both among women and their health care providers. The primary objective of this study was to evaluate the rate of major anomalies after exposure to local anesthetics as part of dental care during pregnancy. METHODS: The authors performed a prospective, comparative observational study at the Israeli Teratology Information Services between 1999 and 2005. RESULTS: The authors followed 210 pregnancies exposed to dental local anesthetics (112 [53%] in the first trimester) and compared them with 794 pregnancies not exposed to teratogens. The rate of major anomalies was not significantly different between the groups (4.8% versus 3.3%, P = .300). There was no difference in the rate of miscarriages, gestational age at delivery, or birth weight. The most common types of dental treatment were endodontic treatment (43%), tooth extraction (31%), and tooth restoration (21%). Most women (63%) were not exposed to additional medications. Approximately one-half (51%) of the women were not exposed to dental radiography, and 44% were exposed to radiation, mostly bite-wing radiography. CONCLUSIONS: This study's results suggest that use of dental local anesthetics, as well as dental treatment during pregnancy, do not represent a major teratogenic risk. PRACTICAL IMPLICATIONS: There seems to be no reason to prevent pregnant women from receiving dental treatment and local anesthetics during pregnancy.