Risk factors associated with late-onset hearing loss in children with congenital cytomegalovirus: a systematic review.

PURPOSE: To search for existing evidence of prognostic factors related to the development of late-onset hearing loss (LOHL) in infants with congenital cytomegalovirus (cCMV). METHODS: A PRISMA systematic review was performed, with the PubMed, Embase, and Web of Science databases searched from inception through to December 2023; after the application of inclusion and exclusion criteria a total of 9 papers were included in this review. PROSPERO registration number CRD42024492244. RESULTS: 9 studies encompassing a total of 292 children with late-onset hearing loss were included. A total of 12 risk factors were identified in the literature, with 6 found to be statistically significant. Late-onset hearing loss was more frequently reported in children with symptomatic than asymptomatic cCMV. Moreover, in asymptomatic cCMV cases, elevated DNAemia and salivary viral load were associated with late-onset hearing loss. Additionally, first-trimester seroconversion was identified as a risk factor for late- onset hearing loss. Further, gestational age < 37 weeks and low birth weight were found to correlate with late-onset hearing loss. Remarkably, only one study documented a relationship between late-onset hearing loss and ultrasonographic abnormalities. CONCLUSIONS: Although six statistically significant risk factors have been identified, the available evidence is limited and inconsistent, preventing the establishment of reliable neonatal and maternal parameters to predict the development of LOHL in patients with CMV. There are few studies addressing this topic, and those available exhibit a low level of evidence and heterogeneous designs. More studies should be done.

Prognosticators of Excision of Giant Intra-Oral Tumors in a Resource-Challenged Setting: A Case Report.

Minor salivary glands are widely distributed in the mucosal surface of the lips, palate, nasal cavity, pharynx, and larynx, thus can arise from any of these primary sites. Intra-oral minor salivary gland tumors (IMSGTs), while considered rare in the general population are relatively more common when compared to all the other extra-oral sites. Pleomorphic adenoma, as seen in the index patient, is the most commonly diagnosed benign IMSGT. Intra-oral minor salivary gland tumors are not uncommon and depending on their size, nature, and location can be associated with severe limitation of the Patient's ability to breathe, speak clearly, and/or swallow and consequent severe morbidity and even mortality. In addition to these deleterious effects, they present a major surgical challenge to the surgeon, who has to determine the safest, most feasible access to ensure complete, or near-complete excision, as well as to the anesthetist, who needs to secure a definitive airway through the nose or mouth, both of which could be significantly restricted by the presence of the tumor. The aim is to present our successful management of one of the largest intra-oral minor salivary gland tumors documented in the literature, highlighting the specific measures we undertook to tackle the peculiar surgical and anesthetic challenges we faced. It had been two years since surgery and the patient is thriving with a markedly improved quality of life and no features of recurrence. The patient is a 50-year-old male with a slowly growing painless, left palatal mass in the roof of the mouth of 10 years duration with recurrent spontaneous bloody discharge effluent and snoring. There was an associated history of dysphagia to solid with associated choking spells, a left-sided facial asymmetry with no cheek swelling, odynophagia, sore throat, or difficulty with breathing. There was ipsilateral loss of upper incisors and dental anarchy about two years before presentation. No other nasal, otologic, or ophthalmic symptoms were present. No neck swelling, stiffness, cough, or chest symptoms. The oropharyngeal physical examination was highly restricted due to the intra-oral size of the mass. Figure 1. There was facial asymmetry with a bulge of the left maxilla, left-sided levels 1b and 2 non-tender lymph node enlargements, freely mobile, not adhered to the skin. A craniofacial CT scan revealed extensive isodense heterogeneously enhancing intra-oral soft tissue mass occupying the entire palate/oral cavity and encroaching laterally on the masticator and the parapharyngeal space with erosion of the left maxillary floor and hyoid bone Figure 2. The patient had an excision biopsy of the palatal mass with a free margin. No frozen section at the time of surgery. Histology revealed Pleomorphic adenoma and was followed up for 2 years with no evidence of recurrence. Prognosticators are delay in presentation leading to an increase in size of the mass and severe limitation of the patient's ability to breathe, speak clearly, and/or swallow and consequent severe morbidity and even mortality, the surgeon not being overwhelmed, the skillful Anaesthesist that could maneuver the nasal cavity without us doing tracheostomy and the successful outcome of the surgery.

Les glandes salivaires mineures sont largement réparties à la surface muqueuse des lèvres, du palais, de la cavité nasale, du pharynx et du larynx, et peuvent donc survenir à partir de l'un de ces sites primaires. Les tumeurs des glandes salivaires mineures intra-orales (TGSMIO), bien que considérées comme rares dans la population générale, sont relativement plus courantes par rapport à tous les autres sites extra-oraux. L'adénome pléomorphe, tel que celui observé chez le patient index, est la TGSMIO bénigne la plus fréquemment diagnostiquée. Les tumeurs des glandes salivaires mineures intra-orales ne sont pas rares et, en fonction de leur taille, de leur nature et de leur emplacement, peuvent être associées à une limitation sévère de la capacité du patient à respirer, à parler clairement et/ou à avaler, avec une morbidité sévère et même une mortalité. Outre ces effets délétères, elles présentent un défi chirurgical majeur pour le chirurgien, qui doit déterminer l'accès le plus sûr et le plus faisable pour assurer une excision complète ou presque complète, ainsi que pour l'anesthésiste, qui doit assurer une voie aérienne définitive par le nez ou la bouche, tous deux pouvant être significativement restreints par la présence de la tumeur. L'objectif est de présenter notre prise en charge réussie de l'une des plus grandes TGSMIO documentées dans la littérature, mettant en évidence les mesures spécifiques que nous avons prises pour relever les défis chirurgicaux et anesthésiques particuliers auxquels nous avons été confrontés. Deux ans après l'intervention, le patient se porte bien avec une nette amélioration de sa qualité de vie et aucune manifestation de récurrence. Le patient est un homme de 50 ans présentant une masse palatine gauche en croissance lente et indolore dans le palais depuis 10 ans, avec des écoulements sanguins spontanés récurrents et des ronflements. Il y avait une histoire associée de dysphagie aux solides avec des épisodes d'étouffement, une asymétrie faciale du côté gauche sans tuméfaction de la joue, une odynophagie, un mal de gorge ou des difficultés respiratoires. Il y avait une perte ipsilatérale des incisives supérieures et une anarchie entaire environ deux ans avant la présentation. Aucun autre symptôme nasal, otologique, ophtalmique n'était présent. Aucun gonflement du cou, raideur, toux ou symptômes thoraciques. L'examen physique de l'oropharynx était fortement limité en raison de la taille intra-orale de la masse. Figure 1. Il y avait une asymétrie faciale avec une bosse du maxillaire gauche, des ganglions lymphatiques non douloureux des niveaux 1b et 2 du côté gauche, mobiles librement, non adhérents à la peau. La tomodensitométrie craniofaciale a révélé une masse tissulaire molle intraorale extensive, hétérogène, rehaussée de manière isodense occupant l'ensemble du palais/cavité buccale et empiétant latéralement sur les muscles masticateurs et l'espace parapharyngé, avec érosion du plancher du maxillaire gauche et de l'os hyoïde. Figure 2. Le patient a subi une biopsie d'excision de la masse palatine avec une marge libre. Aucune section congelée n'a été réalisée lors de la chirurgie. L'histologie a révélé un adénome pléomorphe et un suivi de 2 ans n'a montré aucun signe de récurrence. Les facteurs pronostiques comprennent le retard de la présentation entraînant une augmentation de la taille de la masse et une limitation sévère de la capacité du patient à respirer, à parler clairement et/ou à avaler, avec une morbidité sévère voire une mortalité, le chirurgien ne se laissant pas dépasser, l'anesthésiste compétent pouvant manœuvrer dans la cavité nasale sans avoir recours à une trachéotomie, et le succès de l'intervention chirurgicale. MOTS-CLÉS: Intraoral; Glande salivaire mineure; Excision; Tumeur; Pronostiqueurs.

Multi-institutional search for patient factors associated with adverse events following tracheotomy.

BACKGROUND: Tracheotomy is a common procedure for otolaryngologists. The risk of complications is difficult to predict. This study aims to identify measurable preoperative indicators associated with adverse events following tracheotomy. METHODS: The charts of adults undergoing tracheotomy for respiratory failure at one of four university-affiliated hospitals between 1/2012 and 8/2018 were reviewed. Complications were analyzed in the context of demographics, physiologic parameters, and comorbidities. RESULTS: Among 507 tracheotomies performed, the most common complications included infection, bleeding, and cardiac arrest. Mortality was 39 % in patients with pulmonary hypertension, 42 % in those with ejection fraction ≤ 40 and 32 % in those with abnormal right ventricular function, double the rates in patients without each of these findings. CONCLUSION: Many critically ill tracheotomy patients experience significant rates of adverse events. Risk factors for mortality include ejection fraction ≤ 40, pulmonary hypertension, and abnormal ventricular function. These should be considered for use in preoperative counseling.

Mucoepidermoid carcinoma of the head and neck: CRTC1/3 MAML 2 translocation and its prognosticators.

PURPOSE: Mucoepidermoid carcinoma (MEC) of the head and neck is a prevalent malignant salivary gland tumour with a reported good outcome. The aim of this study was to report the outcome in our centre. METHODS: A retrospective chart analysis with survival analyses was performed combined with fluorescence in situ hybridization (FISH) analysis to assess CRTC1/3 MAML 2 fusion gene presence. RESULTS: Sixty-four cases of MEC were identified. Median age at presentation was 51.4 years with a predominance for parotid gland involvement. Five, 10- and 20- year disease-free survival was 98%, 90% and 68%, respectively. Overall survival was 94%, 90% and 64%, respectively. Local recurrence was seen up to 14 years after primary diagnosis; distant metastases were diagnosed up to 17 years later. The overall recurrence rate was less than 20 per cent. CRTC1/3 MAML 2 fusion gene presence showed no survival benefit. CONCLUSION: MEC of the head and neck has a favorable outcome with the exception of high-grade MEC. PNI and nodal involvement are not rare. CRTC1/3 MAML 2 fusion gene presence showed no survival benefit. The tendency for late onset of loco-regional and distant recurrence should not be underestimated.

P-Cadherin and WNT5A expression in assessment of lymph node metastasis in oral squamous cell carcinoma.

BACKGROUND: Oral cancer progression is a multi-step process in which adhesion molecules play a pivotal role in the development of recurrent, invasive, and distant metastasis. The aim of this study was to adopt prognostic biomarkers to assess the lymph node metastasis of OSCC that will facilitate in deciding the treatment modality by the surgeons. OBJECTIVES: The objectives of the study were to assess the biological behaviour of OSCC by correlating the expression levels of P-Cadherin and WNT5A immunohistochemically. METHODS: A total of 60 selected OSCCs cases (lymph node metastasis n = 30, non-metastatic n = 30) and 10 normal healthy controls were quantitatively and qualitatively analysed by immunohistochemistry for P-Cadherin and WNT5A. A survival analysis was also performed. RESULTS: The expression levels of P-Cadherin and WNT5A in OSCC groups were statistically significant between metastatic and non-metastatic groups (p < 0.001). P-Cadherin and WNT5A expression in metastatic (lymph node metastasis) and non-metastatic cases showed a significant correlation coefficient of 0.753 at (p < 0.01). The present study also found that the aberrant expression (high) of P-Cadherin was associated with diminished survival of patients with metastatic OSCC. CONCLUSION: The present study demonstrated the aberrant expression of P-Cadherin and WNT5A could serve as important prognosticator in OSCC. CLINICAL RELEVANCE: P-Cadherin and WNT5A could be used as significant predictors of disease outcome.

Salvage surgery in head and neck cancer.

Salvage surgery after failed organ preservation treatment offers challenges for both the patient and the surgeon. The outcome is often uncertain and even today, 5-year overall survival does not exceed 50 per cent. The chemoradiotherapy induced toxicity asks for meticulous discussion and planning in a multidisciplinary manner in a changing environment of increasing incidence of human papillomavirus induced oropharyngeal tumours, evolving surgical techniques and patient participation. Herein, we discuss the latest literature on salvage surgery and the need for identifying the proper prognosticators to ensure for an optimal treatment plan in potentially salvageable patients.

A conceptual time window-based model for the early stratification of trauma patients.

Progress in the testing of therapies targeting the immune response following trauma, a leading cause of morbidity and mortality worldwide, has been slow. We propose that the design of interventional trials in trauma would benefit from a scheme or platform that could support the identification and implementation of prognostic strategies for patient stratification. Here, we propose a stratification scheme based on defined time periods or windows following the traumatic event. This 'time-window' model allows for the incorporation of prognostic variables ranging from circulating biomarkers and clinical data to patient-specific information such as gene variants to predict adverse short- or long-term outcomes. A number of circulating biomarkers, including cell injury markers and damage-associated molecular patterns (DAMPs), and inflammatory mediators have been shown to correlate with adverse outcomes after trauma. Likewise, several single nucleotide polymorphisms (SNPs) associate with complications or death in trauma patients. This review summarizes the status of our understanding of the prognostic value of these classes of variables in predicting outcomes in trauma patients. Strategies for the incorporation of these prognostic variables into schemes designed to stratify trauma patients, such as our time-window model, are also discussed.

Unbiased data mining identifies cell cycle transcripts that predict non-indolent Gleason score 7 prostate cancer.

BACKGROUND: Patients with newly diagnosed non-metastatic prostate adenocarcinoma are typically classified as at low, intermediate, or high risk of disease progression using blood prostate-specific antigen concentration, tumour T category, and tumour pathological Gleason score. Classification is used to both predict clinical outcome and to inform initial management. However, significant heterogeneity is observed in outcome, particularly within the intermediate risk group, and there is an urgent need for additional markers to more accurately hone risk prediction. Recently developed web-based visualization and analysis tools have facilitated rapid interrogation of large transcriptome datasets, and querying broadly across multiple large datasets should identify predictors that are widely applicable. METHODS: We used camcAPP, cBioPortal, CRN, and NIH NCI GDC Data Portal to data mine publicly available large prostate cancer datasets. A test set of biomarkers was developed by identifying transcripts that had: 1) altered abundance in prostate cancer, 2) altered expression in patients with Gleason score 7 tumours and biochemical recurrence, 3) correlation of expression with time until biochemical recurrence across three datasets (Cambridge, Stockholm, MSKCC). Transcripts that met these criteria were then examined in a validation dataset (TCGA-PRAD) using univariate and multivariable models to predict biochemical recurrence in patients with Gleason score 7 tumours. RESULTS: Twenty transcripts met the test criteria, and 12 were validated in TCGA-PRAD Gleason score 7 patients. Ten of these transcripts remained prognostic in Gleason score 3 + 4 = 7, a sub-group of Gleason score 7 patients typically considered at a lower risk for poor outcome and often not targeted for aggressive management. All transcripts positively associated with recurrence encode or regulate mitosis and cell cycle-related proteins. The top performer was BUB1, one of four key MIR145-3P microRNA targets upregulated in hormone-sensitive as well as castration-resistant PCa. SRD5A2 converts testosterone to its more active form and was negatively associated with biochemical recurrence. CONCLUSIONS: Unbiased mining of large patient datasets identified 12 transcripts that independently predicted disease recurrence risk in Gleason score 7 prostate cancer. The mitosis and cell cycle proteins identified are also implicated in progression to castration-resistant prostate cancer, revealing a pivotal role for loss of cell cycle control in the latter.

Early Prediction of Therapy Response to Abiraterone Acetate Using PSA Subforms in Patients with Castration Resistant Prostate Cancer.

The purpose of this study was to evaluate the prognostic ability of early changes of total prostate specific antigen (tPSA), free PSA (fPSA), [-2]proPSA and the Prostate Health Index (PHI) following initiation of Abiraterone-therapy in men with castration resistant prostate cancer (mCRPC). In 25 patients, PSA-subforms were analyzed before and at 8-12 weeks under therapy as prognosticators of progression-free-survival (PFS) and overall survival (OS). Comparing patients with a PFS < vs. ≥12 months by using Mann-Whitney-Wilcoxon Tests, the relative-median-change of tPSA (-0.1% vs. -86.8%; p = 0.02), fPSA (12.1% vs. -55.3%; p = 0.03) and [-2]proPSA (8.1% vs. -59.3%; p = 0.05) differed significantly. For men with ≤ vs. >15 months of OS there was a non-significant trend for a difference in the relative-median-change of fPSA (17.0% vs. -46.3%; p = 0.06). In Kaplan-Meier analyses, declining fPSA and [-2]proPSA were associated with a longer median PFS (13 months, 95% confidence interval (CI): 9.6-16.4 vs. 10 months, 95% CI: 3.5-16.5; p = 0.11), respectively. Correspondingly, decreasing fPSA and [-2]proPSA values indicated an OS of 32 months (95% CI: not reached (NR)) compared to 21 months in men with rising values (95% CI: 7.7-34.3; p = 0.14), respectively. We concluded that the addition of fPSA- and [-2]proPSA-changes to tPSA-information might be further studied as potential markers of early Abiraterone response in mCRPC patients.

Prognostic factors in solitary fibrous tumors of the pleura.

BACKGROUND: Solitary fibrous tumors of the pleura (SFTP) are rare neoplasms originating from submesothelial mesenchymal cells with fibroblastic differentiation. The clinical behavior of SFTPs is mostly benign; however, up to 20% of patients develop local recurrence and/or distant metastasis. Although different risk-stratification models have been described, definitive criteria to predict a malignant clinical course of SFTP are still lacking. METHODS: In a retrospective analysis at a single-institution, 25 patients with histologically proven SFTP were identified. Clinicopathologic and survival data were collected and pathologic sections reviewed. Different markers and risk-stratification models were correlated with disease- and overall-free survival by Kaplan-Meier analysis. RESULTS: Of 25 SFTP, 8 tumors (32%) were classified as malignant according to the World Health Organization criteria. Three patients (12%) developed recurrence. Cohort median follow-up was 28 mo, and median overall survival was 160 mo. Comparison of proliferation markers showed higher mitosis count per high-power field and MIB-1 labeling index (MIB) in malignant compared with nonmalignant SFTP. MIB was identified as a predictor for disease-free survival. Applying the previously reported classifications to categorize SFTP according to the probability to show malignant behavior, significant differences in disease-free survival were also present in our cohort. CONCLUSIONS: In the present analysis of rare SFTP, previously proposed staging systems were applicable for prediction of disease-free survival. Independently of treatment, MIB was the only sole predictive marker. A prospective multi-institutional database could be helpful in establishing detailed predictive criteria in patients diagnosed with SFTP.

Prognostication in chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in Western countries. CLL is a highly heterogeneous disease: some patients may never require therapy and others relapse several times after different therapeutic strategies. Therefore, in CLL, prognostic markers are essential to capture high-risk patients for different clinical endpoints including early treatment requirement, early progression after BTK or BCL2 inhibitors and Richter transformation. In early stage CLL, different biological and clinical biomarkers have been identified to predict time to treatment requirement that could be used to identify the most appropriate population for early intervention clinical trial. However, at the moment, the standard of care for early stage CLL remains watch & wait since no survival benefit has been identified in clinical trials with chemoimmunotherapy and with BTK inhibitors. In patients requiring treatment TP53 disruptions identify high-risk patients who benefit the most from long-term continuous therapy with BTKi. On the opposite side of the spectrum, IGHV mutated patients devoid of TP53 disruption benefit the most from fixed-duration therapy with venetoclax-obinutuzumab. In between, the highly heterogenous subgroup of patients with IGHV unmutated genes represents the group in which further efforts are needed to identify additional prognostic biomarkers aimed at selecting patients who can benefit from fixed-duration and patients who can benefit from long term BTKi therapy. In the context of the aggressive transformation of CLL, namely Richter syndrome, the clonal relationship to the CLL counterpart represents the strongest prognostic biomarker. Clonally related Richter syndrome still represents an unmet clinical need which requires further efforts to identify new therapeutic strategies.

Clinical prognosticators and targets in the immune microenvironment of intrahepatic cholangiocarcinoma.

Background: Intrahepatic cholangiocarcinoma (ICC) is a disease with poor prognosis and limited therapeutic options. We investigated the tumor immune microenvironment (TIME) to identify predictors of disease outcome and to explore targets for therapeutic modulation. Methods: Liver tissue samples were collected during 2008-2019 from patients (n = 139) diagnosed with ICC who underwent curative intent surgery without neoadjuvant chemotherapy. Samples from the discovery cohort (n = 86) were immunohistochemically analyzed on tissue microarrays (TMAs) for the expression of CD68, CD3, CD4, CD8, Foxp3, PD-L1, STAT1, and p-STAT1 in tumor core and stroma areas. Results were digitally analyzed using QuPath software and correlated with clinicopathological characteristics. For validation of TIME-related biomarkers, we performed multiplex imaging mass cytometry (IMC) in a validation cohort (n = 53). Results: CD68+ cells were the predominant immune cell type in the TIME of ICC. CD4+high T cell density correlated with better overall survival (OS). Prediction modeling together with validation cohort confirmed relevance of CD4+ cells, PD-L1 expression by immune cells in the stroma and N-stage on overall disease outcome. In turn, IMC analyses revealed that silent CD3+CD4+ clusters inversely impacted survival. Among annotated immune cell clusters, PD-L1 was most relevantly expressed by CD4+FoxP3+ cells. A subset of tumors with high density of immune cells ("hot" cluster) correlated with PD-L1 expression and could identify a group of candidates for immune checkpoint inhibition (ICI). Ultimately, higher levels of STAT1 expression were associated with higher lymphocyte infiltration and PD-L1 expression. Conclusions: These results highlight the importance of CD4+ T cells in immune response against ICC. Secondly, a subset of tumors with "hot" TIME represents potential candidates for ICI, while stimulation of STAT1 pathway could be a potential target to turn "cold" into "hot" TIME in ICC.

The tumor immune microenvironment (TIME) plays a critical role in the immune response In many cancers, including intrahepatic cholangiocarcinoma (ICC). Molecular subtyping of the ICC microenvironment already revealed inter-tumoral heterogeneity with variant profiles of immune cell infiltrates. A recent study created an in-depth immune cell atlas of the TIME in biliary tract cancers and could demonstrate the relevance of specific immune cell subpopulations on patient outcome. We are able to provide a distinctive characterization of TIME, separating tumor epithelial- and stroma areas, in a large and representative ICC cohort using digitalized image analysis on tissue microarrays (TMA) as well as multiplex imaging mass cytometry (IMC). The study was designed for identification of immune cell prognosticators allocating institutional ICC patients into a discovery (2008­15) and a validation (2010­19) cohort. Immune cell subpopulations were correlated with clinicopathological characteristics and patient outcome. Our results highlight: i. The important role of CD4+ T cell infiltration in ICC patients; ii. ICC tumors with high density of immune cells associated with PD-L1 expression identifies a subset of patients with variant tumor biology; iii. Stimulation of STAT1 pathway may be a relevant target to turn "cold" into "hot" tumors.

Literature review and expert opinion on the treatment of high-risk acute myeloid leukemia in patients who are eligible for intensive chemotherapy.

In patients with Acute Myeloid Leukemia (AML), the assessment of disease risk plays a central role in the era of personalized medicine. Indeed, integrating baseline clinical and biological features on a case-by-case basis is not only essential to select which treatment would likely result in a higher probability of achieving complete remission, but also to dynamically customize any subsequent therapeutic intervention. For young high-risk patients with low comorbidities burden and in good general conditions (also called "fit" patients), intensive chemotherapy followed by allogeneic stem cell transplantation still represents the backbone of any therapeutic program. However, with the approval of novel promising agents in both the induction/consolidation and the maintenance setting, the algorithms for the management of AML patients considered eligible for intensive chemotherapy are in constant evolution. In this view, we selected burning issues regarding the identification and management of high-risk AML, aiming to provide practical advice to facilitate their daily clinical management in patients considered eligible for intensive chemotherapy.

Prognostic Values of Systemic Inflammatory Immunological Markers in Glioblastoma: A Systematic Review and Meta-Analysis.

BACKGROUND: Neutrophils are an important part of the tumor microenvironment, which stimulates inflammatory processes through phagocytosis, degranulation, release of small DNA fragments (cell-free DNA), and presentation of antigens. Since neutrophils accumulate in peripheral blood in patients with advanced-stage cancer, a high neutrophil-to-lymphocyte ratio can be a biomarker of a poor prognosis in patients with glioblastoma. The present study aimed to explore the prognostic value of the preoperative levels of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune inflammation index (SII), systemic inflammation response index (SIRI), and cell-free DNA (cfDNA) to better predict prognostic implications in the survival rate of glioblastoma patients. METHODS: The meta-analysis was carried out according to the recommendations and standards established by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Databases of PubMed, EBSCO, and Medline were systematically searched to select all the relevant studies published up to December 2022. RESULTS: Poorer prognoses were recorded in patients with a high NLR or PLR when compared with the patients with a low NLR or PLR (HR 1.51, 95% CI 1.24-1.83, p < 0.0001 and HR 1.34, 95% CI 1.10-1.63, p < 0.01, respectively). Similarly, a worse prognosis was reported for patients with a higher cfDNA (HR 2.35, 95% CI 1.27-4.36, p < 0.01). The SII and SIRI values were not related to glioblastoma survival (p = 0.0533 and p = 0.482, respectively). CONCLUSIONS: Thus, NLR, PLR, and cfDNA, unlike SII and SIRI, appeared to be useful and convenient peripheral inflammatory markers to assess the prognosis in glioblastoma.

Histopathological prognosticators and their clinicopathological correlation in oral squamous cell carcinomas of the tongue.

Background: Tongue carcinomas account for 25%-40% of intraoral squamous cell carcinomas (OSCCs). Although TNM staging systems is an international standard for cancer reporting, prognosis evaluation, and treatment planning, multiple histopathological risk assessment predictors such as tumor thickness (TT), tumor shape, tumor growth pattern, and invasive malignancy grading scoring systems have been studied and should form a basis for prediction and prognostication of such aggressive carcinomas. Aim: To evaluate and characterize the histomorphological prognostic indicators in OSCCs of tongue and compare it with OSCCs of other anatomic sites within the oral cavity. Furthermore, to elucidate the significance of histopathological indicators in predicting prognosis of tongue squamous cell carcinomas (SCCs). Materials and Methods: Forty SCC cases with 20 each of tongue and 20 from other intraoral sites were retrieved from department archives. Clinical data and staging were obtained for each case. Histomorphological parameters including pattern of invasion (POI), tumor budding (TB), depth of invasion (DOI), TT, lymphocytic host response, tumor-associated tissue eosinophilia (TATE), vascular invasion, perineural invasion (PNI), and muscular invasion were assessed. The results were statistically evaluated. Results: TB, DOI, and sarcolemmal spread were significant histologic predictors in tongue SCC. Upon correlation of histomorphological parameters with clinical staging, TT, POI, and TATE were observed to be significantly correlated (P ≤ 0.05). Conclusion: The histomorphological risk assessment model may serve as important addition to the existing prognosticators and may be used as a prognostic index to help plan and individualize treatment protocol in cases with aggressive high-risk disease for whom the use of multimodality treatment seems beneficial.

Prognosticators and Prognostic Nomograms for Leiomyosarcoma Patients With Metastasis.

Individual survival prediction and risk stratification are of vital importance to optimize the individualized treatment of metastatic leiomyosarcoma (LMS) patients. This study aimed to identify the prognostic factors for metastatic LMS patients and establish prognostic models for overall survival (OS) and cancer-specific survival (CSS). The data of LMS patients with metastasis between 2010 and 2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. The entire cohort was randomly divided into a training cohort and a validation cohort. The influences of primary tumor site, localized and distant metastases, and sites and number of metastases on the prognosis of metastatic LMS patients were firstly explored by Kaplan-Meier curves and log-rank tests. Furthermore, the effective therapeutic regimens and prognosticators for metastatic LMS patients were also analyzed by Cox analysis. In addition, two prognostic nomograms for OS and CSS were established, and their predictive performances were evaluated by the methods of receiver operating characteristic (ROC) curves, time-dependent ROC curves, calibration curves, and decision curve analysis (DCA). A total of 498 patients were finally collected from the SEER database and were randomly assigned to the training set (N = 332) and validation set (N = 166). No significant differences in OS were observed in patients with distant organ metastasis and localized metastasis. For patients who have already developed distant organ metastasis, the sites and number of metastases seemed to be not closely associated with survival. Patients who received chemotherapy got significantly longer survival than that of their counterparts. In univariate and multivariate Cox analyses, variables of surgery, chemotherapy, age, and tumor size were identified as independent predictors for OS and CSS, and distant metastasis was also independently associated with CSS. The areas under the curve (AUCs) of ROC curves of the nomogram for predicting 1-, 3-, and 5-year OS were 0.770, 0.800, and 0.843, respectively, and those for CSS were 0.777, 0.758, and 0.761, respectively. The AUCs of time-dependent AUCs were all over 0.750. The calibration curves and DCA curves also showed excellent performance of the prognostic nomograms. Metastasis is associated with reduced survival, while the sites and the number of metastases are not significantly associated with survival. The established nomogram is a useful tool that can help to perform survival stratification and to optimize prognosis-based decision-making in clinical practice.

Clinical factors associated with outcome in solid tumor patients treated with immune-checkpoint inhibitors: a single institution retrospective analysis.

OBJECTIVES: Response to immune checkpoint inhibitor (ICI) remains limited to a subset of patients and predictive biomarkers of response remains an unmet need, limiting our ability to provide precision medicine. Using real-world data, we aimed to identify potential clinical prognosticators of ICI response in solid tumor patients. METHODS: We conducted a retrospective analysis of all solid tumor patients treated with ICIs at the Mount Sinai Hospital between January 2011 and April 2017. Predictors assessed included demographics, performance status, co-morbidities, family history of cancer, smoking status, cancer type, metastatic pattern, and type of ICI. Outcomes evaluated include progression free survival (PFS), overall survival (OS), overall response rate (ORR) and disease control rate (DCR). Univariable and multivariable Cox proportional hazard models were constructed to test the association of predictors with outcomes. RESULTS: We identified 297 ICI-treated patients with diagnosis of non-small cell lung cancer (N = 81, 27.3%), melanoma (N = 73, 24.6%), hepatocellular carcinoma (N = 51, 17.2%), urothelial carcinoma (N = 51, 17.2%), head and neck squamous cell carcinoma (N = 23, 7.7%), and renal cell carcinoma (N = 18, 6.1%). In multivariable analysis, good performance status of ECOG ≤ 2 (PFS, ORR, DCR and OS) and family history of cancer (ORR and DCR) associated with improved ICI response. Bone metastasis was associated with worse outcomes (PFS, ORR, and DCR). CONCLUSIONS: Mechanisms underlying the clinical predictors of response observed in this real-world analysis, such as genetic variants and bone metastasis-tumor microenvironment, warrant further exploration in larger studies incorporating translational endpoints. Consistently positive clinical correlates may help inform patient stratification when considering ICI therapy.

Prognostic Association between Common Laboratory Tests and Overall Survival in Elderly Men with De Novo Metastatic Castration Sensitive Prostate Cancer: A Population-Based Study in Canada.

De novo cases of metastatic prostate cancer (mCSPC) are associated with poorer prognosis. To assist in clinical decision-making, we aimed to determine the prognostic utility of commonly available laboratory-based markers with overall survival (OS). In a retrospective population-based study, a cohort of 3556 men aged ≥66 years diagnosed with de novo mCSPC between 2014 and 2019 was identified in Ontario (Canada) administrative database. OS was assessed by using the Kaplan-Meier method. Multivariate Cox regression analysis was performed to evaluate the association between laboratory markers and OS adjusting for patient and disease characteristics. Laboratory markers that were assessed include neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), albumin, hemoglobin, serum testosterone and PSA kinetics. Among the 3556 older men with de novo mCSPC, their median age was 77 years (IQR: 71-83). The median survival was 18 months (IQR: 10-31). In multivariate analysis, a statistically significant association with OS was observed with all the markers (NLR, PLR, albumin, hemoglobin, PSA decrease, reaching PSA nadir and a 50% PSA decline), except for testosterone levels. Our findings support the use of markers of systemic inflammation (NLR, PLR and albumin), hemoglobin and PSA metrics as prognostic indicators for OS in de novo mCSPC.

Epidemiological characteristics and outcomes from 187 patients with COVID-19 admitted to 6 reference centers in Greece: an observational study during the first wave of the COVID-19 pandemic.

INTRODUCTION: Epidemiological data from patients with COVID-19 has been recently published in several countries. Nationwide data of hospitalized patients with COVID-19 in Greece remain scarce. MATERIAL AND METHODS: This was an observational, retrospective study from 6 reference centers between February 26 and May 15, 2020. RESULTS: The patients were mostly males (65.7%) and never smokers (57.2%) of median age 60 (95% CI: 57.6-64) years. The majority of the subjects (98%) were treated with the standard-of-care therapeutic regimen at that time, including hydroxychlo-roquine and azithromycin. Median time of hospitalization was 10 days (95% CI: 10-12). Twenty-five (13.3%) individuals were intubated and 8 died (4.2%). The patients with high neutrophil-to-lymphocyte ratio (NLR) ( > 3.58) exhibited more severe disease as indicated by significantly increased World Health Organization (WHO) R&D ordinal scale (4; 95% CI: 4-4 vs 3; 95% CI: 3-4, p = 0.0001) and MaxFiO2% (50; 95% CI: 38.2-50 vs 29.5; 95% CI: 21-31, p < 0.0001). The patients with increased lactate dehydrogenase (LDH) levels ( > 270 IU/ml) also exhibited more advanced disease compared to the low LDH group ( < 270 IU/ml) as indicated by both WHO R&D ordinal scale (4; 95% CI: 4-4 vs 4; 95% CI: 3-4, p = 0.0001) and MaxFiO2% (50; 95% CI: 35-60 vs 28; 95% CI: 21-31, p < 0.0001). CONCLUSION: We present the first epidemiological report from a low-incidence and mortality COVID-19 country. NLR and LDH may represent reliable disease prognosticators leading to timely treatment decisions.

Anatomical and Functional Recovery Kinetics After Epiretinal Membrane Removal.

PURPOSE: To investigate the nature of anatomical and functional recovery kinetics after epiretinal membrane (ERM) removal. METHODS: The records of 42 patients (45 eyes) with idiopathic ERM treated with pars plana vitrectomy and surgical peeling of the ERM performed by a single surgeon at Massachusetts Eye and Ear between 2012 and 2017 were retrospectively reviewed. Outcome measures included spectral domain optical coherence tomography-measured central macular thickness (CMT) pre-operatively and at post-operative day 1, week 1, months 1, 3, 6, 12 and 24 as well as best-corrected visual acuity (BCVA). Correlations between baseline or early values and final anatomical and functional outcomes were investigated. RESULTS: Improvement in CMT was statistically significant after 1 week, 1, 3, 6, 12 and 24 months (p < 0.01). BCVA improvement was statistically significant after 1, 6, 12 and 24 months follow-up (p<0.01). The improvement of BCVA and CMT with time was found to be logarithmic (R2 =0.96, R2 =0.84) suggesting that early (<30 days) post-operative functional and anatomical changes may be predictive of long-term outcomes. Preoperative BCVA and CMT revealed a weak positive correlation with the respective BCVA and CMT at 24 months (R2=0.13 and R2=0.16). When plotted as a percentage of the fellow normal eye CMT, first week proportional improvement in CMT from pre-operative baseline was found to be correlated with final CMT proportional decrease (R2=0.72) suggesting that first week postoperative CMT could be predictive of final CMT. CONCLUSION: There is a logarithmic improvement in CMT and BCVA after ERM peel with BCVA improvement following the CMT improvement. Early (less than 30 days) post-operative anatomical changes can be predictive of long-term anatomical outcomes.