Current and Emerging Pharmacotherapies for Primary CNS Lymphoma

Primary central nervous system lymphoma (PCNSL) constitutes a rare group of extranodal non-Hodgkin’s lymphoma (NHL) primarily of B cell origin. It occurs in both immuno-competent and immune-compromised patients. High dose m ethotrexate (HD-MTX) based chemotherapy is the standard therapy. Chemotherapy with whole brain radiation therapy (WBRT) improves response rates and survival compared with WBRT alone. However, due to the increased risk for neurotoxicity with WBRT, recent studies have focused on using chemotherapy alone. Methotrexate based multi-agent chemotherapy without WBRT is associated with similar t reatment rates and survival compared with regimens that include WBRT although controlled trials have not been performed. Because of the low incidence of this disease, it is difficult to conduct randomized controlled trials. In this article we have discussed about the past, present and emerging treatment options in patients with PCNSL

Temporomandibular disorders and fibromyalgia: A narrative review

Temporomandibular disorder (TMD) and fibromyalgia (FM) have some clinical characteristics in common, for instance the chronic evolution, the pathophysiology incompletely understood and a multifactorial genesis. The incidence and the relationship between TMD and FM patients are the aims of this review. A MEDLINE and PubMed search were performed for the key words “temporomandibular disorder” AND “fibromyalgia” from 2000 to present. A total of 19 papers were included in our review, accounting for 5449 patients. Ten studies, reporting a total of 4945 patients with TMD, showed that only 16.5% of these patients had diagnosis of FM, whereas 12 studies, reporting a total of 504 patients with FM, demonstrated that 77.0% of these patients had diagnosis of TMD. A comorbid relationship exists between TMD and FM. The complexity of both diseases shows the importance of a multimodal and interdisciplinary

Multiple brain abscesses of odontogenic origin. May oral microbiota affect their development? a review of the current literature

In the last few years, the role of oral microbiota in the setting of oral diseases such as caries, periodontal disease, oral cancer and systemic infections, including rheumatoid arthritis, car-diovascular disease and brain abscess (BA), has attracted the attention of physicians and researchers. Approximately 5–7% of all BAs have an odontogenic origin, representing an important pathological systemic condition with a high morbidity and mortality. A systematic search of two databases (Pubmed and Ovid EMBASE) was performed for studies published up to 5 January 2021, reporting multiple BAs attributed to an odontogenic origin. According to PRISMA guidelines, we included a total of 16 papers reporting multiple BAs due to odontogenic infections. The aim of this review is to investigate the treatment modality and the clinical outcome of patients with multiple BAs due to odontogenic infections, as well as to identify the most common pathogens involved in this pathological status and their role, in the oral microbiota, in the onset of oral infections. A multidisciplinary approach is essential in the management of multiple BAs. Further studies are required to understand better the role of microbiota in the development of multiple BAs

Decipher the glioblastoma microenvironment: The first milestone for new groundbreaking therapeutic strategies

Glioblastoma (GBM) is the most common primary malignant brain tumour in adults. Despite the combination of novel therapeutical approaches, it remains a deadly malignancy with an abysmal prognosis. GBM is a polymorphic tumour from both molecular and histological points of view. It consists of different malignant cells and various stromal cells, contributing to tumour initiation, progression, and treatment response. GBM’s microenvironment is multifaceted and is made up of soluble factors, extracellular matrix components, tissue-resident cell types (e.g., neurons, astrocytes, endothelial cells, pericytes, and fibroblasts) together with resident (e.g., microglia) or recruited (e.g., bone marrow-derived macrophages) immune cells. These latter constitute the so-called immune microenvironment, accounting for a substantial GBM’s tumour volume. Despite the abundance of immune cells, an intense state of tumour immunosuppression is promoted and developed; this represents the significant challenge for cancer cells’ immune-mediated destruction. Though literature data suggest that distinct GBM’s subtypes harbour differences in their microenvironment, its role in treatment response remains obscure. However, an in-depth investigation of GBM’s microenvironment may lead to novel therapeutic opportunities to improve patients’ outcomes. This review will elucidate the GBM’s microenvironment composition, highlighting the current state of the art in immunotherapy approaches. We will focus on novel strategies of active and passive immunotherapies, including vaccination, gene therapy, checkpoint blockade, and adoptive T-cell therapies

Tumor response and outcome after reverse treatment for patients with synchronous colorectal liver metastasis: a cohort study.

The reverse treatment of patients with synchronous colorectal liver metastases (CRLM) is a sequential approach with systemic chemotherapy first, followed by liver resection, and finally, primary tumor resection. The aim of this study was to assess the feasibility, the radiological and pathological tumor response to neoadjuvant therapy, recurrence rates and long-term survival after reverse treatment in a cohort study. Data from patients with CRLM who underwent a reverse treatment from August 2008 to October 2016 were extracted from our prospective hepato-biliary database and retrospectively analyzed for response rates and survival outcomes. Radiological tumor response was assessed by RECIST (Response Evaluation Criteria In Solid Tumor) criteria and pathological response according to TRG (Tumor Regression Grade). Disease-free and overall survival were estimated with Kaplan-Meier survival curves. There were 44 patients with 19 rectal and 25 colonic tumors. The reverse treatment was fully completed until primary tumor resection in 41 patients (93%). Radiological assessment after chemotherapy showed 61% of complete/partial response. Pathological tumor response was major or partial in 52% of patients (TRG 1-3). Median disease-free survival after primary tumor resection was 10 months (95% CI 5-15 months). Disease-free survival at 3 and 5 years was 25% and 25%, respectively. Median overall survival was 50 months (95% CI 42-58 months). Overall survival at 3 and 5 years was 59% and 39%, respectively. The reverse treatment approach was feasible with a high rate of patients with complete treatment sequence and offers promising long-term survival for selected patients with advanced simultaneous colorectal liver metastases

Current Opinion and Knowledge on Peritoneal Carcinomatosis: A Survey among a Swiss Oncology Network.

The present survey aimed to evaluate current opinion and practice regarding peritoneal metastasis (PM), satisfaction with available treatment options, and need for new therapeutic approaches. This was a qualitative study conducted between October 2016 and October 2017 in the Réseau Suisse Romand d'Oncologie including 101 members of various oncological specialties. Participants' demographics, current practice, knowledge, and satisfaction regarding available treatment options and need for new treatment options were assessed by semantic differential scales through 33 closed questions with automatic reminders at 4-, 8-, 12-, and 16-week intervals. Twenty-seven participants (27%) completed the survey. Participants were gastrointestinal or gynecologic oncologists and surgeons. Most participants (67%) evaluated their knowledge on PM as moderate, while 22% considered themselves as experts. Clinical usefulness of systemic chemotherapy and hyperthermic intraperitoneal chemotherapy was judged to be moderate to high for PM of ovarian and colorectal origin and moderate to poor for gastric origin. Satisfaction with available treatment options was 6/10 (interquartile range [IQR] 4-7) for ovarian, 5/10 (IQR 3-7) for colorectal, and 3/10 (IQR 1-3) for gastric PM. Treatment strategies varied widely for typical case vignettes. The need for new treatment modalities was rated as 8/10 (IQR 6-10). Usefulness of and satisfaction with available treatment options for PM were rated as moderate at best by oncological experts, and treatment strategies differed importantly among participants. There appears to be a clear need for standardization and new treatment modalities

Impact of Pressurized Intraperitoneal Aerosol Chemotherapy on Quality of Life and Symptoms in Patients with Peritoneal Carcinomatosis: A Retrospective Cohort Study.

Background. Peritoneal cancer treatment aims to prolong survival, but preserving Quality of Life (QoL) under treatment is also a priority. Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) is a novel minimally invasive repeatable treatment modality. The aim of the present study was to assess QoL in our cohort of PIPAC patients. Methods. Analysis of all consecutive patients included from the start of PIPAC program (January 2015). QoL (0-100: optimal) and symptoms (no symptom: 0-100) were measured prospectively before and after every PIPAC procedure using EORTC QLQ-C30. Results. Forty-two patients (M : F = 8 : 34, median age 66 (59-73) years) had 91 PIPAC procedures in total (1 : 4x, 17 : 3x, 12 : 2x, and 12 : 1x). Before first PIPAC, baseline QoL was measured as median of 66 ± 2.64. Prominent complaints were fatigue (32 ± 4.3) and digestive symptoms as diarrhea (17 ± 3.75), constipation (17 ± 4.13), and nausea (7 ± 2.54). Overall Quality of Life was 64 ± 3.75 after PIPAC#1 (p = 0.57), 61 ± 4.76 after PIPAC#2 (p = 0.89), and 70 ± 6.67 after PIPAC#3 (p = 0.58). Fatigue symptom score was 44 ± 4.86 after PIPAC#1 and 47 ± 6.69 and 34 ± 7.85 after second and third applications, respectively (p = 0.40). Diarrhea (p = 0.31), constipation (p = 0.76), and nausea (p = 0.66) did not change significantly under PIPAC treatment. Conclusion. PIPAC treatment of peritoneal carcinomatosis had no negative impact on patients' overall QoL and its components or on main symptoms. This study was registered online on Research Registry (UIN: 1608)

Aging in an infinite-range Hamiltonian system of coupled rotators

We analyze numerically the out-of-equilibrium relaxation dynamics of a long-range Hamiltonian system of $N$ fully coupled rotators. For a particular family of initial conditions, this system is known to enter a particular regime in which the dynamic behavior does not agree with thermodynamic predictions. Moreover, there is evidence that in the thermodynamic limit, when $N\to \infty$ is taken prior to $t\to \infty$, the system will never attain true equilibrium. By analyzing the scaling properties of the two-time autocorrelation function we find that, in that regime, a very complex dynamics unfolds in which {\em aging} phenomena appear. The scaling law strongly suggests that the system behaves in a complex way, relaxing towards equilibrium through intricate trajectories. The present results are obtained for conservative dynamics, where there is no thermal bath in contact with the system. This is the first time that aging is observed in such Hamiltonian systems.Comment: Figs. 2-4 modified, minor changes in text. To appear in Phys. Rev.

The impact of the sars‐cov2 pandemic on a persuasive educational antimicrobial stewardship program in a university hospital in southern italy: A pre‐post study

Objectives: We evaluated the effect of the pandemic on the disruption of a persuasive educational antimicrobial stewardship program (ASP) conducted in a university hospital in southern Italy. Methods: In March 2020, the ASP, which began in January 2017 and was carried out at different times in 10 wards, was stopped due to the COVID‐19 pandemic. We conducted an observational study with interrupted time series analysis to compare the antibiotic consumption and costs, average length of hospital stay and in‐hospital mortality between 12 months before and 9 months after the interruption. Results: Four medical, four surgical wards and two ICUs were included in the study, for a total of 35,921 patient days. Among the medical wards we observed after the interruption a significant increase in fluoroquinolone use, with a change in trend (CT) of 0.996, p = 0.027. In the surgical wards, we observed a significant increase in the overall consumption, with a change in level (CL) of 24.4, p = 0.005, and in the use of third and fourth generation cephalosporins (CL 4.7, p = 0.003). In two ICUs, we observed a significant increase in piperacillin/tazobactam and fluoroquinolone consumption (CT 9.28, p = 0.019, and 2.4, p = 0.047). In the wards with a duration of ASP less than 30 months, we observed a significant increase in antibiotic consumption in the use of piperacillin/tazobactam and fluoroquinolones (CT 12.9, p = 0.022: 4.12, p = 0.029; 1.004, p = 0.011). Conclusions: The interruption of ASP during COVID‐19 led to an increase in the consumption of broad‐spectrum antibiotics, particularly in surgical wards and in those with a duration of ASP less than 30 months