UNASSIGNED: Anal squamous cell carcinoma (ASC) is a rare gastrointestinal malignancy showing an increased incidence over the past decades. YKL-40 is an immune modulator and pro-angiogenetic factor that showed a promising prognostic and predictive potential in several malignancies, but limited data are available for ASC. This study aims to provide an extensive evaluation of the prognostic and predictive role of YKL-40 in a multicenter cohort of ASC patients.
UNASSIGNED: We retrospectively retrieved 72 consecutive cases of ASC diagnosed between February 2011 and March 2021. Both serum and tissue protein expression of YKL-40 were assessed, the latter in ASC tumor cells and peritumor immune cells.
UNASSIGNED: Increased YKL-40 serum levels at the time of diagnosis were associated with older age (p = 0.035), presence of cardiovascular/metabolic comorbidities (p = 0.007), and death for any cause (p = 0.011). In addition, high serum levels of YKL-40 were associated with a poor prognosis (HR: 2.82, 95% CI: 1.01-7.84; p = 0.047). Protein expression of YKL-40 in ASC tumor cells was significantly associated with low tumor grade (p = 0.031), while the increased expression in peritumor immune cells was associated with a worse response of patients to chemoradiotherapy (p = 0.007). However, YKL-40 protein expression in ASC tumor cells or peritumor immune cells did not significantly impact patient overall survival.
UNASSIGNED: In conclusion, YKL-40 resulted a relevant prognostic (serum level) and predictive (tissue protein expression in peritumor immune cells) biomarker and can considerably improve ASC patient clinical management.

A complex series of studies by Oelschlegel et al. in a murine model of cerebral malaria establishes a temporal sequence of events linking decreased venous efflux to impaired perfusion, edema, and neuroinflammation. The relevance to human cerebral malaria is discussed, including the heterogeneity recognized in recent investigations of cerebrovascular hemodynamics.

In this review article four clinical comparative studies in axial spondylarthritis (axSpA) are presented and discussed. SURPASS as the only head-to-head study investigated the effect of adalimumab biosimilar disease-modifying antirheumatic drug (bsDMARD) or secukinumab on radiographic progression over a time period of 2 years. Overall, the radiographic progression of the spine was low and no significant difference between adalimumab bsDMARD or secukinumab was noted. The three other studies were not constructed as direct head-to-head studies but compared the efficacy of non-steroidal antirheumatic drugs (NSARD) with and without simultaneous treatment with biological DMARDs (bDMARD). The CONSUL study showed no statistically significant difference in the delay of radiographic progression of the spine over 2 years in radiographic axSpA (r-axSpA) patients, who underwent either combined treatment with golimumab and celecoxib or treatment with golimumab alone over 2 years. The ESTHER study showed that patients with early axSpA active inflammatory lesions, which were detected by whole-body magnetic resonance imaging (MRI), showed a significantly greater improvement under treatment with etanercept than those treated with sulfasalazine. The INFAST study showed that patients with early active axSpA who received a combined treatment of infliximab and naproxen, achieved a clinical remission twice as frequently as those who only received naproxen. Therefore, for the endpoint of radiological progression no difference could be shown in the inhibition of radiological progression between the mechanisms of action investigated. The comparative data for the endpoint of clinical efficacy showed that patients with bDMARDs showed a clearly better response to treatment than patients with NSAR or conventional synthetic DMARDs (csDMARD).
UNASSIGNED: In dieser Übersichtsarbeit werden 4 klinische Vergleichsstudien in der Indikation axiale Spondyloarthritis (SpA) vorgestellt und diskutiert. Die einzige direkte Vergleichsstudie SURPASS hatte das Ziel, das Aufhalten von röntgenologischer Progression mit entweder Adalimumab bs(Biosimilar)DMARD („disease-modifying antirheumatic drug“) oder Secukinumab über einen Zeitraum von 2 Jahren zu untersuchen. Insgesamt war die röntgenologische Progression der Wirbelsäule über 2 Jahre gering, wobei es keine signifikanten Unterschiede zwischen Adalimumab bsDMARD oder Secukinumab gab. Drei weitere Studien waren nicht direkt als Head-to-head-Studien angelegt, verglichen aber die Wirksamkeit von nichtsteroidalen Antirheumatika (NSAR) mit und ohne gleichzeitige Therapie mit b(„biological“)DMARD. In der CONSUL-Studie zeigte sich kein statistisch signifikanter Unterschied in der Verzögerung der röntgenologischen Progression der Wirbelsäule über 2 Jahre bei r(röntgenologisch)-axSpA(axiale Spondyloarthritis)-Patienten, die entweder eine Kombinationstherapie mit Golimumab und Celecoxib oder eine Golimumab-Monotherapie über 2 Jahre erhalten hatten. Die ESTHER-Studie zeigte, dass sich bei Patienten mit früher axSpA aktive entzündliche Läsionen, die durch Ganzkörper-MRT (Magnetresonanztomographie) nachgewiesen wurden, unter einer Therapie mit Etanercept signifikant stärker als bei mit Sulfasalazin behandelten Patienten verbesserten. Die INFAST-Studie zeigte bei Patienten mit früher, aktiver axSpA, dass Patienten, die eine Kombinationstherapie aus Infliximab und Naproxen erhielten, doppelt so häufig eine klinische Remission erreichten wie Patienten, die nur Naproxen erhielten. Damit konnte für die Endpunkte der Röntgenprogression kein Unterschied in der Hemmung der Röntgenprogression zwischen den untersuchten Wirkprinzipien gezeigt werden. Die Vergleichsdaten für den Endpunkt der klinischen Wirksamkeit zeigten, dass Patienten mit bDMARD ein deutlich besseres Therapieansprechen zeigten als Patienten mit NSAR oder cs(„conventional synthetic“)DMARD.

BACKGROUND: Highly effective modulators of the CFTR channel have been demonstrated to dramatically impact disease progression and outcome. However, real-world data indicates that the magnitude of the clinical benefit is not equal among all patients receiving the treatment. We aimed to assess the variability in treatment response (as defined by the 6-month change in sweat chloride concentration, forced expiratory volume in one second [ppFEV1], body mass index [BMI], and CF Questionnaire-Revised [CFQ-R] respiratory domain score) and identify potential predictors in a group of patients receiving Elexacaftor-Tezacaftor-Ivacaftor (ETI) triple combination therapy.
METHODS: This was a single-center, prospective cohort study enrolling adults with CF at a major center in Italy. We used linear regression models to identify a set of potential predictors (including CFTR genotype, sex, age, and baseline clinical characteristics) and estimate the variability in treatment response.
RESULTS: The study included 211 patients (median age: 29 years, range: 12-58). Median changes (10-90th percentile) from baseline were: - 56 mEq/L (-76; -27) for sweat chloride concentration, +14.5 points (2.5; 32.0) for ppFEV1, +0.33 standard deviation scores (-0.13; 1.05) for BMI and +17 points (0; 39) for the CFQ-R respiratory domain score. The selected predictors explained 23 % of the variability in sweat chloride concentration changes, 18 % of the variability in ppFEV1 changes, 39 % of the variability in BMI changes, and 65 % of the variability in CFQ-R changes.
CONCLUSIONS: This study highlights a high level of heterogeneity in treatment response to ETI, which can only be partially explained by the baseline characteristics of the disease.

Background: Response to antipsychotics is subject to a wide interindividual variability, due to genetic and non-genetic factors. Several single nucleotide polymorphisms (SNPs) have been associated with response to antipsychotics in genome-wide association studies (GWAS). Polygenic risk scores (PRS) are a powerful tool to aggregate into a single measure the small effects of multiple risk alleles. Materials and methods: We studied the association between a PRS composed of SNPs associated with response to antipsychotics in GWAS studies (PRSresponse) in a real-world sample of patients (N = 460) with different diagnoses (schizophrenia spectrum, bipolar, depressive, neurocognitive, substance use disorders and miscellaneous). Two other PRSs composed of SNPs previously associated with risk of schizophrenia (PRSschizophrenia1 and PRSschizophrenia2) were also tested for their association with response to treatment. Results: PRSresponse was significantly associated with response to antipsychotics considering the whole cohort (OR = 1.14, CI = 1.03-1.26, p = 0.010), the subgroup of patients with schizophrenia, schizoaffective disorder or bipolar disorder (OR = 1.18, CI = 1.02-1.37, p = 0.022, N = 235), with schizophrenia or schizoaffective disorder (OR = 1.24, CI = 1.04-1.47, p = 0.01, N = 176) and with schizophrenia (OR = 1.27, CI = 1.04-1.55, p = 0.01, N = 149). Sensitivity and specificity were sub-optimal (schizophrenia 62%, 61%; schizophrenia spectrum 56%, 55%; schizophrenia spectrum plus bipolar disorder 60%, 56%; all patients 63%, 58%, respectively). PRSschizophrenia1 and PRSschizophrenia2 were not significantly associated with response to treatment. Conclusion: PRSresponse defined from GWAS studies is significantly associated with response to antipsychotics in a real-world cohort; however, the results of the sensitivity-specificity analysis preclude its use as a predictive tool in clinical practice.

OBJECTIVE: To assess the effectiveness of amitriptyline (AMT), and to identify the determinants of the treatment\'s effectiveness in patients diagnosed with burning mouth syndrome (BMS).
BACKGROUND: Treatment of BMS is challenging and no established treatment protocol is available. AMT may be an important treatment option, cout not all patients benefit from this drug. Studies assessing factors related to treatment response are valuable in improving decision-making.
METHODS: This case series study examined the medical records of all patients diagnosed with BMS at an oral medicine unit in a university hospital from 2008 to 2022. The patients were divided into responders to AMT and non-responders to AMT. Data on demographic information, comorbidities, medications, types of symptoms and oral subsites affected were collected. Descriptive and bivariate analyses were conducted to assess the association between the independent variables and the outcome, using the Chi-squared test (P < .05).
RESULTS: Three hundred and fourty-nine patients reported a burning mouth sensation, 50 of them (14.3%) being diagnosed with primary BMS. Of these, 35 were treated with AMT, and 26 (74.2%) responded significantly to AMT. All males responded to AMT, whereas only 67.9% of females responded. The mean dose of AMT among responders was 29.8 ± 12.3 mg, with most patients achieving a response with 25 mg (61.5% of patients), followed by 50 mg (23%). The concomitant use of an anticonvulsant resulted in non-response.
CONCLUSIONS: AMT may be effective in BMS management for most patients.

There is currently no consensus to determine which advanced melanoma patients will benefit from targeted therapy, immunotherapy, or a combination of both, highlighting the critical need to identify early-response biomarkers to advanced melanoma therapy. The goal of this review is to provide scientific rationale to highlight the potential role of metabolic imaging to assess response to targeted and/or immune therapy in melanoma cancer. For that purpose, a brief overview of current melanoma treatments is provided. Then, current knowledge with respect to melanoma metabolism is described with an emphasis on major crosstalks between melanoma cell metabolism and signaling pathways involved in BRAF-targeted therapy as well as in immune checkpoint inhibition therapies. Finally, preclinical and clinical studies using metabolic imaging and/or profiling to assess response to melanoma treatment are summarized with a particular focus on PET (Positron Emission Tomography) imaging and 13C-MRS (Magnetic Resonance Spectroscopy) methods.

Response to antidepressants is related to hippocampal neurogenesis integrity, a process mediated by neurotrophins, such as Brain Derived Neurotrophic Factor (BDNF). In turn, pro-inflammatory state appears to reduce neurogenesis, and has been associated with refractory depressive states. We propose to analyze the human neural progenitor cells derived from the olfactory epithelium (HNPCs-OE) as an indicator of neurogenesis in humans. Therefore, we compared the number and content of HNPCs-OE in depressed patients taking antidepressants, according to response to treatment. Twenty depressed patients were followed during eight weeks after antidepressant treatment was prescribed. At the end evaluation they were divided in two groups according to Hamilton depression rating scale (HDRS) scores: responders and non-responders. We compared the number and components of HNPCs-OE between groups and observed an elevation of interleukine-8 in those patients who do not achieve response to treatment, BDNF levels were no related to antidepressant response.

Aplastic anemia (AA) is a rare, life-threatening hematological disease, with a poorly defined incidence. As the data available on AA varies substantially worldwide, a multicenter, ambispective, observational study was carried out between 2010 and 2019 to assess the incidence, clinical management and survival of AA at seven Spanish hospitals. The incidence of AA was 2.83 per million inhabitants per year, consistent with that reported previously in Europe, with a median age at diagnosis of 61 years-old (range 12-86), and a similar number of males and females. The initial diagnosis was severe or very severe AA in 55.8% of cases and 93.7% required transfusion. The most frequent first line therapy was anti-thymocyte globulin (ATG) plus cyclosporin A (CsA, 44.2%), followed by other CsA-based regimes (46.3%), with hematopoietic stem cell transplantation an infrequent 1st line therapy. The 6-month response rate was 68.2%, which then increased over a median follow-up of 3.9 years. The 5-year overall survival (5OS) was 73.6%, similar in severe (78.6%) and very severe AA patients (74.6%) but lower in moderate AA (MAA) patients (68.4%). The 5OS was 100% in 0-25 year-old patients but dropping to 58.3% in patients ≥ 60 years-old. At the last contact, 75.8% of the patients were alive. In conclusion, the incidence, characteristics and management of AA in our study are consistent with that reported previously. In terms of survival, although the global long-term OS rate was good, there is room for improvement, particularly in older patients. Finally, what appears to be a worse long-term survival of MAA patients, as reported previously, reinforces the importance of not underestimating this condition when diagnosed as MAA.

UNASSIGNED: Periodontitis is a chronic infectious disease affecting periodontium having multifactorial etiology, can cause significant systemic challengein addition to localized inflammation, tissue damage, and bone resorption. A serological marker of systemic inflammation known as C-reactive protein has been linked to an increased risk for a number of pathological conditions, including cardiovascular diseases.
UNASSIGNED: To estimate levels of serum C-reactive protein in healthy individuals and subjects with periodontal diseases and to compare serum C-reactive protein levels in subjects having periodontal disease pre-operatively & post-operatively.
UNASSIGNED: The study was conducted on 60 subjects age ranging from 35 to 60 years. 30 individuals with healthy periodontium were in group 1 (control group) and the remaining 30 were diagnosed as adult periodontitis were in group 2 (experimental group). Periodontal examination done using gingival index, plaque index, periodontal pocket depth, and Russel\'s index. CRP levels were examined between group 1 and group 2 and in group 2 between baseline visit before treatment and 2 months after treatment.
UNASSIGNED: The findings of this study show a significant connection between periodontal disease and the inflammatory marker CRP in the body, as well as a tendency for a significant decrease in serumCRP levels following periodontitis therapy. At baseline, there was a positive correlation among C-reactive protein, probing pocket depth, and Russell\'s index.
UNASSIGNED: As CRP is a key mediator for cardiovascular disease, an increase in C- reactive protein levels in periodontal diseases suggests a significant connection between periodontitis and cardiovascular diseases. Early periodontal treatment might decrease the severity of cardiovascular disease that already exists. This suggests that periodontal examination should be part of routine practicealong with cardiovascular examination.