Good clinical response to cemiplimab in a young patient with locally advanced cutaneous squamous cell carcinoma on preexisting recessive dystrophic epidermolysis bullosa.

Recessive dystrophic epidermolysis bullosa (RDEB) is a rare genetic skin disease caused by mutations in the type VII collagen gene (COL7A1; 3p21.31). Mutations in this gene lead to an alteration in function or reduced amounts of collagen VII. This alteration of collagen VII leads to skin fragility and lesions at minor injuries with difficult healing. Cutaneous squamous cell carcinoma (cSCC) is more frequent in patients with RDEB than in the general population because of chronic wound formation; it constitutes a major cause of morbidity and is often cited as a cause of death for these patients. There is little experience with the treatment of cSCC in patients with RDEB. We report the case of a 19-year-old female patient with RDBE and inoperable locally advanced cSCC of the left arm. Because of the lack of therapy options, therapy with cemiplimab was started at a dose of 350 mg administered intravenously every 3 weeks. A confirmed clinical response was observed after the second cycle of treatment with no toxicity. During follow-up, the patient had a notable clinical response with no auto-immune adverse reactions. This shows that cemiplimab has a good safety profile for cSCC in patients with RDEB and is a valuable therapy option.

Cancer Pain and Non-Invasive Brain Stimulation-A Narrative Review.

Background and Objectives: Pain is the most prevalent symptom in cancer patients. There is a paucity of data regarding non-invasive brain stimulation (NIBS) for the treatment of chronic pain in patients with cancer. The purpose of this article is to review the techniques of NIBS and present the published experiences of the oncological population. Materials and Methods: Databases including MEDLINE, Scopus, Web of Science, and the Cochrane Library were searched for articles on cancer patients with pain that was managed with non-invasive brain stimulation techniques. We included articles in English that were published from inception to January 2023. As studies were limited in number and had different designs and methodologies, a narrative review was considered as the best option to integrate data. Results: Four studies focusing on transcranial magnetic stimulation, six articles on transcranial direct current stimulation, and three articles regarding cranial electric stimulation were found and reviewed. Conclusions: Data are limited and not robust. Further studies in this field are required. Guidelines on NIBS for non-malignant chronic pain conditions provide good premises for cancer-related chronic pain.

Nivolumab/Relatlimab-rmbw: A Novel Dual Combination Therapy to Treat Adult and Pediatric Patients With Unresectable or Metastatic Melanoma.

BACKGROUND: Immune checkpoint inhibitors control effector mechanisms and work to restore downregulated T-cells in patients with melanoma. Examples of such include programmed death-1 inhibitors and lymphocyte-activating gene 3 inhibitors. The combination of nivolumab, a programmed death-1 inhibitor, and relatlimab-rmbw, a lymphocyte-activating gene 3 inhibitor, has shown antitumor activity and improved progression-free survival in patients with unresectable or metastatic melanoma. MECHANISM OF ACTION PHARMACOKINETICS/PHARMACODYNAMICS: The fixed-dose combination of nivolumab and relatlimab immunotherapy is approved for adults and pediatrics 12 years of age or older with metastatic or unresectable melanoma. Volume of distribution is 6.6 L for relatlimab and nivolumab, and half-life is 27 and 26 days, respectively. Clearance at steady state is 7.6 mL/h for nivolumab and 5.5 mL/h for relatlimab. Sex, age, race, and mild hepatic/renal impairment had no clinical effect on clearance. The exposure-response relationship and pharmacodynamic response for the safety and effectiveness of nivolumab/relatlimab-rmbw have not been fully characterized. Safety concerns include severe and fatal immune-mediated adverse reactions, infusion-related reactions, and complications of allogeneic hematopoietic stem cell transplantation, and fetal toxicity. Dosing is determined by patient's age and weight. Solution is infused over a 30-minute timeframe. CLINICAL TRIALS: In the RELATIVITY-047 trial, patients received nivolumab or nivolumab/relatlimab-rmbw. Results showed superiority of dual therapy over monotherapy with a progression-free survival of 10.1 months (95% CI, 6.4-15.7) compared with 4.6 months (95% CI, 3.4-5.6) and hazard ratio of 0.75 (95% CI, 0.62-0.92); P = 0.006, respectively. No safety concerns were observed compared with monotherapy with treatment-related adverse events occurring in 18.9% of patients on combination therapy compared with 9.7% on nivolumab alone. THERAPEUTIC ADVANCE: The novel mechanism and improvement in progression-free survival compared with standard of care highlight the therapeutic advancement of nivolumab/relatlimab-rmbw in the treatment of unresectable and metastatic melanoma.

Exploring the Influence of Age, Gender and Body Mass Index on Colorectal Cancer Location.

Background and objectives: The global burden of non-communicable diseases like obesity and cancer, particularly colorectal cancer (CRC), is increasing. The present study aimed to investigate the association between CRC location (proximal vs. distal) and patient demographic factors including age, sex, and BMI, as well as cancer stage at diagnosis. Materials and Methods: In this cross-sectional study, data from 830 patients diagnosed with CRC were analyzed. The variables included age, sex, weight, height, BMI, cancer location, and cancer stage at diagnosis. Patients were stratified into three age groups and three BMI categories, and we analyzed the association between cancer location and these variables using Chi-squared tests and multivariate logistic regression. Results: The rectum and ascending colon were the most common locations of malignant neoplasms. No statistically significant differences in cancer location across age groups were observed. Significant differences were found in the BMI across age groups, particularly in the normal weight and overweight categories. Normal weight and obese patients had a higher proportion of Stage 3 and Stage 4 cancers. Obesity emerged as a significant predictor for rectal cancer in a multivariate logistic regression analysis, with an odds ratio of 1.56. However, no significant associations were found between cancer location and other factors like age, gender, or cancer stage. Conclusions: Our study revealed that normal weight and obese patients had a higher proportion of Stage 3 and Stage 4 cancers, with obesity emerging as a significant predictor for rectal cancer. It is important to note that while obesity was found to be a significant predictor for rectal cancer, the development and location of colorectal cancer is likely influenced by various factors beyond those studied here. Therefore, further research is needed to investigate the roles of other potential risk factors, like loss of SIRT6 and adipose tissue homeostasis. Additionally, inflammation associated with microbiota in the colorectal mucosa, systemic gene expression, and visceral obesity may also play important roles in the development and progression of colorectal cancer. Understanding these intricate relationships is crucial for better screening, disease prognosis, and management strategies.

T-RAC: Study protocol of a randomised clinical trial for assessing the acceptability and preliminary efficacy of adding an exergame-augmented dynamic imagery intervention to the behavioural activation treatment of depression.

BACKGROUND: Improving the existent effective treatments of depression is a promising way to optimise the effects of psychological treatments. Here we examine the effects of adding a rehabilitation type of imagery based on exergames and dynamic simulations to a short behavioural activation treatment of depression. We investigate the acceptability and the efficacy of an exergame-augmented dynamic imagery intervention added to behavioural activation treatment and associated mechanisms of change. METHODS AND ANALYSES: In a two-arm pilot randomised controlled trial, the acceptability and preliminary efficacy of an exergame-augmented dynamic imagery intervention added to behavioural activation treatment for depressed individuals will be assessed. Participants (age 18-65) meeting criteria for depression are recruited by media and local announcements. 110 participants will be randomly allocated to behavioural activation plus imagery group or to standard behavioural activation group. The primary outcome is depressive symptom severity (Beck Depression Inventory II) and secondary outcomes are anhedonia, apathy and behavioural activation and avoidance. The outcomes are assessed at baseline, mid treatment, posttreatment and 3-month follow-up. Moderation and mediation analyses will be explored. An intention-to-treat approach with additional per-protocol analysis will be used for data analysis.

Associations between Body Mass Index and Prostate Cancer: The Impact on Progression-Free Survival.

Background and objectives: This study aimed to evaluate the impact of body mass index on PCa outcomes in our institution and also to find if there are statistically significant differences between the variables. Materials and Methods: A retrospective chart review was performed to extract information about all male patients with prostate cancer between 1 February 2015, and 25 October 2022, and with information about age, weight, height, follow-up, and PSA. We identified a group of 728 patients, of which a total of 219 patients resulted after the inclusion and exclusion criteria were applied. The primary endpoint was progression-free survival, which was defined as the length of time that the patient lives with the disease, but no relapses occur, and this group included 105 patients. In this case, 114 patients had a biological, local or metastatic relapse and were included in the progression group. Results: Our study suggests that prostate cancer incidence rises with age (72 ± 7.81 years) in men with a normal BMI, but the diagnostic age tends to drop in those with higher BMIs, i.e., overweight, and obese in the age range of 69.47 ± 6.31 years, respectively, 69.1 ± 7.51 years. A statistically significant difference was observed in the progression group of de novo metastases versus the absent metastases group at diagnostic (p = 0.04). The progression group with metastases present (n = 70) at diagnostic had a shorter time to progression, compared to the absent metastases group (n = 44), 18.04 ± 11.37 months, respectively, 23.95 ± 16.39 months. Also, PSA levels tend to diminish with increasing BMI classification, but no statistically significant difference was observed. Conclusions: The median diagnostic age decreases with increasing BMI category. Overweight and obese patients are more likely to have an advanced or metastatic prostate cancer at diagnosis. The progression group with metastatic disease at diagnostic had a shorter time to progression, compared to the absent metastases group. Regarding prostate serum antigen, the levels tend to become lower in the higher BMI groups, possibly leading to a late diagnosis.

Analysis of breast cancer subtypes and their correlations with receptors and ultrasound.

The study aim was to evaluate the ultrasound (US) signs of the mammary lesions classified in the Breast Imaging-Reporting and Data System (BI-RADS) score category 3, 4, and 5, corresponding to US BI-RADS. It also followed the correlation between US changes of lesions suggestive for malignancy with the histopathological results and evaluated the proper management of those lesions. There were correlations of breast cancer (BC) subtypes with the receptors [estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2)], and Ki67 index, and the signs of conventional ultrasonography and US elastography. We selected 108 female patients examined with US, mammography and fine-needle biopsy who presented suspicions for malignancy lesions. Following the immunohistochemical analysis, they were classified in one of the BC subtypes. According to chi-squared analysis of molecular cancer subtypes correlation to receptors and Ki67 index, we found significant associations between both luminal A and luminal B HER2-negative subtypes and hormone receptors (ER, PR). These have an inverse relationship with Ki67 index elevated values; luminal B HER2-positive subtype has a direct association with HER2 presence; HER2-enriched subtype was statistically significant associated to HER2 presence and elevated Ki67 index values but had an inverse relationship to hormone receptors (ER, PR); triple-negative subtype was strongly associated to Ki67 index values and inversely correlated to ER and PR. We found luminal A subtype as being the most common and luminal B HER2-positive subtype as having the fewer cases.

Common Pathways for Pain and Depression-Implications for Practice.

BACKGROUND: Pain and depression have a high impact on caring for the people who need palliative care, but both of these are neglected compared with the approach for other symptoms encountered by these patients. AREAS OF UNCERTAINTY: There are few studies in humans that support the existence of common neural circuits between depression and pain that also explore the use of drugs with effects in both conditions. More knowledge is needed about the relationship of these clinical entities that will lead to the optimization of the treatment and improvement of quality of life. DATA SOURCES: We conducted a search in PubMed to identify relevant articles and reviews that have been published in the last 5 years, concerning the topic of common pathways between depression and pain (2014-April 2019). THERAPEUTIC ADVANCES: The connections between the 2 clinical entities start at the level of the cortical regions. The hippocampus is the main site of neural changes, modification of the immune system, neuromodulators, neurotransmitters, and signaling pathways implicated in both conditions. Increased levels of peripheral proinflammatory cytokines and neuroinflammatory changes are related to the physiopathology of these entities. Inflammation links depression and pain by altering neural circuits and changes in their common cortical regions. Antidepressants are used to treat depression and chronic, pain but more experimental studies are needed to determine which antidepressant drugs are the most effective in treating the 2 entities. CONCLUSIONS: Pharmacological and nonpharmacological interventions targeting cortical changes in pain and depression are promising, but more clinical studies are needed to validate their usefulness.

Elevations in High-Sensitive Cardiac Troponin T and N-Terminal Prohormone Brain Natriuretic Peptide Levels in the Serum Can Predict the Development of Anthracycline-Induced Cardiomyopathy.

BACKGROUND: Anthracyclines remain the cornerstone of the treatment in many cancers including lymphomas, leukemia and sarcomas, and breast cancer. The cardiomyopathy that develops from anthracyclines can lead to heart failure and decreased survival. Multiple mechanisms are involved in the pathophysiology of anthracycline-induced heart failure. STUDY QUESTION: We hypothesize that anthracycline-induced cardiac (AIC) pathology can be monitored using a panel of blood biomarkers including high-sensitive cardiac troponin T (hs-cTnT) for myocyte necrosis and N-terminal prohormone brain natriuretic peptide (NT-proBNP) for parietal stress. STUDY DESIGN: A prospective, institutionally approved study recruited all patients with cancer scheduled to start anthracycline chemotherapy in the Transylvania University cancer clinics. MEASURES AND OUTCOMES: Transthoracic 2D echocardiography and the measurements of NT-proBNP and hs-cTnT plasma levels were performed at the beginning of the study and 3 months and 6 months after anthracycline treatment initiation. RESULTS: The plasma levels of hs-cTnT at 3 months (rho = 0.439, P = 0.0001) and 6 months (rho = 0.490, P = 0.0001) are correlated with AIC occurrence. For a cutoff value of hs-cTnT at 3 months > 0.008 ng/mL, we obtained 66.7% sensitivity and 67.9% specificity for developing AIC at 6 months, with a 54.5% positive predictive value and a 87.8% negative predictive value. The NT-proBNP serum levels at 3 months (rho = 0.495, P = 0.0001) and 6 months (rho = 0.638, P = 0.0001) are correlated with an AIC diagnosis at 6 months. For a cutoff value of NT-proBNP at 3 months >118.5 pg/mL, we obtained 80% sensitivity and 79.2% specificity for evolution to AIC at 6 months, with 52.2% positive predictive value and 93.3% negative predictive value. CONCLUSIONS: In anthracycline-treated cancer patients, the increase in plasma levels of NT-proBNP and of hs-cTnT can predict the development of anthracycline-induced cardiomyopathy. Early identification of at-risk patients will potentially allow for targeted dose reductions and will diminish the number of patients developing cardiac pathology.

Adjunctive use of InGaAsP and Er,Cr:YSGG lasers in nonsurgical periodontal therapy: a randomized controlled clinical study.

OBJECTIVE: To evaluate clinically and microbiologically the outcomes following the combined application of InGaAsP diode laser and Er,Cr:YSGG laser for nonsurgical treatment of chronic periodontitis (ChP). METHOD AND MATERIALS: Forty-two patients (age 45.31 ± 9.78 years, 22 female, 23 smokers) with ChP were randomly treated with subgingival debridement (SD) by means of ultrasonic and hand instruments (control group, n = 21) or with InGaAsP followed 1 week later by InGaAsP + SD + Er,Cr:YSGG (test group, n = 21). In the test group, a second laser treatment was performed for all residual sites (bleeding sites with probing depth [PD] ≥ 4 mm) 2 months after the first laser therapy. At baseline and 6 months after therapy, periodontal clinical and microbiologic parameters were evaluated. RESULTS: Six months after therapy, statistically significant clinical and microbiologic improvements (PD reduction, clinical attachment level [CAL] gain, quantitative reduction of periopathogens) were observed in both groups compared to baseline. However, the use of InGaAsP followed by SD and the adjunctive use of an Er,Cr:YSGG laser, yielded statistically significantly higher clinical (PD, CAL, bleeding on probing, number of sites with PD ≥ 5 mm, PD ≥ 6 mm, PD ≥ 7 mm) and microbiologic (Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia, Prevotella intermedia, Peptostreptococcus micros, Fusobacterium nucleatum) improvements (P < .05) compared to SD alone. CONCLUSIONS: In patients with ChP, the adjunctive use of InGaAsP and Er,Cr:YSGG to SD may additionally improve the clinical and microbiologic parameters obtained with SD alone, thus representing a valuable approach in nonsurgical periodontal therapy.