Computational and Experimental Evaluation of the Immune Response of Neoantigens for Personalized Vaccine Design.

In the last few years, the importance of neoantigens in the development of personalized antitumor vaccines has increased remarkably. In order to study whether bioinformatic tools are effective in detecting neoantigens that generate an immune response, DNA samples from patients with cutaneous melanoma in different stages were obtained, resulting in a total of 6048 potential neoantigens gathered. Thereafter, the immunological responses generated by some of those neoantigens ex vivo were tested, using a vaccine designed by a new optimization approach and encapsulated in nanoparticles. Our bioinformatic analysis indicated that no differences were found between the number of neoantigens and that of non-mutated sequences detected as potential binders by IEDB tools. However, those tools were able to highlight neoantigens over non-mutated peptides in HLA-II recognition (p-value 0.03). However, neither HLA-I binding affinity (p-value 0.08) nor Class I immunogenicity values (p-value 0.96) indicated significant differences for the latter parameters. Subsequently, the new vaccine, using aggregative functions and combinatorial optimization, was designed. The six best neoantigens were selected and formulated into two nanoparticles, with which the immune response ex vivo was evaluated, demonstrating a specific activation of the immune response. This study reinforces the use of bioinformatic tools in vaccine development, as their usefulness is proven both in silico and ex vivo.

Characteristics and outcomes of advanced melanoma patients with complete response and elective discontinuation of first-line anti-programmed death-1 monotherapy: A real-world multicentre observational cohort study.

Anti-programmed death-1 (anti-PD1) treatment has significantly improved outcomes of advanced melanoma with a considerable percentage of patients achieving complete response (CR). This real-world study analyzed the feasibility of elective anti-PD1 discontinuation in advanced melanoma patients with CR and evaluated factors related to sustained response. Thirty-five patients with advanced cutaneous or primary unknown melanoma with CR to nivolumab or pembrolizumab from 11 centers were included. Mean age was 66.5 years, and 97.1% had ECOG PS 0-1. 28.6% had ≥3 metastatic sites with 58.8% having M1a-M1b disease; 8.6% had liver and 5.7% had brain metastases. At baseline, 80% had normal LDH, and 85.7% had a neutrophil-to-lymphocyte ratio ≤3. 74.3% of patients had CR confirmed in PET-CT. Median duration of anti-PD1 was 23.4 months (range 1.3-50.5). 24 months after therapy discontinuation, 91.9% of patients were progression-free. Estimated PFS and OS at 36, 48, and 60 months from the start of anti-PD1 were 94.2%, 89.9%, 84.3%, and 97.1%, 93.3%, 93.3%, respectively. Antibiotics use after anti-PD1 discontinuation increased the odds of progression (OR 16.53 [95% CI 1.7, 226.03]). The study confirms the feasibility of elective anti-PD1 discontinuation in advanced melanoma patients with CR and favorable prognostic factors at baseline.

Appetite disorders in cancer patients: Impact on nutritional status and quality of life.

Cancer patients are at high risk of malnutrition due to several symptoms such as lack of appetite. The aim of this study was to determine the prevalence of different appetite disorders in cancer patients and their influence on dietary intake, nutritional status, and quality of life. We conducted a cross-sectional study of cancer patients at risk of malnutrition. Nutritional status was studied using Subjective Global Assessment, anthropometry, and grip strength. Dietary intake was evaluated with a 24-h recall, and patients were questioned about the presence of changes in appetite (none, anorexia, early satiety, or both). Quality of life was measured using EORTC-QLQ-C30. Multivariate analysis was performed using linear regression. 128 patients were evaluated. 61.7% experienced changes in appetite: 31% anorexia, 13.3% early satiety, and 17.2% both. Appetite disorders were more common in women and with the presence of cachexia. The combination of anorexia and satiety resulted in a lower weight and BMI. However, there were no significant effects on energy or macronutrient intake among different appetite alterations. Patients with a combination of anorexia and early satiety had worse overall health perception, role function, and fatigue. Appetite disorders are highly prevalent among cancer patients at risk of malnutrition. They have a significant impact on nutritional status and quality of life, especially when anorexia and early satiety are combined.

A Modified Single-Step Method to Repair a Central Defect of the Upper Lip.

INTRODUCTION: Defects in the central region of the upper lip are difficult to repair. DISCUSSION: Several techniques have been described, many of them requiring a second surgical procedure to obtain acceptable aesthetic results. CASE REPORT: A patient with a soft defect in the central region of the upper lip following aggression by human bite is presented. To repair the defect, the principles described by Goldstein for lateral lip defects were used (Goldstein in Plast Reconstr Surg 85(3):446-452, 1990; Robotti et al. in J Plast Reconstr Aesthet Surg 63:431-439, 2010). CONCLUSION: In this particular case, two full-thickness advancing miomucosal flaps from the vermilion of the upper lip were used with predictable aesthetic results.

Vagus Nerve Paraganglioma: Radiological Features We Should Be Aware of.

INTRODUCTION: A rare case of vagal paraganglioma is reported. MATERIAL AND METHODS: The specific radiological features of this tumor are presented to the clinician in order to make presumptive diagnosis. CONCLUSION: By CT-scan and/or MRI it must be suspected when a hypervascular tumor in relation to the major cervical vessels displaces the internal and external carotid arteries forward, does not open the carotid bifurcation, and displaces the internal jugular vein backwards.

Schwannoma of tongue.

The schwannomas are nervous tissue tumors. We report a case of schwannoma of oral tongue. Because schwannomas are quite rare in the oral cavity, they are often not immediately included in the differential diagnosis of oropharyngeal masses, causing delay in identification and treatment. The definitive diagnosis requires histopathologic examination.

Osteomyelitis of the mandible in a patient with osteopetrosis. Case report and review of the literature.

Osteopetrosis is a rare hereditary bone disorder presenting with variable clinical features and is characterized by an increase in bone density and reduction of marrow spaces that result from a defect in the function of osteoclasts and, consequently, a decrease in bone turnover. This disease is generally divided into three types: severe infantile malignant autosomal recessive, intermediate mild autosomal recessive, and benign autosomal dominant. The prognosis of the first two types is very poor and is characterized by an early onset, usually within the first decade of life, and early death. The benign-type is characterized by a later onset and a longer life span. Ten percent of osteopetrosis cases develop osteomyelitis that usually involves the mandible. The osteomyelitis is generally caused by tooth extraction or pulpal necrosis. The leading cause of the increased rate of infection is thought to be a lack of adequate bone vasculature. Treatment of osteomyelitis secondary to osteopetrosis is controversial. Treatment regimens include high-dose systemic antibiotics coupled with thorough debridement of necrotic bone and primary closure of soft tissues, if possible. Hyperbaric oxygen has been used for the treatment of chronic osteomyelitis.

[Positional vertigo. Symptom, clinical sign, or disease?]. / Vértigo posicional. Síntoma, signo o enfermedad?

INTRODUCTION: We present a prospective study with the aim of assessing the differences found between position-triggered vertiginous syndromes, those diagnosed as benign paroxysmal positional vertigos (BPPV) in primary care and non-specific clinics, and those classified as BPPV at an otoneurology unit. PATIENTS AND METHOD: Over a 17 month period, 432 consecutive patients were included after evaluation at a otoneurology unit receiving all referrals for vestibular pathologies. The existence of trigger factors was investigated, as was the distribution of the diagnoses associated with a positional trigger. The characteristics of the patients with a final diagnosis of BPPV were also studied. RESULTS: Of this population, 217 patients (50.23%) reported a positional change as the trigger for their symptoms, 106 (24.53%) were referred from their initial care centres with a diagnosis of BPPV, and 128 (29.62%) were classified as truly BPPV. The coincidence between the preliminary diagnosis and the definitive one was 52.8%. A history of positional paroxysmal vertigo during seconds was linked to BPPV in 78% of cases. Only in 4.7% of the BPPV cases diagnosed at the otoneurology unit had provoking manoeuvres been performed. CONCLUSIONS: We have found that an adequate anamnesis is capable of providing accurate guidance for diagnostic purposes in most cases of BPPV, but the performance of provoking manoeuvres and the correct specific treatment for this pathology is of paramount importance when classifying a patient with suspected BPPV.