Interleukin-1 Blockers in Recurrent and Acute Pericarditis: State of the Art and Future Directions.

Diseases of the pericardium encompass a spectrum of conditions, including acute and recurrent pericarditis, where inflammation plays a pivotal role in the pathogenesis and clinical manifestations. Anti-inflammatory therapy indeed forms the cornerstone of treating these conditions: NSAIDs, colchicine, and corticosteroids (as a second-line treatment) are recommended by current guidelines. However, these medications come with several contraindications and are not devoid of adverse effects. In recent years, there has been an increased focus on the role of the inflammasome and potential therapeutic targets. Recurrent pericarditis also shares numerous characteristics with other autoinflammatory diseases, in which interleukin-1 antagonists have already been employed with good efficacy and safety. The objective of this review is to summarize the available studies on the use of anti-IL-1 drugs both in acute and recurrent pericarditis.

Clinical, histopathological, and molecular characterization of canine pigmented viral plaques.

Canine pigmented viral plaques (PVPs) are proliferative epidermal lesions caused by canine papillomaviruses (CPVs). Although the lesions are benign, neoplastic transformation has been reported. Cases reported in the literature are few and mainly focused on genome sequencing. The aim of this study was to collect data on the epidemiology, clinicopathological features, and genotyping of PVPs. Fifty-five canine PVPs were retrospectively retrieved and histologically evaluated. Follow-up was available for 33 cases. The median age was 6.5 years and pugs were the most represented breed (25%). There were 4 clinical presentations: a single lesion (24%), multiple lesions (75%) in one (41%) or different sites (34%), and generalized lesions all over the body (24%). The abdomen and axillae were the most common sites. In single lesions, no recurrence was observed after conventional surgery, whereas different medical treatments reported for multiple lesions were not successful. Spontaneous regression was reported in 3 cases. Neoplasia in contiguity with PVPs was seen in 5 of 55 lesions (9%), and 1 dog was euthanized due to invasive squamous cell carcinoma (SCC). The most useful histopathological features for diagnosis were scalloped profile, epidermal spikes, hypergranulosis, and hyperpigmentation. L1 immunolabeling was present in 14 of 16 cases (87%). Sequencing revealed that 10 of 16 cases were associated with CPV-9 (71%), 2 cases were associated with CPV-4 (14%), and 2 cases were associated with CPV-8 (14%). In conclusion, this represents a large cohort study on canine PVPs reporting data on clinicopathological features, therapy, outcome, and the type of CPV involved for the first time in Italy.

Changes in Lymphocyte Subpopulations after Remdesivir Therapy for COVID-19: A Brief Report.

Remdesivir (RDV) has demonstrated clinical benefit in hospitalized COronaVIrus Disease (COVID)-19 patients. The objective of this brief report was to assess a possible correlation between RDV therapy and the variation in lymphocyte subpopulations. We retrospectively studied 43 hospitalized COVID-19 patients: 30 men and 13 women (mean age 69.3 ± 15 years); 9/43 had received RDV therapy. Six patients had no need for oxygen (severity group 0); 22 were on oxygen treatment with a fraction of inspired oxygen (FiO2) ≤ 50% (group 1); 7 on not-invasive ventilation (group 2); 3 on invasive mechanical ventilation (group 3); and 5 had died (group 4). Cytofluorimetric assessment of lymphocyte subpopulations showed substantial changes after RDV therapy: B lymphocytes and plasmablasts were significantly increased (p = 0.002 and p = 0.08, respectively). Cytotoxic T lymphocytes showed a robust reduction (p = 0.008). No changes were observed in CD4+-T cells and natural killers (NKs). There was a significant reduction in regulatory T cells (Tregs) (p = 0.02) and a significant increase in circulating monocytes (p = 0.03). Stratifying by disease severity, after RDV therapy, patients with severity 0-2 had significantly higher B lymphocyte and monocyte counts and lower memory and effector cytotoxic T cell counts. Instead, patients with severity 3-4 had significantly higher plasmablast and lower memory T cell counts. No significant differences for CD4+-T cells, Tregs, and NKs were observed. Our brief report showed substantial changes in the lymphocyte subpopulations analyzed between patients who did not receive RDV therapy and those after RDV treatment. Despite the small sample size, due to the retrospective nature of this brief report, the substantial changes in lymphocyte subpopulations reported could lead to speculation on the role of RDV treatment both on immune responses against the virus and on the possible downregulation of the cytokine storm observed in patients with more severe disease.

Effectiveness of SARS-CoV-2 Vaccines for Short- and Long-Term Immunity: A General Overview for the Pandemic Contrast.

BACKGROUND: The recent COVID-19 pandemic produced a significant increase in cases and an emergency state was induced worldwide. The current knowledge about the COVID-19 disease concerning diagnoses, patient tracking, the treatment protocol, and vaccines provides a consistent contribution for the primary prevention of the viral infection and decreasing the severity of the SARS-CoV-2 disease. The aim of the present investigation was to produce a general overview about the current findings for the COVID-19 disease, SARS-CoV-2 interaction mechanisms with the host, therapies and vaccines' immunization findings. METHODS: A literature overview was produced in order to evaluate the state-of-art in SARS-CoV-2 diagnoses, prognoses, therapies, and prevention. RESULTS: Concerning to the interaction mechanisms with the host, the virus binds to target with its Spike proteins on its surface and uses it as an anchor. The Spike protein targets the ACE2 cell receptor and enters into the cells by using a special enzyme (TMPRSS2). Once the virion is quietly accommodated, it releases its RNA. Proteins and RNA are used in the Golgi apparatus to produce more viruses that are released. Concerning the therapies, different protocols have been developed in observance of the disease severity and comorbidity with a consistent reduction in the mortality rate. Currently, different vaccines are currently in phase IV but a remarkable difference in efficiency has been detected concerning the more recent SARS-CoV-2 variants. CONCLUSIONS: Among the many questions in this pandemic state, the one that recurs most is knowing why some people become more seriously ill than others who instead contract the infection as if it was a trivial flu. More studies are necessary to investigate the efficiency of the treatment protocols and vaccines for the more recent detected SARS-CoV-2 variant.

Evaluation of Ki-67 expression in feline non-ocular melanocytic tumours.

BACKGROUND: Melanomas are rare in cats. The eye is the most commonly involved site, whereas few data are available about feline non-ocular melanomas (NOMs). Ki-67 thresholds with prognostic relevance have been established for canine melanomas, but not in cats. This study was undertaken to investigate the relationship between Ki-67 index, tumour characteristics, and clinical outcome in feline NOMs. Histologic samples were retrospectively reviewed. Amelanotic tumours were admitted upon immunohistochemical positivity for Melan A or S100. Evaluated parameters included morphological diagnosis, histotype, junctional activity, degree of pigmentation, vascular invasion, lymphocytic infiltrate, necrosis, mitotic count (MC) and Ki-67 index. Pigmented tumours were bleached before evaluation. Clinical and follow-up information were retrieved via telephone interviews with the referring veterinarians. RESULTS: Fifty tumours located in skin (n = 33) and mucosae (n = 17) were included. Forty-eight percent and 95% of amelanotic tumours (n = 21) stained positive for Melan A and S100, respectively. Most achromic tumours were mucosal (P < 0.001, Fisher's exact test) and presented a spindle cell morphology (P = 0.002; Fisher's exact test). MC and Ki-67 index were significantly correlated (P < 0.001; R = 0.67; Spearman's rank correlation); median values were 15 (range, 0-153) and 28% (range, 1-78%), respectively. Both were significantly higher in spindle cell melanomas, in tumours lacking junctional activity and in poorly-pigmented tumours. Follow-up information was available for 33 cats (66%). Variables related with a poor clinical outcome included mucosal location, tumour size, spindle, balloon and signet ring cell histotypes, low pigmentation, MC > 5, Ki-67 > 20% and lack of treatment administration. On multivariable analysis, only tumour histotype and treatment retained prognostic significance. CONCLUSIONS: Although the majority of feline NOMs behave aggressively, Ki-67 index, together with other parameters, may contribute to prognostic assessment. Prospective studies on homogeneous populations are warranted to identify reliable threshold values for this marker.

Observational prospective study on Lactobacillus plantarum P 17630 in the prevention of vaginal infections, during and after systemic antibiotic therapy or in women with recurrent vaginal or genitourinary infections.

We performed a prospective cohort parallel observational study on the use of Lactobacillus plantarum P 17630 in the prevention of vaginal infections. Eligible were women with a diagnosis of bacterial vaginosis (<15 days) and documented history of recurrent vaginal infections; and/or cystitis (<15 days); and/or treatment with antibiotics for bacterial respiratory tract infections during the week before the study entry. Study subjects were prescribed Lactobacillus plantarum P 17630 > 100.000.000 UFC one vaginal capsule per day for 6 days, then a capsule per week for 16 weeks. Eligible subjects were enrolled in two parallel cohorts: 85 women using (group A) and 39 not using (group B) Lactobacillus plantarum P 17630. The risk of recurrent infection within 4 months from the study entry, was higher among untreated women: multivariate OR 2.6 (95%CI 0.7-9.4). The modification of presence/intensity or symptoms was significant in both the study groups (p < .001). Impact statement What is already known on this subject? The Lactobacillus plantarum P 17630 has been shown to be active in the treatment of bacterial vaginosis and vaginal candidiasis. No data are available on its efficacy in the prevention of recurrent vaginal or urological infection or as a prevention strategy during systemic treatment with antibiotics. What do the results of this study add? This observational study suggests that Lactobacillus plantarum given for 4 months may lower the risk of recurrent infection in women with recurrent vaginal or genitourinary infection or after antibiotic systemic treatment for bacterial respiratory tract infection. The finding, however, is not statistically significant, possibly due to the lower than expected rate of infection observed in our population and consequently the limited power of the study. What are the implications of these findings for clinical practice and/or further research? New studies are needed in order to evaluate in different populations the role of Lactobacillus plantarum in lowering the risk of recurrent infection in a high-risk populations.

Response to eribulin in a difficult-to-treat, heavily pretreated breast cancer patient: a case report.

In this short paper, we report our experience with eribulin mesylate in a heavily pretreated breast cancer patient with multiple bone metastases. The patient had been treated with doxorubicin, cyclophosphamide, methotrexate, fluorouracil, tamoxifen, letrozole, LH-RH analogs, fulvestrant, bevacizumab and paclitaxel and liposomal doxorubicin. In November 2013 treatment with eribulin ready to use solution (1.23 mg/m(2) days 1 and 8 of a 21-day cycle) was started and administered for a total of 14 courses. After six cycles of eribulin, evaluation with MRI showed a marked decrease in neoplastic involvement and replacement of osteolytic lesions with osteoblastic ones. No unexpected acute toxicity was observed. Although with all the limitations of any anecdotal report, our experience documents the efficacy and safety of eribulin in this difficult-to-treat patient who had been treated with multiple lines of chemotherapy.

Peculiarity of Autoimmune Hepatitis Triggered by SARS-CoV-2 Infection.

Introduction: Recently, medical interest has been growing in SARS-CoV-2 infection and its multiorgan involvement, including the liver. Up until now, a few reports have described autoimmune hepatitis (AIH) triggered by SARS-CoV-2 infection, but no data are available about the specific liver inflammatory infiltrate and cluster of differentiation. We report a case of AIH triggered by SARS-CoV-2 infection, with a particular focus on its histological and mainly immunohistochemical features. Case description: A 60-year-old man, with a history of paucisymptomatic SARS-CoV-2 infection that occurred one month earlier, was admitted for alterations of hepatocellular necrosis and cholestasis indexes. He completed vaccination for SARS-CoV-2 a year earlier. The serologies for hepatotropic viruses were negative. The anti- smooth muscle antibodies (ASMA) and antinuclear antibodies (ANA) results were positive. Anti-liver kidney microsome (anti-LKM) antibodies and antimitochondrial (AMA) were negative. By liver biopsy, haematoxylin-eosin staining highlighted severe portal inflammation with a rich CD38+ plasma cell component, while immunohistochemical staining showed low cell CD4+ count and prevalence of CD8+ and CD3+. After biopsy, the patient started an immunosuppressant regimen, with benefit. Discussion: We can conclude that the patient developed a type 1 AIH triggered by SARS-CoV-2 infection. The presence of CD8 T-cells at immunohistochemical examination suggests different mechanisms from classic AIH. Similar cases are described after AIH triggered by SARS-CoV-2 vaccination. Conclusion: The AIH after SARS-CoV-2 infection developed by the patient showed a histological picture similar to a classic AIH for the abundant presence of plasma cells, and immunohistochemical features similar to those described after SARS-CoV-2-vaccination. LEARNING POINTS: Recently, medical interest has been growing in SARS-CoV-2 infection and its multiorgan involvement, including the liver. Underlying mechanisms are not still clear, more likely consisting of an inflammatory and immune mediated process rather than a direct cytopathic damage.Our report describes a rare case of type 1 AIH triggered by SARS-CoV-2 infection, showing a peculiar histological pattern, different from classic AIH, conversely similar to AIH triggered by SARS-CoV-2 vaccination.The mechanisms underlying liver involvement in SARS-CoV-2 infection are still under investigation. Further studies should be encouraged to improve understanding on this focus and to support physicians in its management.

The diagnostic relevance of mesenteric lymph node biopsy in small intestinal lymphoma in cats.

BACKGROUND: Regional lymph nodes are frequently sampled in cats with suspected intestinal lymphoma; however, their diagnostic value has not been explored. OBJECTIVES: To investigate whether histologic and immunohistochemical analysis of mesenteric lymph nodes correlates with the diagnosis of intestinal lymphoma in cats. ANIMALS: One hundred 2 client-owned cats diagnosed with intestinal lymphoma. METHODS: Retrospective study. The inclusion criteria required a full-thickness biopsy of the small intestine and concurrent excision of mesenteric lymph nodes. Histologic and immunophenotypic analyses were performed on intestinal biopsies and corresponding lymph nodes. Selected nodal samples diagnosed with reactive lymph nodes underwent clonality testing. RESULTS: Transmural T-cell lymphomas, encompassing small and large cell types, were predominant (64 cases, 62.7%), with large B-cell lymphomas being more frequently transmural (68.8%) than mucosal (31.2%). Among all lymph nodes examined, 44 (43.1%; 95% CI: 33.9%-52.8%) exhibited neoplastic infiltration. Among cases of small cell lymphoma, 51 out of 72 (70.8%; 95% CI: 59.4%-80.1%) showed no nodal involvement. Clonality results correctly identified 19/30 (63.3%; 95% CI: 45.5%-78.2%) reactive lymph nodes. Concerns were raised regarding clonal identification in the remaining cases and potential misdiagnoses based on phenotypic characteristics. CONCLUSION AND CLINICAL IMPORTANCE: The study underscores the potential drawbacks of relying solely on mesenteric lymph nodes for diagnosing intestinal lymphomas in cats, particularly small cell subtypes. It emphasizes the importance of full-thickness biopsies for assessing transmural infiltration and recommends caution when utilizing mesenteric lymph nodes for histologic, immunohistochemical and clonality evaluations in mucosal lymphomas. Despite limitations, this research highlights the need for comprehensive diagnostic strategies in cats with intestinal lymphoma.

Alterations in thyroid function among the different polycystic ovary syndrome phenotypes.

The study evaluates the prevalence of subclinical thyroid dysfunction in infertile PCOS patients, according to the different PCOS phenotypes and to examine whether insulin sensitizers in insulin resistant (IR) PCOS patients may improve thyroid function. The study population consisted of all PCOS patients, attending the infertility and IVF unit of Department of Pediatrics, Obstetrics and Reproductive Medicine of University of Siena, Italy, and compared them to regularly cycling, healthy, infertile controls. Upon admission, blood was drawn from all patients during the early follicular phase, for complete hormonal and metabolic profiles. In IR-PCOS patients treated with insulin sensitizers, blood was drawn again after 6 months. PCOS patients had a significantly higher prevalence of subclinical thyroid dysfunction compared to infertile controls. While no significant association was detected between TSH value and the presence of hyperandrogenism, overweight and obese PCOS patients, as well as IR PCOS patients showed significantly higher prevalence of subclinical thyroid dysfunction. Moreover, among IR PCOS patients, 6 months treatment with insulin sensitizers significantly reduces TSH levels. Infertile PCOS patients have a high prevalence of subclinical thyroid dysfunction, which may be successfully treated in IR PCOS patients by insulin sensitizers.

Robot-Assisted versus Laparoscopic Gastrointestinal Surgery: A Systematic Review and Metanalysis of Intra- and Post-Operative Complications.

BACKGROUND: The use of robotic surgery is attracting ever-growing interest for its potential advantages such as small incisions, fine movements, and magnification of the operating field. Only a few randomized controlled trials (RCTs) have explored the differences in perioperative outcomes between the two approaches. METHODS: We screened the main online databases from inception to May 2023. We included studies in English enrolling adult patients undergoing elective gastrointestinal surgery. We used the following exclusion criteria: surgery with the involvement of thoracic esophagus, and patients affected by severe heart, pulmonary and end-stage renal disease. We compared intra- and post-operative complications, length of hospitalization, and costs between laparoscopic and robotic approaches. RESULTS: A total of 18 RCTs were included. We found no differences in the rate of anastomotic leakage, cardiovascular complications, estimated blood loss, readmission, deep vein thrombosis, length of hospitalization, mortality, and post-operative pain between robotic and laparoscopic surgery; post-operative pneumonia was less frequent in the robotic approach. The conversion to open surgery was less frequent in the robotic approach, which was characterized by shorter time to first flatus but higher operative time and costs. CONCLUSIONS: The robotic gastrointestinal surgery has some advantages compared to the laparoscopic technique such as lower conversion rate, faster recovery of bowel movement, but it has higher economic costs.

Current Evidence on Vaccinations in Pediatric and Adult Patients with Systemic Autoinflammatory Diseases.

Systemic autoinflammatory diseases (SAIDs) are defined by recurrent febrile attacks associated with protean manifestations involving joints, the gastrointestinal tract, skin, and the central nervous system, combined with elevated inflammatory markers, and are caused by a dysregulation of the innate immune system. From a clinical standpoint, the most known SAIDs are familial Mediterranean fever (FMF); cryopyrin-associated periodic syndrome (CAPS); mevalonate kinase deficiency (MKD); and periodic fever, aphthosis, pharyngitis, and adenitis (PFAPA) syndrome. Current guidelines recommend the regular sequential administration of vaccines for all individuals with SAIDs. However, these patients have a much lower vaccination coverage rates in 'real-world' epidemiological studies than the general population. The main purpose of this review was to evaluate the scientific evidence available on both the efficacy and safety of vaccines in patients with SAIDs. From this analysis, neither serious adverse effects nor poorer antibody responses have been observed after vaccination in patients with SAIDs on treatment with biologic agents. More specifically, no new-onset immune-mediated complications have been observed following immunizations. Post-vaccination acute flares were significantly less frequent in FMF patients treated with colchicine alone than in those treated with both colchicine and canakinumab. Conversely, a decreased risk of SARS-CoV-2 infection has been proved for patients with FMF after vaccination with the mRNA-based BNT162b2 vaccine. Canakinumab did not appear to affect the ability to produce antibodies against non-live vaccines in patients with CAPS, especially if administered with a time lag from the vaccination. On the other hand, our analysis has shown that immunization against Streptococcus pneumoniae, specifically with the pneumococcal polysaccharide vaccine, was associated with a higher incidence of adverse reactions in CAPS patients. In addition, disease flares might be elicited by vaccinations in children with MKD, though no adverse events have been noted despite concurrent treatment with either anakinra or canakinumab. PFAPA patients seem to be less responsive to measles, mumps, and rubella-vaccine, but have shown higher antibody response than healthy controls following vaccination against hepatitis A. In consideration of the clinical frailty of both children and adults with SAIDs, all vaccinations remain 'highly' recommended in this category of patients despite the paucity of data available.

Type 1 citrullinemia patient with Brugada pattern undergoing general anesthesia for dental extractions: A case report.

Key Clinical Message: The perioperative control of ammonia, reduction of stress, and administration of drugs tolerated in type 1 citrullinemia and Brugada pattern allowed the successful and uneventful management of general anesthesia in the study patient. Abstract: The aim of this study was to report the targeted perioperative management of general anesthesia (GA) adopted for dental extractions in a rare patient with type 1 citrullinemia and Brugada pattern. A male, Caucasian, adult type 1 citrullinemia patient needed dental extractions under GA. The medical history showed neurodevelopmental impairment, growth retardation, epilepsy, and a Type 2 Brugada electrocardiographic pattern in the second precordial lead. The authors focused the anesthesiologic protocol on the prevention of hyperammonemia and fatal arrhythmias. Changes in diet and 10% glucose solution administration prevented protein catabolism due to the fasting period (ammonia was 44 µmol/L preoperatively and 46 µmol/L postoperatively; glycemia was 120 g/dL preoperatively and 153 g/dL postoperatively). The patient received a continuous electrocardiogram, noninvasive blood pressure, pulse oximeter, entropy monitoring, train-of-four monitoring, and external biphasic defibrillator pads. Midazolam, remifentanil, and dexamethasone were administered for pre-anesthesia; thiopental and rocuronium for induction; remifentanil and desflurane for maintenance; sugammadex for decurarization. After the intraligamentary injection of lidocaine 2% with epinephrine 1:100,000 for local anesthesia, the patient developed a transient Type 1 Brugada pattern that lasted a few minutes. The whole procedure lasted 30 min. The patient's discharge to ward occurred 3 h after the end of GA. The perioperative management of ammonia, reduction of stress, and administration of drugs tolerated in Type 1 citrullinemia and Brugada pattern allowed the successful and uneventful administration of GA in the study patient.

Effect of COVID-19 Vaccination on the In-Hospital Prognosis of Patients Admitted during Delta and Omicron Waves in Italy.

All-cause mortality related to the SARS-CoV-2 infection has declined from the first wave to subsequent waves, probably through vaccination programs and the availability of effective antiviral therapies. Our study aimed to evaluate the impact of the SARS-CoV-2 vaccination on the prognosis of infected patients. Overall, we enrolled 545 subjects during the Delta variant wave and 276 ones during the Omicron variant wave. Data were collected concerning vaccination status, clinical parameters, comorbidities, lung involvement, laboratory parameters, and pharmacological treatment. Outcomes were admission to the intensive care unit (ICU) and 30-day all-cause mortality. Overall, the final sample included 821 patients with a mean age of 62 ± 18 years [range 18-100], and 59% were men. Vaccinated patients during the Delta wave were 37% (over ¾ with two doses), while during the Omicron wave they were 57%. Vaccinated patients were older (68 vs. 57 years), and 62% had at least one comorbidity Admission to the ICU was 20%, and the mortality rate at 30 days was 14%. ICU admissions were significantly higher during the Delta wave than during Omicron (OR 1.9, 95% CI 1.2-3.1), while all-cause mortality did not differ. Unvaccinated patients had a higher risk of ICU admission (OR 2.0, 95% CI 1.3-3.1) and 30-day all-cause mortality (OR 1.7, 95% CI 1.3-2.7). Results were consistent for both Delta and Omicron variants. Overall, vaccination with at least two doses was associated with a reduced need for ICU admission. Even one shot of the vaccine was associated with a significantly reduced 30-day mortality.

Stereotactic radiation therapy for oligometastatic esophagogastric adenocarcinoma: outcome and prognostic factors.

OBJECTIVE: The aim of this study was to evaluate clinical results and prognostic factors in a cohort of patient with oligometastatic esophagogastric adenocarcinoma treated with stereotactic radiation therapy (SRT). METHODS: This retrospective study included patients affected by 1-3 metastases treated with SRT from 2013 to 2021. Local control (LC), overall survival (OS), progression-free survival (PFS), time to polymetastatic dissemination (TTPD) and time to systemic therapy change/initiation (TTS) were evaluated. RESULTS: Between 2013 and 2021, 55 patients were treated with SRT on 80 oligometastatic sites. Median follow-up was 20 months. Nine patients had local progression. 1 and 3 years LC was respectively 92 and 78%. 41 patients experienced further distant disease progression, median PFS was 9.6 months, 1 and 3 years PFS was respectively 40 and 15%. 34 patients died, median OS was 26.6 months, 1 and 3 years OS was respectively 78 and 40%. During follow-up, 24 patients changed or initiated a new systemic therapy; median TTS time was 9 months. 27 patients experienced poliprogression, 44% after 1 year and 52% after 3 years. Median TTPD was 8 months. The best local response (LR), tyming of metastases and PS were related with prolonged PFS on multivariate analysis. LR was correlated with OS at multivariate analysis. CONCLUSION: SRT represents a valid treatment for oligometastatic esophagogastric adenocarcinoma. CR correlated with PFS and OS, while metachronous metastasis and a good PS correlated with a better PFS. ADVANCES IN KNOWLEDGE: In selected gastroesopagheal oligometastatic patients, SRT can prolong OS Local response to SRT, metachronous timing of metastases and better PS improve PFS.Local response correlates with OS.

The impact of stereotactic ablative radiotherapy on oligoprogressive metastases from renal cell carcinoma.

BACKGROUND: Renal cell carcinoma (RCC) represents 80-90% of all kidney tumors and about 15-25% of patients will develop distant metastases. Systemic therapy represents the standard of care for metastatic patients, but stereotactic ablative radiotherapy (SABR) may play a relevant role in the oligoprogressive setting, defined as the progression of few metastases during an ongoing systemic therapy on a background of otherwise stable disease. Aim of the present study was to analyze the outcome of RCC patients treated with SABR on oligoprogressive metastases. MATERIALS AND METHODS: In this monocenter study, we analyzed patients affected by RCC treated with SABR on a maximum of 5 cranial or extracranial oligoprogressive sites of disease. Endpoints were overall survival (OS), progression-free survival (PFS), and toxicity. RESULTS: We included 74 oligoprogressions (26 intracranial and 48 extracranial) and 57 SABR treatments in 44 patients. Most common concomitant treatments were sunitinib (28, 49.1%), pazopanib (12, 21.0%) and nivolumab (11, 19.3%). Median follow-up was 19.0 months, and 1- and 2-year OS rates were 79.2% and 57.3%, respectively. Repeated SABR was a positive predictive factor for OS (p = 0.034). Median PFS was 9.8 months, with 1- and 2-year rates of 43.2% and 25.8%. At multivariable analysis, disease-free interval (p = 0.022) and number of treated metastases (p = 0.007) were significant for PFS. About 80% of patients continued the ongoing systemic therapy 1- and 2-years after SABR with no grade 3 or 4 toxicities. CONCLUSIONS: we confirmed the efficacy and safety of SABR for oligoprogression from RCC, with the potential to ablate resistant metastases and to prolong the ongoing systemic therapy.

Effect of Preoperative Music Therapy Versus Intravenous Midazolam on Anxiety, Sedation and Stress in Stomatology Surgery: A Randomized Controlled Study.

BACKGROUND: Patients undergoing surgery and general anesthesia often experience anxiety, fear and stress, with negative bodily responses. These may be managed by the pre-procedural application of anxiolytic, analgesic, and anesthetic drugs that have, however, potential risks or side effects. Music therapy (MT) can be used as a complementary no-drug intervention alongside standard surgical care before, during and after medical procedures. The aim of this study was to evaluate the effects of preoperative MT intervention compared to premedication with midazolam on levels of anxiety, sedation and stress during general anesthesia for elective stomatology surgery. METHODS: A two-arm randomized and controlled single-center, parallel-group, pre-post event study was conducted. In total, 70 patients affected by stage I or II (both clinically and instrumentally N0) micro-invasive oral cancer and undergoing elective surgery under general anesthesia were assigned to the control group (CG) or to the music therapy group (MTG). MTG patients received preoperative music therapy intervention (MT) from a certified music therapist before surgery, while the CG patients did not receive MT but instead received premedication with intravenous midazolam, 0.02 mg/kg. Anesthesia was the same in both groups. The systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) were recorded at the entrance to the operating room, just before the induction of anesthesia and every 5 min until the end of surgery. An anxiety visual analogues scale (A-VAS) was used to evaluate the level of anxiety. The bispectral index (BIS) monitor was used to measure the depth of sedation just before and 10 min after both music intervention and midazolam administration. Stress response was assessed 5 min before and 20 min after surgery via the control of plasma prolactin (PRL), growth hormone (GH), and cortisol levels. The patient global impression of satisfaction (PGIS) was tested 1 h after surgery. Participants in the MTG were asked to answer 3 questions concerning their experience with MT. RESULTS: No statistical differences among the PRL, GH and cortisol levels between the two groups were registered before and after the treatment, as well as for PAS, PAD and HR. Significant differences in the A-VAS scores between the MTG and CG (p < 0.01) was observed. Compared to the CG, MTG patients had a statistically significantly lower BIS score (p = 0.02) before induction. A PGIS score of 86.7% revealed that patients in the MTG were very satisfied, versus 80% in the CG (p < 0.05). CONCLUSION: Preoperative music therapy could be an alternative to intravenous midazolam when aiming to promote a preoperative and post-operative state of anxiolysis and sedation in stomatology surgery, even if no differences were found in terms of the surgery-related stress response according to physiological and hormonal determinations.

Total tumor volume as a predictor of survival in patients with multiple oligometastases treated with stereotactic ablative radiotherapy (SABR).

BACKGROUND: Delivering stereotactic ablative radiotherapy (SABR) in patients with multiple oligometastases represents a challenge for clinical and technical reasons. We aimed to evaluate the outcome of patients affected by multiple oligometastases treated with SABR and the impact of tumor volume on survival. MATERIALS AND METHODS: We included all the patients treated with single course SABR for 3 to 5 extracranial oligometastases. All patients were treated with the volumetric modulated arc therapy (VMAT) technique with ablative intent. End-points of the analysis were overall survival (OS), progression free survival (PFS), local control (LC) and toxicity. RESULTS: 136 patients were treated from 2012 to 2020 on 451 oligometastases. Most common primary tumor was colorectal cancer (44.1%) followed by lung cancer (11.8%). A total of 3, 4 and 5 lesions were simultaneously treated in 102 (75.0%), 26 (19.1%), and 8 (5.9%) patients, respectively. Median total tumor volume (TTV) was 19.1 cc (range 0.6-245.1). With a median follow-up of 25.0 months, OS at 1 and 3 years was 88.4% and 50.2%, respectively. Increasing TTV was independent predictive factor of worse OS (HR 2.37, 95% CI 1.18-4.78, p = 0.014) and PFS (HR 1.63, 95% CI 1.05-2.54; p = 0.028). Median OS was 80.6 months if tumor volume was ≤ 10 cc (1 and 3 years OS rate 93.6% and 77.5%, respectively), and 31.1 months if TTV was higher than 10 cc (1 and 3 years OS rate 86.7% and 42.3%, respectively). Rates of LC at 1 and 3 years were 89.3% and 76.5%. In terms of toxicity, no grade 3 or higher toxicity was reported both in the acute and late settings. CONCLUSION: We demonstrated the impact of tumor volume on survival and disease control of patients affected by multiple oligometastases treated with single course SABR.

Can STEreotactic Body Radiation Therapy (SBRT) Improve the Prognosis of Unresectable Locally Advanced Pancreatic Cancer? Long-Term Clinical Outcomes, Toxicity and Prognostic Factors on 142 Patients (STEP Study).

AIM: The gold standard of care for pancreatic adenocarcinoma is the integrated treatment of surgery and chemotherapy (ChT), but about 50% of patients present with unresectable disease. Our study evaluated the efficacy in terms of local control, survival and safety of stereotactic body radiation therapy (SBRT) in locally advanced pancreatic cancer (LAPC). METHODS: A retrospective study (STEP study) analyzed patients with LAPC treated with a dose of 45 Gy in 6 fractions. Local control (LC), distant progression free survival (DPFS), overall survival (OS) and toxicity were analyzed according to the Kaplan-Meier method. RESULTS: A total of 142 patients were evaluated. Seventy-six patients (53.5%) received induction ChT before SBRT. The median follow-up was 11 months. One-, 2- and 3-year LC rate was 81.9%, 69.1% and 58.5%. Median DPFS was 6.03 months; 1- and 2-year DPFS rate was 19.9% and 4.5%. Median OS was 11.6 months and 1-, 2- and 3-year OS rates were 45.4%, 16.1%, and 9.8%. At univariate analysis, performed by the log-rank test, age < 70 years (p = 0.037), pre-SBRT ChT (p = 0.004) and post-SBRT ChT (p = 0.019) were associated with better OS. No patients experienced G3 toxicity. CONCLUSION: SBRT represents an effective and safe therapeutic option in the multimodal treatment of patients with LAPC in terms of increased LC. When SBRT was sequentially integrated with ChT, the treatment proved to be promising in terms of OS as well.

Masculine men do not like feminine wording: The effectiveness of gendered wording in health promotion leaflets in the UK.

Following mixed-methods sequential design and drawing on the message-audience congruence concept and homophily theory, across three studies in the UK, we examined the effect of gendered wording and endorser's gender on the effectiveness of leaflets promoting walking. In Study 1, a mall-intercept study achieved 247 completed questionnaires. Results demonstrated that men and women indicated the highest behavioural intentions for communal wording presented by a male endorser. However, pairwise comparisons revealed that when the wording of the advert was agentic and the endorser was male, males indicated significantly higher scores of behavioural intentions compared with females. Attitude towards the ad for women was highest for communal wording/female endorser; for men it was for agentic wording/male endorser. In Study 2, consumers' views towards the gendered content were explored in 20 semi-structured interviews. In study 3 we examined the impact of the respondent's gender role identity on gendered content effectiveness. Overall, when controlled for level of gender role identity, only masculine males evaluated leaflets featuring communal wording negatively which suggests that wording matters only for masculine males, but not for other men and women. Theoretically, we identified that gender-based message-respondent congruence is not a necessary aspect of communications to be effective, except for one group: masculine males. Our study identified dominant gender role identity as a factor that explained respondents' preferences for presented stimuli. Specifically, males who display masculine gender role identity differ in evaluations of communal wording from all other groups. Social and commercial marketers who target men and women with exercise-related services should consider the use of agentic wording endorsed by a male endorser when targeting masculine men to increase the likelihood of eliciting positive attitudes towards the communication. However, such distinctions should not be associated with differences in women's evaluations or men who do not report masculine gender role identity.