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Background: Medical schools often lack training for serious illness conversations with patients and caregivers. We developed a curriculum in our elective Transitioning to Residency medical student course, focused on end-of-life discussions. This paper provides an overview of the curriculum and outcomes from an advanced preparation assignment and student evaluations., Methods: The curriculum included a "hands-on" skills session delivered via Zoom. Small groups of students (3-4) assumed roles on an interprofessional team (Intensivist, cardiologist, nurse, social worker). They met with two adult children, played by palliative/geriatric clinical staff, of a 79-year-old patient with a complex cardiac history and on ventilator support to address: (1) the patient's status, (2) goals of care, and (3) withdrawal of ventilator support. Using a flipped classroom format, students reviewed the case, role assignments, a family meeting webinar, and other materials in advance. They completed a survey reflecting on the upcoming family meeting. Afterwards, students evaluated the session., Results: Eighty students (19.6%) participated in 2021 and 2022. The reflection survey shows students agreed the patient's prognosis was poor and decision-making should be shared. They anticipated difficulty accepting prognosis, discordance between family members and/or the team, and challenging emotions. Results show a difference between the anticipated roles of the assigned physicians compared to the other disciplines. Post-session evaluations ranged from 4.7 to 4.9/5 (1 = strongly disagree, 5 = strongly agree)., Conclusion: The pre-session reflection helped students prepare for their roles. The training was well received, and we hope it prepares students to take on serious illness discussions during residency., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

In the present study a comprehensive protocol to assess chewing in four children with Down syndrome is provided and described. One baseline and four assessment meals were conducted across four textures of foods to investigate the presence or absence of components of chewing (bite down, chew and tongue lateralization), as well as movements associated with the development of chewing. Results showed that at baseline all participants ate their typical diet (i.e., pureed food) but no chewing components or movements were observed. The findings of the assessment protocol indicated that it offers a prescriptive assessment of chewing and its components across different food textures. The results of the assessment provided useful information for clinicians by identifying a potential starting point for interventions to address chewing deficits. Furthermore, the findings add to the existing literature on the role of tongue lateralization and specific tongue movements in chewing. Implications of the findings for chewing interventions and future research are discussed.

Introduction: Adenoid cystic carcinomas (ACCs) account for 10% of all malignant salivary tumours. They are slow-growing but locally aggressive. Reports of liver and renal metastases are rare., Case Description: A 58-year-old woman who had undergone resection of a left submandibular ACC in 1995 was referred to our centre for follow-up in 2018. A computed tomography scan revealed two lesions: one on segment six of the liver and the other on a kidney. A hepatic wedge resection and right nephrectomy were performed. The postoperative course was uneventful. At 2-year follow-up, the patient was alive and well with no evidence of disease., Conclusion: Management of ACC is a therapeutic challenge because of its tendency for distant metastases. The literature recommends regular follow-up imaging and radical surgical treatment but specific guidelines for the approach to recurrence are lacking.

Objective: We evaluated the impact of an experiential learning strategy on both the adherence to the use of bundles and the incidence of ventilator-associated pneumonia in critically ill adult patients., Methods: Longitudinal, quasi-experimental interrupted time-series study in a tertiary teaching hospital in Buenos Aires, Argentina. Successive measurements were made before and after the intervention was implemented between January 2016 and December 2018. Our main exposure was experiential learning, which was based on a combination of play activities, simulation models, knowledge and attitude competencies, role-playing and feedback. The adherence to the bundle for the care of mechanically ventilated critically-ill adult patients and the occurrence of ventilator-associated pneumonia were the main outcomes of interest. We used generalized linear models including time as a linear spline to estimate the effect of the experiential learning strategy both on the adherence to the bundle of care and the occurrence of ventilator-associated pneumonia during long-term follow-up., Results: The overall proportion of adequate bundle use before and after the implementation of the intervention was 60.8% (95% CI: 56.9-64.7) and 85.6% (95% CI: 81.2-90.1), respectively. The incidence rate of ventilator-associated pneumonia before and after the intervention was 6.11 (95% CI: 5.82-6.40) and 3.55 (95% CI: 2.96-4.14) every 1000 days of mechanical ventilation, respectively. The estimated baseline monthly change in the adherence to the mechanical ventilation bundle was 0.4% (95%CI: -0.3-1.2%, p  = 0.31) and 1.1% (95% CI: 0.2-2.2%, p  < 0.01) before and after the implementation of the intervention, respectively. These results were consistent across our statistical quality control analysis., Conclusions: The implementation of experiential learning strategies improves the adherence to bundles in the care of mechanically ventilated critically ill adult patients. Such strategies also decrease the incidence rate of ventilator-associated pneumonia. Both effects appear to remain constant during long-term follow-up., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Intensive Care Society 2019.)

Purpose: Patients with Ewing sarcoma who are 40 years old or older are usually excluded from clinical trials. For this reason, information on this subset of patients is limited., Methods: Clinical characteristics and treatment-related variables of patients aged 40 years or more, with a diagnosis of Ewing sarcoma, treated at the authors' institution had been prospectively collected since 1999., Results: Thirty-one patients were identified, with ages ranging from 40 to 70 years (median 45 years). Twenty-six (84%) had localized disease, 4 patients presented with lung metastases, and 1 patient had multiple metastases (bone, lung, abdominal nodes, and bone marrow). The primary tumors were skeletal in 19 (61%) patients, while 12 (39%) had extraskeletal disease. All patients received chemotherapy according to regimens similar to those adopted in younger patients, based on doxorubicin, cyclophosphamide, etoposide, vincristine, dactinomycin, and ifosfamide. All patients experienced grade 4 leukopenia (100%); red blood cells or platelets transfusions were needed in 50% and 16% of patients, respectively. Toxicity-related dose reduction was required in 13 patients (43%). The 5-year overall survival (OS) was 54% for the whole group. In patients with complete remission, 5-year disease-free survival was 57%. Survival was different for patients with skeletal and extraskeletal Ewing sarcoma (5-year OS: 64% vs 40%, p = 0.2)., Conclusions: In older patients, the incidence of extraskeletal Ewing sarcoma is high. Intensive chemotherapy treatment can be recommended in this group. The high chemotherapy toxicity can be justified by expected results, similar to those of younger patients.

Background: The development of thyroid antibodies and the alteration of thyroid function are the most common disorders associated with interferon alfa therapy in individuals with chronic hepatitis C (CHC).In this study, we compared the course of Graves disease (GD) between patients diagnosed with CHC and treated with interferon alfa and uninfected patients., Methods: We retrospectively analyzed data from 39 GD patients (15 men and 24 women, group 1) affected by CHC and treated with interferon alfa and from 43 uninfected GD patients (19 men and 24 women, group 2) who were seen at our institution from 1999 to 2011. All GD patients were treated with methimazole (MMI). Daily dose of MMI, duration of MMI therapy, and remission rate were evaluated in both groups., Results: The daily dose of MMI was found to be lower in group 1 as compared with group 2 (9.74 ± 5.94 mg/d vs 14.12 ± 8.64 mg/d in group 1 vs group 2, respectively, P < 0.01). In addition, the duration of MMI treatment was found to be lower in group 1 as compared with group 2 (13.98 ± 13.0 months vs 38.86 ± 27.13 months in group 1 vs group 2, respectively; P < 0.01). The remission rate from GD was higher in the patients of group 1 in comparison with the patients of group 2 (87.17 % vs 48.86% in group 1 vs group 2, respectively, P < 0.005)., Conclusion: Altogether, our data demonstrate a more favorable course of GD in the patients with CHC treated with interferon alfa compared with GD occurring in the patients without CHC.

Aims and Background: Information is scarce on systemic treatment of pelvic osteosarcoma because most chemotherapy protocols for osteosarcoma include patients with extremity tumors and aged up to 30-40 years., Methods: Data on patients <41 years of age with high-grade pelvic osteosarcoma were prospectively collected. Patients received two chemotherapy protocols consisting of methotrexate, cisplatin, doxorubicin (MAP) and standard-dose or high-dose ifosfamide., Results: Forty patients between 11 and 36 years were included. The most frequent histological subtype was osteoblastic followed by chondroblastic (37.5%). Complete surgical remission was achieved in 65% of patients. Eighteen patients had MAP/standard-dose ifosfamide, 22 MAP/high-dose ifosfamide. Primary chemotherapy was given to 25 patients and 6 (24%) of them had a good histological response. Median follow-up was 32 months (range, 4-134). Five-year overall survival was 27.5%: 33% in localized and 0 in metastatic patients ( P = 0.02); 45% in patients with complete surgical remission and 0 for patients without complete surgical remission (P = 0.001). Local recurrence rate was 46%. In patients with complete surgical remission, 5-year overall survival was 32% with MAP/standard-dose ifosfamide and 59% with MAP/high-dose ifosfamide regimen (P = 0.3)., Conclusions: Local control is the major issue in the treatment of pelvic osteosarcoma. Poor pathological response and high incidence of chondroblastic variant indicate different characteristics between pelvic and extremity osteosarcoma. Chemotherapy with MAP and high-dose ifosfamide might be beneficial in patients with pelvic osteosarcoma and warrants further investigation.

HBV is a hepatotropic and non-cytopathic virus that causes more than one million deaths annually from liver cirrhosis and hepatocellular carcinoma. As the virus itself is non-cytopathic, it is widely accepted that both viral control and liver pathology are mediated by the host immune system. Until recently, the focus has been on the crucial role of adaptive immune responses in controlling HBV infection, but the potential contribution of the innate system is now an important area of controversy. Unanswered questions include whether and when HBV can trigger components of innate immunity, and whether HBV can actively suppress the induction of innate immunity. We discuss the data available from animal models and human HBV infection addressing the role of innate immunity in the first part of this review. In the second part, we address the immunopathogenesis of the inflammatory events that characterize chronic hepatitis B. The mechanisms thought to be responsible for liver inflammation, namely the intrahepatic recruitment of inflammatory cells, which is orchestrated by chemokines, have been described; however, the underlying immunological triggers are much less clear. The prevailing idea is that liver inflammation results from a recovery of HBV-specific T-cells directly causing liver injury, but this scenario is supported by scanty experimental data. By contrast, recent findings raise the possibility of a contribution from innate components, such as natural killer cells.

An association between Graves' disease (GD) and chronic hepatitis C (C-HC) has been observed both in the presence and the absence of recombinant interferon-alpha (rIFN-alpha) treatment. rIFN-alpha-induced GD is characterized by suppressed thyroid-stimulating hormone levels; normal or elevated free triiodothyronine (FT3) and free thyroxine (FT4) values; the presence of thyroid peroxidase antibodies, antithyroglobulin antibodies, and thyroid receptor antibodies; and high iodine thyroid uptake. In contrast, GD developed during C-HC without rIFN-alpha is less clearly defined. In this study, we examined two groups of patients: group A, 28 patients with C-HC treated with rIFN-alpha who developed GD after 1 to 9 months, and group B, 10 patients with C-HC who developed GD without a previous rIFN-alpha treatment. At the time of GD, both groups started methimazole therapy; thyroid function was reevaluated after 3, 6, 9, and 12 months. Group A patients continued IFN. After 12 months, all patients of group A were euthyroid, and 21 of them (75%) had already stopped methimazole treatment, whereas all patients of group B were euthyroid and only 2 (20%) had stopped methimazole. In conclusion, the data show a better course of GD, with a more precocious and significantly higher number of recoveries in patients with rIFN-alpha-induced GD than in rIFN-alpha-unrelated disease. Further studies are needed to establish whether the two types of GD differ not only from a clinical point of view but also because of different underlying pathogenetic mechanisms.

Aims and Background: Ewing's sarcoma is a highly malignant musculoskeletal tumor composed of small round cells. Although important results have been achieved with surgery associated with chemotherapy, recurrent disease is still a major problem. In order to define new prognostic factors useful for therapeutic decision-making, we conducted a study on 38 Ewing's sarcoma samples in which c-myc oncogene expression and Ki67 proliferation index were correlated with clinical outcome., Methods and Study Design: Nineteen patients developed metastases during follow-up and 10 of these patients died. C-myc and Ki67 protein expression was evaluated by immunohistochemistry performed on 5 microm formalin-fixed and paraffin-embedded sections, while the c-myc mRNA transcript was localized using in situ hybridization., Results: A statistically positive correlation was found between c-myc protein and Ki67 (P = 0.001) and c-myc mRNA and Ki67 expression (P = 0.047). The 38 patients were divided into two groups using as the cutoff 50% of Ki67-positive cells. The disease-free survival and overall survival estimates were 68% and 90%, respectively, in the group of patients with a percentage of Ki67-positive cells <50%, and 25% and 50%, respectively, in the group with a percentage of Ki67-positive cells > or = 50%. The difference between the survival curves was statistically significant (P <0.05 and P <0.01). Furthermore, relapsed patients had a high and uniform expression of c-myc protein and mRNA compared to disease-free patients., Conclusion: These results suggest a possible role of the c-myc oncogene and Ki67 antigen in the malignant progression of Ewing's sarcoma.

Aims and Background: Forty-four bone hemangioendotheliomas (HEs) of different histological grades were studied to evaluate the expression and distribution of laminin, type IV collagen, cathepsin G and cathepsin D in cell differentiation and malignancy., Results: In poorly-differentiated HEs the discontinuous distribution of laminin and type IV collagen around angioblastic cords, tubes and cavities revealed an irregular and disorganized basement membrane (BM) architecture corresponding to an increased cell proliferation and secretion of cathepsin D and cathepsin G by tumor cells., Conclusions: The mean nucleolar organizer region (NOR) area, as a measure of cell proliferation, was significantly higher in grade 4 malignancies than in lower grades, revealing novel prognostic parameters.

We describe a new formulation for a hydrophilic resin, mostly composed of glycol methacrylate and hydroxypropyl methacrylate and here referred to as bioacryl, that allows the performance of morphological and immunohistochemical investigations at both light and electron microscopic levels. Immunolocalizations performed on bioacryl-embedded tissues are characterized by high specificity with virtually absent background staining. Finally, the new resin yields satisfactory fine-structural preservation, resulting in ultrastructural images of better quality than those obtained with Lowicryl K4M.

A peroxidase-colloidal gold double labeling system in immunoelectron microscopy was used to investigate the ultrastructural features of human large granular lymphocytes (LGL) subpopulations. Three subsets of LGL, Leu-7+-Leu-11-, Leu-7+-Leu-11+, Leu-7- -Leu-11+, were characterized using combinations of the monoclonal antibodies anti-Leu-7 and anti-Leu-11. They showed different ultrastructural patterns. In fact, Leu-7+-Leu-11- cells showed a high nuclear/cytoplasmic ratio (N/C), a round nucleus, a cytoplasm with few organelles, and a rather even surface. Moreover, most of them lacked electron-dense granules. On the other hand, Leu-11+ cells displayed a low N/C, an irregular-shaped nucleus, and a cytoplasm containing a well-developed Golgi apparatus, many mitochondria, vacuoles, vesicles, and numerous electron-dense granules. Moreover, they exhibited an irregular cell surface. Thus, Leu-7+-Leu-11- cells seemed to represent an immature form of LGL, while cells expressing the Leu-11 antigen showed a fine structure specific for functional NK cells. Our findings suggest that the expression of HNK-1 (Leu-7) and Leu-11 antigens respectively represents subsequent stages in NK cell differentiation.

This is a report on a case of 2 concurrent neoplasms of different histology within the same kidney: a renal cell carcinoma and a transitional cell carcinoma of the renal pelvis in a patient affected by chronic renal failure due to abuse of phenacetin. There was also a transitional cell carcinoma of the urinary bladder.