The finding of corpse parts poses several challenges for the forensic pathologist presenting implications for identification, diagnosis of death and determination of wounds vitality. Further interpretative difficulties in cases of cadaveric dismemberment derive from the scarcity of tanatochronological parameters useful to estimate the post-mortem interval (PMI) and the absence of uniform investigative protocols in the different centres of forensic pathology. The present study proposes an investigation protocol for the cadaveric dismemberment through the discussion of a case series. The study group consisted of cases in which the dismemberment was performed after the murder. For all cases, a study protocol based on crime scene investigation, post-mortem computed tomography (PMCT), autopsy, toxicological, histological, immunohistochemical and genetic investigations was implemented. In particular, the standardised use of radiographic study before the autopsy allows all to have information that can guide the forensic pathologist during the autopsy. The use of immunohistochemistry allows an assessment of the vitality of the lesions possibly involved in the determinism of death, as well as of the surfaces of dismemberment, representing a tool of considerable utility for forensic purposes. The genetic investigations allow the identification of the victims, while the toxicological ones highlight the possible abuse of substances. The implemented protocol presents a demonstrated usefulness in improving diagnostic accuracy in corpse dismemberment cases.

Merkel cell carcinoma (MCC) is a rare aggressive form of skin cancer originating in neuroendocrine cells. The antiprogrammed death ligand 1 (PD-L1) monoclonal antibody (mAb) avelumab has been approved for treatment of MCC, but options are limited, should it be ineffective as a monotherapy. Combined therapy with low/moderate dose nab-paclitaxel and an interleukin 15 (IL-15)-based therapeutic such as the IL-15 \'superagonist\' N-803 may increase response by activation of the immune system. The case of a 71-year-old man diagnosed with MCC who achieved and maintained a complete response (CR) by treatment with the anti-PD-L1 mAb avelumab in combination with IL-15 superagonist N-803 and nab-paclitaxel (Abraxane) is presented. Avelumab treatment alone resulted in a response in a para-aortic lesion, but not the other tumor masses. N-803 was added, followed by nab-paclitaxel; CT showed a decrease in the size of the abdominal mass at 1 month, near resolution at 3 months and CR at 5 months. Abraxane was discontinued after the first CR on CT, and the patient continues on avelumab/N-803 treatment and maintains a CR. Combination of avelumab with low/moderate-dose chemotherapy and an immune enhancer such as N-803 may offer a viable treatment option for MCC patients for whom avelumab therapy alone was not effective.

Micronutrients are known to modulate host immunity, and there is limited literature on this association in the context of dengue virus infection (DENV).
Using a nested case-control design in a surveillance program, we measured the following: anthropometry; nutritional biomarkers including serum ferritin, soluble transferrin receptor, retinol-binding protein (RBP), 25-hydroxy vitamin D, folate, and vitamin B12; and a panel of immune response markers. We then compared these measures across 4 illness categories: healthy control, nonfebrile DENV, other febrile illness (OFI), and apparent DENV using multivariate polytomous logistic regression models.
Among 142 participants, serum ferritin (ng/mL) was associated with apparent DENV compared to healthy controls (odds ratio [OR], 2.66; confidence interval [CI], 1.53-4.62; P = .001), and RBP concentrations (µmol/L) were associated with apparent DENV (OR, 0.03; CI, 0.00-0.30; P = .003) and OFI (OR, 0.02; CI, 0.00-0.24; P = .003). In a subset of 71 participants, interleukin-15 levels (median fluorescent intensity) were positively associated with apparent DENV (OR, 1.09; CI, 1.03-1.14; P = .001) and negatively associated with nonfebrile DENV (OR, 0.89; CI, 0.80-0.99; P = .03) compared to healthy controls.
After adjusting for the acute-phase response, serum ferritin and RBP concentrations were associated with apparent DENV and may represent biomarkers of clinical importance in the context of dengue illness.

The clinical validity and utility of complex biomarkers have not been extensively studied in bladder cancer. Three patients with nonmuscle invasive bladder cancer [1 patient with an exceptional response; complete response (CR) for 30 months] who failed intravesical BCG were evaluated using an NYS CLEP approved assay, Immune Report Card, which measures programmed death-ligand 1 expression, CD8 T-cell infiltration pattern, mutational burden, and gene expression of 51 immune-related transcripts using RNA-Seq. Patients were tested before being treated under our expanded access protocol for intravesical BCG with ALT-803. Subject 1 had failed his fourth line of therapy, subject 2 had failed only his first line of therapy, and subject 3 had failed his seventh line of therapy. Surprisingly, subject 1 had an unusually prolonged CR which lasted 30 months; subject 2 had the persistent and recurrent disease until 12 months when he then developed a CR; subject 3 had disease recurrence at 3 months, along with progression noted at 6 months. Immunomutational status was extensively evaluated to identify potential alterations that might play a role as predictive markers for subject 1, who had an exceptional response. Compared with subject 3, tumor in subject 1 demonstrated a high level of expression for CTLA4 (immunosuppression) and CD39 (immunosuppressive). Together, an immunosuppressive tumor environment in nonmuscle invasive bladder cancer that have failed prior BCG may respond better to interleukin-15 immunotherapy compared with tumors without an immunosuppressive environment.

BACKGROUND: Basiliximab and etanercept have achieved promising responses in steroid-refractory graft versus host disease (SR-GVHD). However, the in vivo immune changes following the treatment have not been elucidated.
METHODS: A 14-year-old boy presented with skin rash and diarrhea 20 days after haploidentical hemotopoietic stem cell transplantation.
METHODS: We made the diagnose of grade 3 acute GVHD with skin and gastrointestinal involvement.
METHODS: After the failure of the first-line treatment with methylprednisolone, combined anti-cytokine therapies with basiliximab and etanercept were prescibed.
RESULTS: He achieved complete remission by basiliximab and etanercept. Furthermore, we detected that donor CD3CD56 Natural killer T(NKT)-like cells expanded gradually after the period of lymphocytopenia caused by GVHD and anti-cytokine therapy. The expansion of NKT-like cells was in association with high serum IFN-γ. NKT-like cells showed preferred proliferation in response to IFN-γ and potent cytotoxicity against leukemia cells. The expansion persisted > 2 years and the patient had a leukemia-free survival of 66 months.
CONCLUSIONS: Our case indicated that combined anti-cytokine treatment may reset the immune system and cause NKT-like cells to exhibit a predilection for expansion.

The molecular regulation of muscle function in knee osteoarthritis is unclear. Elevated muscle atrophy regulation marker expression was associated with reduced muscle strength in knee osteoarthritis. The level of protein expression appears to be different between muscle, knee joint and serum, suggesting that inflammation is regulated differently within these tissues.
Impaired muscle function is common in knee osteoarthritis (OA). Numerous biochemical molecules have been implicated in the development of OA; however, these have only been identified in the joint and serum. We compared the expression of interleukin-15 (IL-15) and Forkhead box protein-O1 (FoxO1) in muscle of patients with knee OA and asymptomatic individuals and examined whether IL-15 was also present in the joint and serum.
Muscle and blood samples were collected from 19 patients with knee OA and 10 age-matched asymptomatic individuals. Synovial fluid and muscle biopsies were collected from the OA group during knee replacement surgery. IL-15 and FoxO1 were measured in the skeletal muscle. IL-15 abundance was also analysed in the serum of both groups and synovial fluid from the OA group. Knee extensor strength was measured and correlated with IL-15 and FoxO1 in the muscle.
FoxO1 protein expression was higher (p = 0.04), whereas IL-15 expression was lower (p = 0.02) in the muscle of the OA group. Strength was also lower in the OA group and was inversely correlated with FoxO1 expression. No correlation was found between IL-15 in the joint, muscle or serum.
Skeletal muscle, particularly the quadriceps, is affected in people with knee OA where elevated FoxO1 protein expression was associated with reduced muscle strength. While IL-15 protein expression in the muscle was lower in the knee OA group, no correlation was found between the expression of IL-15 protein in the muscle, joint and serum, which suggests that inflammation is regulated differently within these tissues. Australian Clinical Trials Registry (ACTR) number: ACTRN12613000467730 ( http://www.anzctr.org.au/TrialSearch.aspx?searchTxt=ACTRN12613000467730&isBasic=True ).

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Janus kinase 3-severe combined immunodeficiency (JAK3-SCID) is an autosomal recessive immunodeficiency disease caused by various mutations in the JAK3 gene. Typical JAK3-SCID is characterized by a phenotype in which B cells are present but T and NK cells are not, the T(-)B(+)NK(-) phenotype, and by impaired signaling through cytokine receptors that use the common gamma chain (gammac) subunit. An atypical JAK3-SCID case carrying a single glutamate to glycine substitution mutation (E481G) in the JH3 domain of one JAK3 allele, and a deletion mutation (del482-596) in the JH3 and JH2 domains of the other allele was reported previously. Although this patient had CD4(+) T cells and NK cells unlike typical cases, the CD4(+) T cells were functionally impaired. We report here that the JAK3-E481G mutant transduced IL-2-, IL-4-, IL-15-, and IL-21-induced signals as efficiently as wild-type JAK3. However, this mutant failed to respond to IL-7 by phosphorylating JAK1, JAK3, or STAT5. The other mutant JAK3, JAK3-del482-596, was non-functional. Thus, an impaired IL-7 signal may cause SCID and compromise T-cell differentiation, even if the IL-15 signal is preserved and supports NK-cell development, as in this patient.