In light of the burgeoning successes of cancer immunotherapy, glioblastoma (GBM) remains refractory due to an immunosuppressive microenvironment originating from its molecular heterogeneity. Thus, identifying promising therapeutic targets for treating GBM and discovering methodologies to effectively regulate them is still a tremendous challenge. Here we describe photodynamic protein tyrosine phosphatase 1B (PTP1B) proteolysis mediated by a proteolysis-targeting chimera (PROTAC) nanoassembly. The PTP1B-targeting PROTAC is conjugated with a photosensitizer via a cathepsin B (Cat B)-cleavable peptide, which spontaneously forms nanoassemblies due to intermolecular π-π stacking interactions. In GBM models, PROTAC nanoassemblies significantly accumulate in the tumor region across the disrupted blood-brain barrier (BBB), triggering a burst release of the photosensitizer and active PROTAC by Cat B-mediated enzymatic cleavage. Upon laser irradiation, photodynamic therapy (PDT) synergizes with PROTAC-mediated PTP1B proteolysis to induce potent immunogenic cell death (ICD) in tumor cells. Subsequently, persistent PTP1B degradation by nanoassemblies in Cat B-overexpressed intratumoral T cells downregulates exhaustion markers, reinvigorating their functionality. These sequential processes of photodynamic PTP1B proteolysis ultimately augment T cell-mediated antitumor immunity as well as protective immunity, completely eradicating the primary GBM and preventing its recurrence. Overall, our findings underscore the therapeutic potential of combining PDT with PROTAC activity for GBM immunotherapy.

A 7-year-old castrated male Persian cat presented with a cutaneous mass and an increase in serum amyloid A concentration. Fine needle aspirates of the mass indicated lymphoma, which was also the top differential diagnosis on histopathologic examinations. Immunohistochemically, neoplastic cells tested negative for anti-CD3, PAX5, CD20, and c-Kit, but positive for MUM1, CD79α, and CD138, suggesting extramedullary plasmacytoma. There were tumor-infiltrating non-neoplastic CD3+ T and CD20+ B cells. Practitioners should be aware of feline plasmacytoma characterized by lymphoma-like cytologic and histologic features. The present study is valuable in providing the first clinical evidence that proves the immunogenicity of feline plasmacytoma.

A 7-year-old castrated male Persian cat presented with a cutaneous mass and an increase in serum amyloid A concentration. Fine needle aspirates of the mass indicated lymphoma, which was also the top differential diagnosis on histopathologic examinations. Immunohistochemically, neoplastic cells tested negative for anti-CD3, PAX5, CD20, and c-Kit, but positive for MUM1, CD79α, and CD138, suggesting extramedullary plasmacytoma. There were tumor-infiltrating non-neoplastic CD3+ T and CD20+ B cells. Practitioners should be aware of feline plasmacytoma characterized by lymphoma-like cytologic and histologic features. The present study is valuable in providing the first clinical evidence that proves the immunogenicity of feline plasmacytoma.

A 7-year-old castrated male Persian cat presented with a cutaneous mass and an increase in serum amyloid A concentration. Fine needle aspirates of the mass indicated lymphoma, which was also the top differential diagnosis on histopathologic examinations. Immunohistochemically, neoplastic cells tested negative for anti-CD3, PAX5, CD20, and c-Kit, but positive for MUM1, CD79α, and CD138, suggesting extramedullary plasmacytoma. There were tumor-infiltrating non-neoplastic CD3+ T and CD20+ B cells. Practitioners should be aware of feline plasmacytoma characterized by lymphoma-like cytologic and histologic features. The present study is valuable in providing the first clinical evidence that proves the immunogenicity of feline plasmacytoma.

A 7-year-old castrated male Persian cat presented with a cutaneous mass and an increase in serum amyloid A concentration. Fine needle aspirates of the mass indicated lymphoma, which was also the top differential diagnosis on histopathologic examinations. Immunohistochemically, neoplastic cells tested negative for anti-CD3, PAX5, CD20, and c-Kit, but positive for MUM1, CD79α, and CD138, suggesting extramedullary plasmacytoma. There were tumor-infiltrating non-neoplastic CD3+ T and CD20+ B cells. Practitioners should be aware of feline plasmacytoma characterized by lymphoma-like cytologic and histologic features. The present study is valuable in providing the first clinical evidence that proves the immunogenicity of feline plasmacytoma.

A 7-year-old castrated male Persian cat presented with a cutaneous mass and an increase in serum amyloid A concentration. Fine needle aspirates of the mass indicated lymphoma, which was also the top differential diagnosis on histopathologic examinations. Immunohistochemically, neoplastic cells tested negative for anti-CD3, PAX5, CD20, and c-Kit, but positive for MUM1, CD79α, and CD138, suggesting extramedullary plasmacytoma. There were tumor-infiltrating non-neoplastic CD3+ T and CD20+ B cells. Practitioners should be aware of feline plasmacytoma characterized by lymphoma-like cytologic and histologic features. The present study is valuable in providing the first clinical evidence that proves the immunogenicity of feline plasmacytoma.

Background: This study evaluated the prevalence of Helicobacter pylori infection and the risk factors associated with H. pylori transmission among spouses. Methods: We assessed the spousal concurrence of H. pylori infection using the Campylobacter-like organism (CLO) test under gastro-endoscopy in 132 couples. Based on the CLO test results, participants were categorized into H. pylori concurrent and independent groups. The chi-square test and Student t-test were performed for demographic comparisons between the concurrent and independent H. pylori groups. In addition, multivariate logistic regression analysis was performed to identify factors associated with concurrent H. pylori infection. Results: The study revealed that the concurrence rate of H. pylori infection was 42.4% in married Korean couples. The odds ratio (OR) derived from the concurrence of H. pylori infection tended to decrease in older couples (OR, 0.975; 95% confidence interval [CI], 0.949–1.002; P=0.072). Gastric erosion was also associated with a decreased OR for concurrent infection (OR, 0.488; 95% CI, 0.295–0.808; P=0.005). Conversely, active duodenal ulcers were associated with an increased OR for concurrent infections (OR, 6.501; 95% CI, 1.267–33.346; P=0.025). Duodenal ulcer scars tended to increase the OR of concurrent infections (OR, 1.392; 95% CI, 0.815–2.380; P=0.226). Conclusion Spousal transmission and concurrence of H. pylori infection were negatively associated with gastric erosion; however, they were positively associated with active duodenal ulcers. Further studies are warranted to elucidate the mechanisms underlying these findings.

PURPOSE: Anaphylaxis is an immediate allergic reaction characterized by potentially life-threatening, severe, systemic manifestations. While studies have evaluated links between serious illness and posttraumatic stress disorder (PTSD), few have investigated PTSD after anaphylaxis in adults. We sought to investigate the psychosocial burden of recent anaphylaxis in Korean adults.METHODS: A total of 203 (mean age of 44 years, 120 females) patients with anaphylaxis were recruited from 15 university hospitals in Korea. Questionnaires, including the Impact of Event Scale-Revised-Korean version (IES-R-K), the Korean version of the Beck Anxiety Inventory (K-BAI), and the Korean version of the Beck Depression Inventory (K-BDI), were administered. Demographic characteristics, causes and clinical features of anaphylaxis, and serum inflammatory markers, including tryptase, platelet-activating factor, interleukin-6, tumor necrosis factor-α, and C-reactive protein, were evaluated.RESULTS: PTSD (IES-R-K ≥ 25) was noted in 84 (41.4%) patients with anaphylaxis. Of them, 56.0% had severe PTSD (IES-R-K ≥ 40). Additionally, 23.2% and 28.1% of the patients had anxiety (K-BAI ≥ 22) and depression (K-BDI ≥ 17), respectively. IES-R-K was significantly correlated with both K-BAI (r = 0.609, P < 0.0001) and K-BDI (r = 0.550, P < 0.0001). Among the inflammatory mediators, tryptase levels were lower in patients exhibiting PTSD; meanwhile, platelet-activating factor levels were lower in patients exhibiting anxiety and depression while recovering from anaphylaxis. In multivariate analysis, K-BAI and K-BDI were identified as major predictive variables of PTSD in patients with anaphylaxis.CONCLUSIONS: In patients with anaphylaxis, we found a remarkably high prevalence of PTSD and associated psychological distresses, including anxiety and depression. Physicians ought to be aware of the potential for psychological distress in anaphylactic patients and to consider psychological evaluation.
Adult ; Anaphylaxis ; Anxiety ; C-Reactive Protein ; Depression ; Hospitals, University ; Humans ; Hypersensitivity ; Interleukin-6 ; Korea ; Multivariate Analysis ; Necrosis ; Prevalence ; Prospective Studies ; Stress Disorders, Post-Traumatic ; Tryptases

Objective: : Unclear mental state is one of the major factors contributing to diagnostic failure of occult skeletal trauma in patients with traumatic brain injury (TBI). The aim of this study was to evaluate the overlooked co-occurring skeletal trauma through whole body bone scan (WBBS) in TBI. Methods: : A retrospective study of 547 TBI patients admitted between 2015 and 2017 was performed to investigate their cooccurring skeletal injuries detected by WBBS. The patients were divided into three groups based on the timing of suspecting skeletal trauma confirmed : 1) before WBBS (pre-WBBS); 2) after the routine WBBS (post-WBBS) with good mental state and no initial musculoskeletal complaints; and 3) after the routine WBBS with poor mental state (poor MS). The skeletal trauma detected by WBBS was classified into six skeletal categories : spine, upper and lower extremities, pelvis, chest wall, and clavicles. The skeletal injuries identified by WBBS were confirmed to be simple contusion or fractures by other imaging modalities such as X-ray or computed tomography (CT) scans. Of the six categorizations of skeletal trauma detected as hot uptake lesions in WBBS, the lesions of spine, upper and lower extremities were further statistically analyzed to calculate the incidence rates of actual fractures (AF) and actual surgery (AS) cases over the total number of hot uptake lesions in WBBS. Results: : Of 547 patients with TBI, 112 patients (20.4 %) were presented with TBI alone. Four hundred and thirty-five patients with TBI had co-occurring skeletal injuries confirmed by WBBS. The incidences were as follows : chest wall (27.4%), spine (22.9%), lower extremities (20.2%), upper extremities (13.5%), pelvis (9.4%), and clavicles (6.3%). It is notable that relatively larger number of positive hot uptakes were observed in the groups of post-WBBS and poor MS. The percentage of post-WBBS group over the total hot uptake lesions in upper and lower extremities, and spines were 51.0%, 43.8%, and 41.7%, respectively, while their percentages of AS were 2.73%, 1.1%, and 0%, respectively. The percentages of poor MS group in the upper and lower extremities, and spines were 10.4%, 17.4%, and 7.8%, respectively, while their percentages of AS were 26.7%, 14.2%, and 11.1%, respectively. There was a statistical difference in the percentage of AS between the groups of post-WBBS and poor MS (p=0.000). Conclusion : WBBS is a potential diagnostic tool in understanding the skeletal conditions of patients with head injuries which may be undetected during the initial assessment.