Substance use disorder status moderates the association between personality traits and problematic mobile phone/internet use

Background: Associations between personality traits and problematic smartphone use (PSU) among individuals with substance use disorder (SUD) have not been widely investigated. The current study aims to assess whether SUD status moderates the association between personality traits and PSU. Methods: The study group included 151 individuals with SUD and a normative sample (NS) comprised of 554 non-SUD students. The following self-report questionnaires were used: the Mobile Phone Problem Use Scale (MPPUS-10) to assess problematic smartphone use (PSU), the Internet Addiction Test (IAT) to assess intensity of internet use, and the NEO Five-Factor Inventory (NEO-FFI) to assess Personality traits. Results: SUD status moderated the association between neuroticism and openness to new experiences on PSU. That is, greater neuroticism and openness were significantly associated with more excessive PSU among the NS. In the SUD group, greater openness was a significant protective factor against PSU. Moderation results were similar when using the IAT (which was significantly correlated with MPPUS) as an outcome. Conclusions: The presence of SUD may influence how personality traits are associated with problematic mobile phone/internet use. Given that this is among one of the first studies examining this topic, findings should be replicated with additional studies

Evaluation of the role of downregulation of SNF5/INI1 core subunit of SWI/SNF complex in clear cell renal cell carcinoma development

Clear cell renal cell carcinoma (ccRCC) is characterized by stabilization of hypoxia-inducible factor (HIF1), and mutations in von Hippel-Lindau (VHL) gene. Additionally, in about 40% of ccRCC cases the mutation in PBRM1 (POLYBROMO1) gene coding for a non-core subunit of SWI/SNF chromatin remodeling complex was found suggesting potential impairment of this complex function in ccRCC. In this study we assessed the extent to which the core SWI/SNF complex subunit - INI1 (hSNF5/SMARCB1) is affected in ccRCC and whether it has any consequences on the development of this type of cancer. The evaluation of INI1 protein level in samples from 50 patients with diagnosed ccRCC, including three displaying rhabdoid features, showed the INI1 positive staining in rhabdoid cells while the conventional ccRCC cells exhibited reduced INI1 level. This indicated the rhabdoid component of ccRCC as distinct from other known rhabdoid tumors. The reduced INI1 protein level observed in all conventional ccRCC cases used in this study correlated with decreased SMARCB1 gene expression at the transcript level. Consistently, the overexpression of INI1 protein in A498 ccRCC cell line resulted in the elevation of endogenous SMARCB1 transcript level indicating that the INI1-dependent regulatory feedback loop controlling expression of this gene is affected in ccRCC Moreover, the set of INI1 target genes including i.e. CXCL12/CXCR7/CXCR4 chemokine axis was identified to be affected in ccRCC. In summary, we demonstrated that the inactivation of INI1 may be of high importance for ccRCC development and aggressiveness

hCG-secreting malignancies – diagnostic pitfalls

We present a case of a 34-year-old male patient referred to our Uro-oncology Department with a suspicion of a metastatic germ cell tumour, owing to enlarged left testicle and elevated b-hCG concentration (39 mIU/mL). Impaired performance status caused by extensive pulmonary and liver metastases, accompanied by significant lymphadenopathy, necessitated prompt management. However, a testicular tumour was excluded on ultrasound imaging; a hydrocele only was found. The b-hCG concentration was not increasing (37 mIU/mL). We found a diagnosis of an extragonadal germ cell tumour doubtful, and a liver biopsy was performed. Due to the patient’s quick deterioration, we decided to commence pre-phase chemotherapy with cisplatin and etoposide, which resulted in a significant clinical improvement. The pathological examination, along with immunoassays, revealed undifferentiated cholangiocarcinoma, and the patient continued chemotherapy with a biliary tract cancer regimen, i.e. cisplatin and gemcitabine. Unfortunately, the clinical response was short-lived; the disease progressed, the patient was offered best supportive care and died two months after the diagnosis. The case underpins the literature review with respect to differential diagnosis of an elevated hCG concentration. In particular, we discuss ectopic secretion in non-trophoblastic and non-germinal malignancies and the causes of false positive assays.We present a case of a 34-year-old male patient referred to our Uro-oncology Department with a suspicion of a metastatic germ cell tumour, owing to enlarged left testicle and elevated β-hCG concentration (39 mIU/ml). Impaired performance status caused by extensive pulmonary and liver metastases, accompanied by significant lymphadenopathy, necessitated prompt management. However, a testicular tumour was excluded by ultrasound examination; a hydrocele only was found. The β-hCG concentration was not increasing (37 mIU/ml). We found a diagnosis  of an extragonadal germ cell tumour doubtful, and a liver biopsy was performed.  Due to the patient’s quick deterioration, we decided to commence pre-phase chemotherapy with cisplatin and etoposide, which resulted in a significant clinical improvement. The pathological examination, along with immunoassays, revealed undifferentiated cholangiocarcinoma, and the patient continued chemotherapy  with a biliary tract cancer regimen, i.e. cisplatin and gemcitabine. Unfortunately, the clinical response was short-lived; the disease progressed, the patient was offered best supportive care and died two months after the diagnosis. The case underpins the literature review with respect to differential diagnosis  of an elevated hCG concentration. In particular, we discuss ectopic secretion  in non-trophoblastic and non-germinal malignancies and the causes of false positive assays

Human isotype‐dependent inhibitory antibody responses against Mycobacterium tuberculosis

Accumulating evidence from experimental animal models suggests that antibodies play a protective role against tuberculosis (TB). However, little is known about the antibodies generated upon Mycobacterium tuberculosis (MTB) exposure in humans. Here, we performed a molecular and functional characterization of the human B‐cell response to MTB by generating recombinant monoclonal antibodies from single isolated B cells of untreated adult patients with acute pulmonary TB and from MTB‐exposed healthcare workers. The data suggest that the acute plasmablast response to MTB originates from reactivated memory B cells and indicates a mucosal origin. Through functional analyses, we identified MTB inhibitory antibodies against mycobacterial antigens including virulence factors that play important roles in host cell infection. The inhibitory activity of anti‐MTB antibodies was directly linked to their isotype. Monoclonal as well as purified serum IgA antibodies showed MTB blocking activity independently of Fc alpha receptor expression, whereas IgG antibodies promoted the host cell infection. Together, the data provide molecular insights into the human antibody response to MTB and may thereby facilitate the design of protective vaccination strategies

Sorafenib dose escalation in treatment-naïve patients with metastatic renal cell carcinoma: a non-randomised, open-label, Phase 2b study.

Objective To assess the efficacy and safety of sorafenib dose escalation in metastatic renal cell carcinoma (mRCC).Patients and methods Intra-patient dose escalation may enhance the clinical benefit of targeted anticancer agents in metastatic disease. In this non-randomised, open-label, Phase 2b study, treatment-naïve patients with mRCC were initially treated with the standard oral sorafenib dose [400 mg twice daily (BID)]. Two dose escalations were planned, each 200 mg BID after 28 days at the prior level. Dose reductions, interruptions, or delayed escalations were used to manage adverse events (AEs). The primary endpoint was objective response rate (ORR) in the modified intent-to-treat (mITT) population, which comprised patients with ≥6 months of treatment including ≥4 months of therapy at their highest tolerated dose. Secondary endpoints included progression-free survival (PFS) and safety.Results In all, 83 patients received sorafenib. The dose received for the longest duration was 400, 600, and 800 mg BID in 48.2%, 15.7%, and 24.1% of patients, respectively. The ORR was 44.4% [n = 8/18; 95% confidence interval (CI) 21.5-69.2] and 17.9% (n = 12/67; 95% CI 9.6-29.2) in the mITT and ITT populations, respectively. The median (95% CI) PFS was 7.4 (6.0-11.7) months (ITT). The most common AEs of any grade were hand-foot skin reaction (66.3%) and diarrhoea (63.9%).Conclusion Sorafenib demonstrated clinical benefit in treatment-naïve patients with mRCC. However, relatively few patients could sustain doses of >400 mg BID. There was evidence that, where tolerated, escalation from the standard sorafenib dose may have enhanced clinical benefit. However, this study does not support dose escalation for most patients with treatment-naïve mRCC. Alternative protocols for sorafenib dose escalation could be explored

Succinate Dehydrogenase-Deficient Renal Cancer Featuring Fructose-1,6-Biphosphatase Loss, Pyruvate Kinase M2 Overexpression, and SWI/SNF Chromatin Remodeling Complex Aberrations: A Rare Case Report

Succinate dehydrogenase (SDH)-deficient renal cancer is a rare renal cancer subtype recently accepted by the World Health Organization as a unique subtype of renal cell carcinoma (RCC). Here we report a case of 17-year old man. The detailed evaluation indicated occurrence of the SDHB-deficient RCC. The genetic testing revealed no germline mutation in SDH genes. Immunohistochemistry showed SDHB deficiency, overexpression of pyruvate kinase M2 and dramatic downregulation of fructose-1,6-bisphosphatase metabolic enzymes, and unaltered levels of phosphorylated AMP-activated protein kinase and mammalian target of rapamycin. Strong upregulation of INI1 and BRG1 and overexpression of BAF180, subunits of SWI/SNF ATP-dependent chromatin remodeling complex, were also found. The identified tumor pathologically did not resemble clear cell renal cell carcinoma (ccRCC), but some metabolic alterations are common for both cancer types. Thus, we postulate that the phenotypical differences between ccRCC and SDHB-deficient RCC may be related to distinct molecular and metabolic alterations