The biopsychosocial-spiritual factors influencing relapse of patients with schizophrenia

Objective: High relapse rate of patients with schizophrenia has a large impact on patients and their families that can be reviewed from biopsychosocial and spiritual factors. Determining all the potential risk factors of relapse in schizophrenia can help increase awareness of physicians, patients, and families. Physicians are the ones who examine patients and have responsibility to manage and educate them and expect to prevent relaps. This study analyze various biopsychosocial and spiritual factors affecting relapse occurrence in patients with schizophrenia. Methods: Cross sectional observational analytic study on 226 subjects with schizophrenia in three places in East Java, Indonesia, namely Soetomo Academic Hospital Surabaya (33.2%), Menur Hospital Surabaya (32.7%), and Radjiman Wediodiningrat Mental Hospital Lawang (34.1%) that met the inclusion and exclusion criteria. Data collection including 33 biopsychosocial and spiritual factors and were analyzed using bivariate and multivariate logistic regression. Results: Relapse rate within 1 year was 59.73%. There were 12 factors significantly affected the relapse of schizophrenia, namely history of physical disease of mothers during pregnancy ( p < .001; B = 27.31; 95% CI 3.96–188.52), presence of trigger ( p < .000; B = 6.25; 95% CI 2.61–14.96), negative beliefs ( p < .000; B = 4.94; 95% CI 2.10–11.61), hereditary factors ( p < .001; B = 4.84; 95% CI 1.93–12.10), insight ( p < .003; B = 4.27; 95% CI 1.62–11.27), 1-year GAF Scale ( p < .015; B = 3.79; 95% CI 1.30–11.09), response to treatment ( p < .006; B = 3.68; 95% CI 1.45–9.36), family knowledge ( p < .011; B = 3.23; 95% CI 1.31–7.93), history of head trauma ( p < .029; B = 3.13; 95% CI 1.13–8.69), medication side effects ( p < .028; B = 2.92; 95% CI 1.12–7.61), substance use history ( p < .031; B = 2.86; 95% CI 1.10–7.45), and occupation ( p < .040; B = 2.40; 95% CI 1.04–5.52). Conclusions: The 12 factors of biopsychosocial-spiritual are determinant to predict the risk of relapse in patients with schizophrenia. These factors should be emphasized in psychoeducation for patients and their families to enable intervention and relapse prevention.

Organ-Preserving Surgery in Urethral Cancer (a Clinical Case)

Background. Despite low incidence, malignant urethral neoplasms are among the most aggressive tumours. Prevalence of muscle-invasive and metastatic cancer at diagnosis, as well as a high relapse rate compel adherence to the most radical treatment. At the same time, the high incidence of urethral tumours in elderly and senile patients and high postoperative complication rates warrant the development of organ-preserving treatment.Aim. A case description to verify the organ-preserving treatment applicability in urethral cancer.Materials and methods. We report the treatment experience in a senile patient with concomitant chronic kidney disease at the Volgograd Regional Clinical Oncology Dispensary’s Oncourology Unit. Accounting for the age, concomitant pathology and tumour histology factors, a minimally invasive organ-preserving surgical intervention was performed as laparoscopic urethral resection with ureterocystoneostomy.Results and discussion. Renal function was assessed in postoperative period with dynamic nephroscintigraphy and blood creatinine monitoring. Control cysto-, ureteroscopy and contrast-enhanced CT scanning in areas of interest were performed to rule out relapse and progression.Conclusion. No report of disease relapse or progression at follow-up indicates the oncological safety of organ-preserving surgery in this patient category. Th is approach also gains support from immediate and long-term outcomes of the patient’s improved renal function and sustained good quality of life.

Clonal Evolution Pattern and Prognostic Significance of Clonal Architecture in KMT2A-Rearranged Acute Myeloid Leukemia

MLL (KMT2A) rearrangements are among the most frequent chromosomal abnormalities that occur in acute myeloid leukemia (AML). Mutational landscapes in KMT2A-rearranged AML have been reported; however, most studies are missing data at relapse. Therefore, matched diagnostic and relapse samples were analyzed in this study, and the clonal evolution pattern in KMT2A-rearranged AML was examined. Further, the prognostic significance of the clonal architecture was investigated. Sixty-two diagnostic and 16 relapse samples obtained from pediatric patients with KMT2A-rearranged AML enrolled in the Japan Children's Cancer Group (JCCG) AML-05/AML-99 study were analyzed for 338 genes using targeted sequencing. The data were analyzed with the published data of 105 diagnostic and 9 relapse samples with KMT2A-rearranged AML. Additionally, as a control, the mutation data of matched diagnostic and relapse samples of 107 patients with non-KMT2A-rearranged AML were collected. Among 25 patients with KMT2A-rearranged AML with matched data at diagnosis and relapse, mutations of signaling pathway genes (FLT3, KRAS, NRAS, PTPN11, CBL, and BRAF) were frequently detected in diagnostic samples (25 mutations/25 patients). However, 21 of 25 (84.0%) mutations were lost at relapse. In contrast, 7 of 19 (36.8%) mutations of other pathway genes were lost at relapse, and the percentage was significantly lower than that of mutations in the signaling pathway genes (P = 0.002). Six mutations in the signaling pathway genes and 11 mutations in other pathway genes were acquired at relapse. Particularly, mutations of transcription factor genes (WT1, SPI1, GATA2, and RUNX1) were acquired at relapse: 7 of 8 (87.5%) mutations were detected only at relapse. These results suggest that mutations of signaling pathway genes are unstable in the clonal evolution of KMT2A-rearranged AML. Mutations of other pathway genes, especially those of transcription factor genes, may contribute to relapse in patients with KMT2A-rearranged AML. Next, attention was turned to the KRAS mutations (KRAS-MT) because we have previously shown that KRAS-MT are independent adverse prognostic factors in KMT2A-rearranged AML (Blood Adv. 2020). Among 25 patients with KMT2A-rearranged AML with matched data at diagnosis and relapse, 10 (40.0%) patients harbored KRAS-MT at diagnosis. Interestingly, KRAS-MT were lost at relapse in 9 of 10 (90.0%) patients. Among 107 patients with non-KMT2A-rearranged AML with matched data at diagnosis and relapse, 10 (9.3%) patients harbored KRAS-MT at diagnosis. The frequency of KRAS-MT was significantly higher in KMT2A-rearranged AML (40.0% vs. 9.3%, P = 0.0006). This may be explained on the basis of the fact that KRAS-MT is associated with a high relapse rate in KMT2A-rearranged AML, but not in non-KMT2A-rearranged AML. KRAS-MT was lost at relapse in 5 of 10 (50.0%) patients with non-KMT2A-rearranged AML. The percentage of KRAS-MT loss at relapse was higher in KMT2A-rearranged AML. However, it was not statistically significant (90.0% vs. 50.0%, P = 0.14). Therefore, KRAS-MT may be unstable in clonal evolution regardless of disease subtypes in AML. The underlying mechanisms of the paradox between the high relapse rate in patients with KRAS-MT and frequent loss of KRAS-MT at relapse in patients with KMT2A-rearranged AML should be examined in future studies. The loss of KRAS-MT at relapse suggests that the mutations were in subclones at diagnosis. Therefore, we finally examined the prognosis of 167 patients according to the clonality of KRAS-MT at diagnosis. In patients with KMT2A-MLLT3 (n = 67), those with subclonal KRAS-MT (n = 6) had adverse 5-y event-free survival compared with both patients with wild-type KRAS (KRAS-WT) (n = 56) (KRAS-WT vs. subclonal KRAS-MT: 58.7% vs. 16.7%, P = 0.04) and patients with clonal KRAS-MT (n = 5) (clonal KRAS-MT vs. subclonal KRAS-MT: 80.0% vs. 16.7%, P = 0.07). However, 5-y overall survival (OS) was similar among the three groups. In contrast, among patients with KMT2A-MLLT10 (n = 37), those with clonal KRAS-MT (n = 5) had adverse 5-y OS compared with both patients with KRAS-WT (n = 20) (KRAS-WT vs. clonal KRAS-MT: 59.7% vs. 0.0%, P = 0.006) and patients with subclonal KRAS-MT (n = 12) (subclonal KRAS-MT vs. clonal KRAS-MT: 58.3% vs. 0.0%, P = 0.04). According to these results, the effects of the clonality of KRAS-MT on prognosis may depend on which KMT2A fusion is present. Disclosures Nannya: Otsuka Pharmaceutical Co., Ltd.: Consultancy, Speakers Bureau; Astellas: Speakers Bureau. Saito: Toshiba corporation: Research Funding. Ogawa: Kan Research Laboratory, Inc.: Consultancy, Research Funding; Otsuka Pharmaceutical Co., Ltd.: Research Funding; Dainippon-Sumitomo Pharmaceutical, Inc.: Research Funding; Eisai Co., Ltd.: Research Funding; Ashahi Genomics: Current holder of individual stocks in a privately-held company; ChordiaTherapeutics, Inc.: Consultancy, Research Funding.

Insights from Leishmania (Viannia) guyanensis in vitro behavior and intercellular communication

Background Pentavalent antimonial-based chemotherapy is the first-line approach for leishmaniasis treatment and disease control. Nevertheless antimony-resistant parasites have been reported in some endemic regions. Treatment refractoriness is complex and is associated with patient- and parasite-related variables. Although amastigotes are the parasite stage in the vertebrate host and, thus, exposed to the drug, the stress caused by trivalent antimony in promastigotes has been shown to promote significant modification in expression of several genes involved in various biological processes, which will ultimately affect parasite behavior. Leishmania (Viannia) guyanensis is one of the main etiological agents in the Amazon Basin region, with a high relapse rate (approximately 25%). Methods Herein, we conducted several in vitro analyses with L. (V.) guyanensis strains derived from cured and refractory patients after treatment with standardized antimonial therapeutic schemes, in addition to a drug-resistant in vitro-selected strain. Drug sensitivity assessed through Sb(III) half-maximal inhibitory concentration (IC50) assays, growth patterns (with and without drug pressure) and metacyclic-like percentages were determined for all strains and compared to treatment outcomes. Finally, co-cultivation without intercellular contact was followed by parasitic density and Sb(III) IC50 measurements. Results Poor treatment response was correlated with increased Sb(III) IC50 values. The decrease in drug sensitivity was associated with a reduced cell replication rate, increased in vitro growth ability, and higher metacyclic-like proportion. Additionally, in vitro co-cultivation assays demonstrated that intercellular communication enabled lower drug sensitivity and enhanced in vitro growth ability, regardless of direct cell contact. Conclusions Data concerning drug sensitivity in the Viannia subgenus are emerging, and L. (V.) guyanensis plays a pivotal epidemiological role in Latin America. Therefore, investigating the parasitic features potentially related to relapses is urgent. Altogether, the data presented here indicate that all tested strains of L. (V.) guyanensis displayed an association between treatment outcome and in vitro parameters, especially the drug sensitivity. Remarkably, sharing enhanced growth ability and decreased drug sensitivity, without intercellular communication, were demonstrated. Graphical Abstract

Prognostic impact of chromosomal abnormalities and copy number alterations in adult B-cell precursor acute lymphoblastic leukaemia: a UKALL14 study

Chromosomal abnormalities are established prognostic markers in adult ALL. We assessed the prognostic impact of established chromosomal abnormalities and key copy number alterations (CNA) among 652 patients with B-cell precursor ALL treated on a modern MRD driven protocol. Patients with KMT2A-AFF1, complex karyotype (CK) and low hypodiploidy/near-triploidy (HoTr) had high relapse rates 50%, 60% & 53% and correspondingly poor survival. Patients with BCR-ABL1 had an outcome similar to other patients. JAK-STAT abnormalities (CRLF2, JAK2) occurred in 6% patients and were associated with a high relapse rate (56%). Patients with ABL-class fusions were rare (1%). A small group of patients with ZNF384 fusions (n = 12) had very good survival. CNA affecting IKZF1, CDKN2A/B, PAX5, BTG1, ETV6, EBF1, RB1 and PAR1 were assessed in 436 patients. None of the individual deletions or profiles were associated with survival, either in the cohort overall or within key subgroups. Collectively these data indicate that primary genetic abnormalities are stronger prognostic markers than secondary deletions. We propose a revised UKALL genetic risk classification based on key established chromosomal abnormalities: (1) very high risk: CK, HoTr or JAK-STAT abnormalities; (2) high risk: KMT2A fusions; (3) Tyrosine kinase activating: BCR-ABL1 and ABL-class fusions; (4) standard risk: all other patients.

Risk Factors for Relapse in Acute Bacterial Prostatitis: the Impact of Antibiotic Regimens

In the manuscript, we report a large series of acute bacterial prostatitis cases and describe data about the etiology, antibiotic resistance rate, and outcome, specially focused on the risk factors for relapse. We found high rates of resistance to the most frequently used antibiotics and a high relapse rate in patients whose treatment was not adjusted according to their microbiological susceptibility.

How to investigate and manage a patient with a Staphylococcus aureus bacteraemia

Staphylococcus aureus bacteraemia is common, and associated with significant morbidity and mortality as a result of its high relapse rate and the risk of complicated infection. A positive blood culture for S. aureus should prompt a thorough patient assessment to identify a potential focus of infection, and the risk factors for the development or presence of complicated infection. Clinical management depends on the patient's characteristics and presenting features. This article gives a systematic approach to the patient with S. aureus bacteraemia, including points to look for on history and examination, the markers of complicated infection, and when to request transoesophageal echocardiography and further imaging. Treatment principles outlined include the rationale for choice of antibiotic treatment and need to involve infection specialists.

SUDMEX CONN: The Mexican MRI dataset of patients with cocaine use disorder

Cocaine use disorder (CUD) is a substance use disorder (SUD) characterized by compulsion to seek, use and abuse of cocaine, with severe health and economic consequences for the patients, their families and society. Due to the lack of successful treatments and high relapse rate, more research is needed to understand this and other SUD. Here, we present the SUDMEX CONN dataset, a Mexican open dataset of CUD patients and matched healthy controls that includes demographic, cognitive, clinical, and magnetic resonance imaging (MRI) data. MRI data includes: 1) structural (T1-weighted), 2) multishell high-angular resolution diffusion-weighted (DWI-HARDI) and 3) functional (resting state fMRI) sequences. The repository contains unprocessed MRI data available in brain imaging data structure (BIDS) format with corresponding metadata available at the OpenNeuro data sharing platform. Researchers can pursue brain variability between these groups or use a single group for a larger population sample.

Emerging Biomarkers and Therapeutic Strategies for Refractory Bullous Pemphigoid

Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering disorder in the elderly. Systemic and topical use of glucocorticoids and immunosuppressants has been shown to be effective in most patients. However, refractory BP patients are challenged to clinicians with severe clinical symptoms, resistance to treatment, and high relapse rate. How to predict and assess the refractory and severity of bullous pemphigoid is the key issue in clinical practice, and the urgent need for precision medicine in refractory patients is driving the search for biomarkers and biologics. Recently, some biomarkers, such as the level of specific autoantibodies and released cytokines, have been proposed as the potential parameters to reflect the disease severity and predict the treatment response and relapse of refractory BP. Moreover, new biologics targeting pathogenic antibodies, complement, Th2 axis, eosinophils, and Th17 axis have shown potent efficacy on refractory BP. Here, we review the literature and give an overview of emerging biomarkers and therapeutic strategies for refractory bullous pemphigoid to improve the prognosis of the patient.