Iron-based biomarkers for personalizing pharmacological ascorbate therapy in glioblastoma: insights from a phase 2 clinical trial.

BACKGROUND: Pharmacological ascorbate (intravenous delivery reaching plasma concentrations ≈ 20 mM; P-AscH-) has emerged as a promising therapeutic strategy for glioblastoma. Recently, a single-arm phase 2 clinical trial demonstrated a significant increase in overall survival when P-AscH- was combined with temozolomide and radiotherapy. As P-AscH- relies on iron-dependent mechanisms, this study aimed to assess the predictive potential of both molecular and imaging-based iron-related markers to enhance the personalization of P-AscH- therapy in glioblastoma participants. METHODS: Participants (n = 55) with newly diagnosed glioblastoma were enrolled in a phase 2 clinical trial conducted at the University of Iowa (NCT02344355). Tumor samples obtained during surgical resection were processed and stained for transferrin receptor and ferritin heavy chain expression. A blinded pathologist performed pathological assessment. Quantitative susceptibility mapping (QSM) measures were obtained from pre-radiotherapy MRI scans following maximal safe surgical resection. Circulating blood iron panels were evaluated prior to therapy through the University of Iowa Diagnostic Laboratory. RESULTS: Through univariate analysis, a significant inverse association was observed between tumor transferrin receptor expression and overall and progression-free survival. QSM measures exhibited a significant, positive association with progression-free survival. Subjects were actively followed until disease progression and then were followed through chart review or clinical visits for overall survival. CONCLUSIONS: This study analyzes iron-related biomarkers in the context of P-AscH- therapy for glioblastoma. Integrating molecular, systemic, and imaging-based markers offers a multifaceted approach to tailoring treatment strategies, thereby contributing to improved patient outcomes and advancing the field of glioblastoma therapy.

HIGHLIGHTS: Pharmacological ascorbate shows significant promise to enhance glioblastoma clinical outcomes. Transferrin receptor and ferritin heavy chain expression represent potential molecular markers to predict pharmacological ascorbate treatment response. Quantitative Susceptibility Mapping is an MRI technique that can serve as a non-invasive marker of iron metabolism to evaluate progression-free survival. Systemic iron metabolic markers are readily available diagnostic tests that can potentially be used to prognosticate overall survival.

Glycaemic control and microvascular complications among paediatric type 2 diabetes mellitus patients in Hong Kong at 2 years after diagnosis.

INTRODUCTION: Type 2 diabetes mellitus (T2DM) is becoming increasingly common among children and adolescents worldwide, including those in Hong Kong. This study analysed the characteristics and prevalence of microvascular complications among paediatric T2DM patients in Hong Kong at diagnosis and 2 years after diagnosis. METHODS: All patients aged <18 years who had been diagnosed with DM at public hospitals in Hong Kong were recruited into the Hong Kong Childhood Diabetes Registry. Data collected at diagnosis and 2 years after diagnosis were retrospectively retrieved from the Registry for patients diagnosed from 2014 to 2018. RESULTS: Median haemoglobin A1c (HbA1c) levels were 7.5% (n=203) at diagnosis and 6.5% (n=135) 2 years after diagnosis; 59.3% of patients achieved optimal glycaemic control (HbA1c level <7%) at 2 years. A higher HbA1c level at diagnosis was associated with worse glycaemic control at 2 years (correlation coefficient=0.39; P<0.001). The presence of dyslipidaemia (adjusted odds ratio [aOR]=3.19; P=0.033) and fatty liver (aOR=2.50; P=0.021) at 2 years were associated with suboptimal glycaemic control. Diabetic neuropathy and retinopathy were rare in our cohort, but 18.6% of patients developed microalbuminuria (MA) within 2 years after diagnosis. Patients with MA had a higher HbA1c level at 2 years (median: 7.2% vs 6.4%; P=0.037). Hypertension was a risk factor for MA at 2 years, independent of glycaemic control (aOR=4.61; P=0.008). CONCLUSION: These results highlight the importance of early diagnosis and holistic management (including co-morbidity management) for paediatric T2DM patients.

Whole genome sequencing of Streptococcus suis revealed potential drug resistance and zoonotic transmission in companion cat.

Streptococcus suis is a bacterium of clinical importance in diverse animal hosts including companion animals and humans. Companion animals are closely associated in the living environment of humans and are potential reservoirs for zoonotic pathogens. Given the zoonotic potential of S. suis, it is crucial to determine whether this bacterium is present among the companion animal population. This study aimed to detect Streptococcus suis in companion animals namely cats and dogs of the central west coast of Peninsular Malaysia and further characterize the positive isolates via molecular and genomic approach. The detection of S. suis was done via bacterial isolation and polymerase chain reaction assay of gdh and recN gene from oral swabs. Characterization was done by multiplex PCR serotyping, as well as muti-locus sequence typing, AMR gene prediction, MGE identification and phylogenomic analysis on whole genome sequence acquired from Illumina and Oxford Nanopore sequencing. Among the 115 samples, PCR assay detected 2/59 of the cats were positive for S. suis serotype 8 while all screened dog samples were negative. This study further described the first complete whole genome of S. suis strain SS/UPM/MY/F001 isolated from the oral cavity of a companion cat. Genomic analysis revealed a novel strain of S. suis having a unique MLST profile and antimicrobial resistance genes of mefA, msrD, patA, patB and vanY. Mobile genetic elements were described, and pathogenic determinants matched to human and swine strains were identified. Phylogenetic tree analysis on the core genome alignment revealed strain SS/UPM/MY/F001 was distinct from other S. suis strains. This study provided insight into the detection and genomic features of the S. suis isolate of a companion cat and highlighted its potential for antimicrobial resistance and pathogenicity.

Tailored treatment of female indirect inguinal hernias by using single-port laparoscopic percutaneous internal ring suture: a comparison between children and adults.

PURPOSE: To compare the outcome of indirect inguinal hernias repaired by using single-port laparoscopic percutaneous internal ring suture (SPIRS) between the pediatric and adult females. METHODS: The medical records of females who were clinically assessed to have inguinal hernia from Oct. 2016 to May 2022 were reviewed. Patients who received laparoscopy for the diagnosis of the hernia type and customized treatment according to their hernia type were included, while those who chose other operation methods initially were excluded. The patients were divided into the adult and pediatric groups based on their age. The demographic characteristics, hernia types, operation durations, and outcomes were analyzed between these two groups. RESULTS: A total of 65 adults and 60 children were included in this study. The median age was 38 years. (range: 23-88) for group A and 3 years (range: 0.1-16) for group P. Indirect hernias were present in 85% of adults and 100% of children. All the indirect hernias were repaired by SPIRS uneventfully. Incidence of contralateral patent processus vaginalis was 24% in adults and 50% in children (p = 0.016). The average operation time was 22/46 min (one/two sides) for the adults and 9/15 min (one/two sides) for the pediatrics (p < 0.010 for both). The overall complication rates were 5.4% and 3.3% for the adult and pediatric group respectively (p = 0.106). No recurrence was observed in the pediatric group, but two adults experienced recurrence and another had chronic postoperative inguinal pain, necessitating reoperation. The mean follow-up period was 38.6 ± 15.4 months for adults and 42.8 ± 18.9 months for children (p = 0.198). CONCLUSION: Our results support that the pathogenesis of indirect inguinal hernia for the female adults is due to the non-obliteration of a congenital processus vaginalis. Tailored treatment of the female IIH by using single-port laparoscopic percutaneous internal ring suture may be an alternative for the management of female IHs.

Dissemination of meticillin-resistant Staphylococcus aureus sequence type 8 (USA300) in Taiwan.

BACKGROUND: In Taiwan, sequence type (ST) 239 and ST59 were two major clones among meticillin-resistant Staphylococcus aureus (MRSA) clinical isolates in the past two decades. USA300 (ST8) prevailed in the Americas but not in outside areas. Recently USA300 (ST8) emerged and was increasingly identified in Taiwan; we thus conducted an island-wide study to explore the role of USA300 among MRSA isolates. METHODS: One hundred MRSA bloodstream isolates identified in 2020 from each of the six participating hospitals in Taiwan were collected and characterized. The first 10 ST8 isolates from each hospital were further analysed by whole-genome sequencing. RESULTS: Of the 590 confirmed MRSA isolates, a total of 22 pulsotypes and 21 STs were identified. The strain of pulsotype AI/ST8 was the most common lineage identified, accounting for 187 isolates (31.7%) and dominating in five of six hospitals, followed by pulsotype A/ST239 (14.7%), pulsotype C/ST59 (13.9%) and pulsotype D/ST59 (9.2%). Of the 187 pulsotype AI/ST8 isolates, 184 isolates were characterized as USA300 and clustered in three major sub-pulsotypes, accounting for 78%. Ninety per cent of the 60 ST8 isolates for whole-genome sequencing were clustered in three major clades. CONCLUSIONS: In 2020, USA300 became the most common clone of MRSA in Taiwan, accounting for >30% of MRSA bloodstream isolates island wide. Most of USA300 isolates circulating in Taiwan might have been imported on multiple occasions and evolved into at least three successful local clades. MRSA USA300 has successfully established its role in Taiwan, an area outside of the Americas.

Research trends of Janus Kinase inhibitors: a bibliometric and visualized study from 2012 to 2023.

OBJECTIVE: Janus Kinase (JAK) inhibitors have been extensively evaluated for their potential in the management of various diseases. Despite previous research on this topic, there is a lack of bibliometric analysis that summarizes research trends on JAK inhibitors. This study aims to provide a comprehensive overview of the top 100 most frequently cited studies on JAK inhibitors over the last ten years. MATERIALS AND METHODS: The Web of Science database was used to screen and extract relevant studies on JAK inhibitors. The top 100 studies most cited within the JAK inhibitor-related research were identified and evaluated, and various data such as the year of publication, study focus and keywords, author information, and number of citations were extracted and analyzed for further examination. RESULTS: In the top 100 most cited studies of JAK inhibitors, more than 70% of studies focused on the role of JAK inhibitors in disease treatments, with 42% of these studies focused on using JAK inhibitors as treatment for autoimmune diseases and 19 of them focused on the treatment of neoplasms. Time trend analysis revealed that the keywords "tofacitinib", "atopic dermatitis", and "rheumatoid arthritis" were widely mentioned in 2016, while new trends emerged in 2018, with "ruxolitinib" and "baricitinib" being more commonly mentioned. CONCLUSIONS: The top 100 most frequently cited studies on JAK inhibitors focused primarily on the safety and efficacy of these inhibitors in the management of various diseases, particularly inflammatory diseases and neoplasms. The results can serve as a valuable reference for rheumatologists and immunologists interested in the development of JAK inhibitors and expanding future research fields.

Is direct cardiotoxicity the primary cause of death following i. v. injection of the basic phospholipase A2 from Naja Nigricollis venom?

Con objeto de elucidar la función del Ca intracelular en la transmisión neuromuscular investigamos en preparaciones de músculo de rana los efectos del ácido1,2-bis(o-aminofenoxi)etano-N,N,N',N'-tetraacético (BAPTA) sobre el aumento-potenciación por frecuencia (anteriormente llamado facilitación por frecuencia) el que ha sido de utilidad para identificar los sitios de acción de varios agentes colinérgicos. La disminución de los iones Ca del espacio intracelular por BAPTA sólo suprimió el componente dependiente de Ca del fenómeno (ma) sin modificar el factor de estimulación dependiente de frecuencia (K). La depresión causada por BAPTA en la facilitación de corto plazo del potencial de placa (EPP) fue la misma tanto en reposo como en la estimulación. El efecto del BAPTA fue parcialmente antagonizado, por el ionóforo de Ca A23187. Esto sugiere que la capacidad de "buffer" de Ca del BAPTA se mantiene durante la estimulación repetitiva de baja frecuencia. BAPTA no modificó la potenciación post-tetánica de los EPP miniatura en medio libre de Ca. Estos resultados indican que los iones Ca son esenciales para la liberación de transmisor y para la facilitación de corto plazo, pero no son responsables de todos los cambios en la liberación de transmisor