Staging Criteria Research Articles

Biomarker-only diagnosis of Alzheimer's disease: Not ready for prime time.

The Alzheimer's Association Workgroup research criteria for diagnosis and staging of Alzheimer's disease hypothesize diagnostic meaning in the absence of clinical symptoms. If operationalized, this would trivialize neuropsychological assessment but would also expand the pool of candidates for anti-amyloid therapies. A recent survey of the reactions of clinical neuropsychologists to these criteria suggested that the purpose lacked clarity, among other concerns. Given the current landscape in Alzheimer's disease therapeutics, with substantial toxicity and unclear benefit, as well as the poorly understood relationships between biomarkers and clinical signs at the individual level, the roll out of biomarker-only disease seems premature.

Microvesicle Tissue Factor Procoagulant Activity Is Elevated and Correlated With Disease Severity in Patients With Cirrhosis.

Tissue factor-expressing microvesicles (MV-TF) have been found to correlate with thrombotic complications in various diseases. Simultaneously, there is expanding research regarding the effect of the coagulation cascade on liver fibrosis progression. The aim of our manuscript was to evaluate MV-TF activity in patients with cirrhosis and its correlation with disease severity. We prospectively enrolled 82 patients [11 with cirrhosis and hepatocellular cancer (Group 1), 50 with cirrhosis (Group 2) and 21 controls (Group 3)]. Extensive workup for disease staging and exclusion criteria was undertaken. Exclusion criteria included thrombophilia, history of thrombosis, recent hospitalisation, ongoing infection, alcohol dependence, cancer, haematological diseases and use of anticoagulant, antiplatelet or contraceptive drugs. Plasma tissue factor antigen concentration and MV-TF activity were assessed. MV-TF showed median values of 4.03 [1.57], 3.17 [1.59] and 2.26 [1.23] pg/mL in Groups 1, 2 and 3, respectively. There was a statistically significant difference between Groups 1 and 3 (p < 0.001) and Groups 2 and 3 (p = 0.003), while Group 1 had higher values than Group 2 without statistical significance (p = 0.088). In Group 2, the patients' Child-Pugh (CP) stage was A in 56%, B in 26% and C in 18% of cases. MV-TF activity significantly correlated with decompensated cirrhosis (p = 0.005) and higher CP stage (p = 0.011). Finally, MV-TF activity significantly correlated with 12-month mortality (p = 0.021). MV-TF activity is elevated in patients with cirrhosis, showing a significant correlation with disease severity. MV-TF may play a role in the procoagulant imbalance of liver cirrhosis and their contribution in disease progression should be studied further.

Gastroesophageal varices in primary biliary cholangitis with anti-centromere antibody positivity: Early onset?

Primary biliary cholangitis (PBC) is an autoimmune liver disease. During the diagnostic process, the patient's autoimmune antibodies are routinely examined. Approximately 20% of PBC patients have positive anti-centromere antibody (ACA). We evaluated the clinical characteristics of ACA-positive and ACA-negative PBC patients to explain the differences in disease progression between these two groups. Retrospective data from 961 PBC patients at Beijing Youan Hospital from 2010 to 2019 were gathered and separated into two groups based on ACA positivity. We collected and evaluated clinical laboratory indices, gastroscopy findings, and liver function assessments. In addition, 60 liver biopsies were available for comparison between the 2 groups. Pathologists staged the histological findings using the Ludwig staging criteria and Nakanuma staging and grading. Immunohistochemical staining was also performed on liver biopsies to examine the expression of cytokeratin 7 (CK7) in the tissue. A synthesis of clinical indicators in the large cohort showed that alanine transaminase, aspartate aminotransferase, total bilirubin, IgG, white blood cell, and platelet were significantly lower in the ACA-positive group, indicating that the overall status of liver injury was more moderate in the ACA-positive group. Additionally, ACA-positive patients in the non-cirrhotic group were more likely to present with gastroesophageal varices related to portal hypertension. Finally, analysis of pathologic findings showed that parameters were mostly comparable in the two groups, but CK7 differed and was more significantly lower in the ACA-positive group in albumin-bilirubin grade 2 and 3 patients. In summary, we characterized and compared the clinical features of ACA-positive and ACA-negative PBC patients, corroborating previous studies on the relationship between ACA positivity and portal hypertension cross-sectionally. It suggested that gastroesophageal varices might happen in the earlier course of PBC natural progression in the ACA-positive group.

Risk Factors for Necrotizing Enterocolitis in Very Low Birth Weight Infants in a Tertiary Care Hospital

Background: Necrotizing enterocolitis (NEC) is a severe gastrointestinal condition correlated with increased morbidity and mortality in very low birth weight (VLBW) infants. The pathophysiology of NEC remains elusive due to its multifactorial nature. However, the identification and prevention of significant factors that cause NEC can improve the outcome of these neonates. Objective: To identify factors associated with the development of definite NEC, based on the modified Bell staging criteria stage II and III, in VLBW infants in a setting of tertiary care hospital. Materials and Methods: A single-center, case-control study was conducted in VLBW infants who were admitted to the neonatal intensive care unit (NICU) of Bhumibol Adulyadej Hospital, Bangkok, Thailand, between January 2008 and December 2022. Clinical data were collected from the electronic medical records. For each case of NEC, two controls without NEC, as non-NEC, were matched based on gestational age and period of hospitalization in the department. Data of mothers, infants, feeding patterns, and comorbidities prior to the diagnosis of NEC were analyzed. Results: There were 65 and 130 infants in the NEC and the non-NEC group, respectively. Infants in both groups had similar baseline characteristics. Multiple logistic regression showed the amount of human milk at the age of 14 days (adjusted OR 0.08, p&lt;0.001) was a protective factor against NEC. Conversely, prolonged parenteral nutrition (PN) use (adjusted OR 4.81, p&lt;0.001) and septic shock (adjusted OR 4.36, p=0.02) were risk factors for NEC. Conclusion: Early initiation of human milk may reduce the incidence of NEC. On the other hand, infants requiring extended PN and suffering septic shock were at an increased risk of developing NEC.

Challenges in a Biological Definition of Alzheimer Disease.

It has been suggested that the diagnostic landscape of Alzheimer disease (AD) is undergoing a profound transformation, marked by a shift toward a biomarker-based approach, as proposed by the Revised Criteria for Diagnosis and Staging of Alzheimer's Disease. These criteria advocate for diagnosing AD solely on biomarkers, without requiring clinical symptoms. This article explores the drivers behind this transition, primarily influenced by the Food and Drug Administration's approval of amyloid-lowering treatments. We evaluate the proposed criteria, which allow for an AD diagnosis based on amyloid "A" or phosphorylated tau "T1" positivity through surrogate amyloid PET imaging, CSF, or plasma biomarkers, and consider the arguments for and against their use. The merits of the new criteria include a clearer definition of AD, which is currently used interchangeably to refer to both the presence of neuropathology and the clinical syndrome. We argue that a purely biological definition risks a category error and emphasize the need for longitudinal data to establish the lifetime risk of dementia in amyloid-positive and tau-positive individuals. We also caution against limiting the scope of biomarker-based AD diagnosis to amyloid and tau alone. In conclusion, we recommend that the criteria remain within the research domain for the present while advocating for the considered adoption of plasma biomarkers in clinical practice.

The prevalence of chronic traumatic encephalopathy in a historical epilepsy post-mortem collection.

Previous post-mortem epilepsy series showed phosphorylated tau (pTau) accumulation in relation to traumatic brain injury (TBI) rather than driven by seizure frequency. The Corsellis Epilepsy Collection, established in the mid-20th century, represents brain samples collected from patients living with a range of epilepsies from the 1880s to 1990s. Our aim was to interrogate this historical archive to explore relationships between epilepsy, trauma and tau pathology. AT8 immunohistochemistry for pTau was carried out in 102 cases (55% male, with mean age at death of 62 years) on frontal, temporal, amygdala, hippocampal and lesional cortical regions and evaluated using current NINDS criteria for chronic traumatic encephalopathy (CTE) and Braak staging with beta-amyloid, AT8-GFAP and other pTau markers (CP13, PHF1, AT100, AT180) in selected cases. CTE-neuropathologic change (CTE-NC) was identified in 15.7% and was associated with the presence of astroglial tau, a younger age of onset of epilepsy, evidence of TBI and institutionalisation for epilepsy compared to cases without CTE-NC, but not for seizure type or frequency. Memory impairment was noted in 43% of cases with CTE-NC, and a significantly younger age of death; more frequent reports of sudden and unexpected death (p <0.05-0.001) were noted in cases with CTE-NC. In contrast, a higher Braak stage was associated with late-onset epilepsy and cognitive decline. Of note, 9% of cases showed no pTau, including cases with long epilepsy duration, poor seizure control and a history of prior TBI. In summary, this cohort includes patients with more severe and diverse forms of epilepsy, with CTE-NC observed more frequently than reported in non-epilepsy community-based studies (0%-8%) but lower than published series from contact sports participants (32%-87%). Although the literature does not report increased epilepsy occurring in CTE syndrome, our findings support an increased risk of CTE in epilepsy syndromes, likely primarily related to increased TBI.

Clinical application of oral contrast-enhanced ultrasound in evaluating the preoperative T staging of gastric cancer.

Oral contrast-enhanced ultrasound (OCEUS) is widely used in the noninvasive diagnosis and screening of gastric cancer (GC) in China. To investigate the clinical application of OCEUS in evaluating the preoperative T staging of gastric cancer. OCEUS was performed before the operation, and standard ultrasound images were retained. The depth of infiltration of GC (T-stage) was evaluated according to the American Joint Committee on Cancer 8th edition of the tumor-node-metastasis staging criteria. Finally, with postoperative pathological staging as the gold standard reference, the sensitivity, specificity, negative predictive value, positive predictive value, and diagnostic value of OCEUS T staging were evaluated. OCEUS achieved diagnostic accuracy rates of 76.6% (T1a), 69.6% (T1b), 62.7% (T2), 60.8% (T3), 88.0% (T4a), and 88.7% (T4b), with an average of 75.5%. Ultrasonic T staging sensitivity exceeded 62%, aside from T1b at 40.3%, while specificity was over 91%, except for T3 with 83.5%. The Youden index was above 60%, with T1b and T2 being exceptions. OCEUS T staging corresponded closely with pathology in T4b (kappa > 0.75) and moderately in T1a, T1b, T2, T3, and T4a (kappa 0.40-0.75), registering a concordance rate exceeding 84%. OCEUS was effective, reliable, and accurate in diagnosing the preoperative T staging of GC. As a noninvasive diagnostic technique, OCEUS merits clinical popularization.

Assessment of Optimal Treatment Strategies and Their Outcomes in T3N1 Rectal Cancers.

Background:This study compares the outcomes of a surgery first vs a neoadjuvant treatment strategy in T3N1M0 rectal cancers. Methods:This was a single-centre retrospective cohort study of patients admitted for curative treatment of T3N1 rectal cancer. Patients with pre-treatment T3N1 and pathological T3N1 disease were included in the study. Patients were divided into two groups depending on whether they had surgery or neoadjuvant therapy as their initial phase of treatment. Primary outcome measures were local recurrence and distant recurrence. Secondary outcomes were disease-free survival (DFS) and overall survival (OS). Tabulated results were analyzed with appropriate statistical tests. Results:One hundred and ten patients were initially selected. Fourty-eight were finally included after excluding patients who did not meet the staging criteria or were not eligible for curative treatment. Twenty-nine patients underwent surgery, and 19 patients with neoadjuvant therapy as their first treatment. No local recurrence was noted in either group, with a distant recurrence noted in group 2 (6.9%) and group 1 (5.26%) cases among the surgery-first and neoadjuvant-first groups, respectively. Disease-free survival and overall survival were 29.5 and 30 months for the surgery-first group and 22 and 22 months for the neo-adjuvant group, respectively. Conclusions:Outcomes in the surgery-first group were non-inferior to that of the neoadjuvant group. A threatened circumferential resection margin (CRM) on pretreatment staging warrants neoadjuvant therapy to ensure an R0 resection. Extramural vascular invasion (EMVI), being a negative prognostic factor, doesn't preclude a surgery-first approach.

Characteristics of the hydrological regime of the periglacial moraine lakes in the Altai

In the last decade glaciers of Inner Asia have been shrinking with acceleration, and the number of glacial lakes has been growing significantly, including those with a high probability of outburst and high-water discharge. The hydrological regime of lakes in the Altai is understudied in comparison with lakes in other high mountain countries. The article is based on our extensive field material on hydrological and morphometric characteristics of moraine lakes collected in the Russian and Mongolian parts of the Altai Mountains and combined with the Earth remote sensing data. We have proposed detailed indicators (criteria) of transgressive, regressive and post-regressive stages of lake development. It allows allow to determine at a qualitative level at what stage a lake is at and to assess its further development. The characteristics of hydrological regime of Altai lakes at different stages of development are described for the first time. Based on the criteria proposed, the classification of glacial and moraine lakes in the Altai high mountains was carried out. It shows that at present most of the lakes are in the transgressive stage. Over the last 22 years, the number of lakes has increased significantly: on the territory of the North Chuya Ridge – from 28 to 60, on the South Chuya Ridge – from 39 to 73, on the Katun Ridge – from 57 to 89, on the territory of the Tavan-Bogdo-Ola massif – from 11 to 19, and on the territory of the Mongun-Taiga massif – from 8 to 11 lakes.

Pharmaceutical quality of dispersible diclofenac tablets in the Saudi market

The fundamental objective in developing any drug delivery approach is to achieve effective and safe therapy. Medications classified as generics are those that contain the same active ingredients and have the same quality as the reference medications. Several generic drugs are available on the market, all at a reasonable cost. In this study, the quality of Three generic brands of diclofenac dispersible tablets available in the Saudi market was assessed, namely: G1 and G2, and G3.Except for the borderline performance of one generic formulation (G3), all formulations passed in vitro quality tests according to the United States Pharmacopoeia. According to the US Pharmacopoeia, every generic formulation passed in vitro quality tests, except for one generic formulation (G3) that performed inconclusively. All brands showed low weight variation, minimum weight loss in the friability test, and a rapid dispersion time of around 5 s. The chemical potency results demonstrated that all three brands complied with United States Pharmacopeia (USP) specifications, typically falling between 90% and 110% of the labeled amount. G1 and G2 passed the content uniformity test in their first attempt. G3 initially failed the content uniformity test but passed upon retesting with additional samples. G1 and G2 tablets passed the USP Acceptance criteria in stage one, and G3 tablets met the requirements in stage two. G1 showed the highest DE (%78.83), followed by G2 (%72.23), and G3 (%67.50). The G1 dissolution data, which showed the highest dissolution efficiency, were used as the reference product to calculate the similarity factor (f2 (ratio. G1 (Reference) and G2 with an f2 of (58.3) have similar dissolution profiles, however, the dissolution profiles for the two products may be considered similar without f2 calculation since more than 85% of the drug was dissolved within 15 min (SFDA Guidelines for Bioequivalence, Similarity while G3, with an f2 of (47.5) suggest a lack of similarity between the two dissolution profiles. This study highlights the importance of post-marketing evaluations of generic drug performance.

Association between perioperative platelet distribution width changes and postoperative acute kidney injury in patients with renal insufficiency: a retrospective study

BackgroundAcute kidney injury (AKI) is a major complication following cardiac surgery with a high incidence in those with existing kidney dysfunction. Platelet distribution width (PDW) reflects variability in platelet size and serves as an indicator of platelet activation. Recent investigations linked PDW changes to kidney pathology, suggesting its utility in identifying individuals at risk for AKI, thus necessitating exploration of its predictive value.MethodsPatients with preoperative renal dysfunction [15 ≤ estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73m2] who underwent cardiac surgery from January 2018 to December 2021 were retrospectively enrolled. PDW values were measured preoperatively and again upon admission to the ICU immediately after cardiac surgery, with the change in PDW (dPDW) defined as the difference between these two measurements. The primary outcome was postoperative AKI, defined base on the Kidney Disease: Improving Global Outcomes (KDIGO) definition and staging criteria. Multivariate regression models were performed to identify the association between dPDW and AKI and its potential trend. Restricted cubic spline analysis assessed non-linear associations between dPDW and AKI. The Youden index identified an optimal dPDW cut-off for AKI prediction. Subgroup analysis was performed to elucidate the consistency of these associations across the various subgroups.ResultsAKI occurred in 53.10% (513/966) of patients, accompanied by significant PDW increases in cases of AKI (P < 0.001). After adjusting confounders, dPDW was identified as a significant risk factor for AKI [odds ratio (OR) = 1.09, 95% confidence interval (CI): (1.02 ~ 1.16), P = 0.012]. Patients in the highest dPDW quartile (Q4) had a 195% higher AKI risk compared to those in the lowest quartile (Q1) (OR = 2.95, 95% CI:1.78 ∼ 4.90, P < 0.001). Trend analysis indicates that the risk of AKI increased with higher dPDW quartiles (P for trend < 0.001). Youden index showed that dRDW = 1.1 was identified as the optimal diagnostic cut-off value for AKI. Subgroup analyses and interaction tests showed a robust association between dPDW and AKI in all subgroups (P for interaction > 0.05).ConclusionsThis study underscored perioperative PDW changes as a significant predictor of postoperative AKI in patients with renal insufficiency, highlighting its potential in refining risk stratification and management strategies.Clinical trial numberNot applicable for this observational retrospective study.

Impact of FIGO 2023 staging criteria for endometrial cancer on stage migration and survival outcomes

Impact of FIGO 2023 staging criteria for endometrial cancer on stage migration and survival outcomes

A multivariable disease specific model enhances prognostication beyond current Merkel cell carcinoma staging: an international cohort study of 10,958 patients.

BackgroundMerkel cell carcinoma (MCC) is a highly aggressive cutaneous malignancy for which accurate prognostication is necessary to support clinical management. Objective1. To determine which survival endpoint - disease-specific-death (DSD) or overall survival (OS)- was better stratified by MCC AJCC 8th edition staging. 2. To develop a multivariable model for enhanced MCC survival predictions. MethodsRetrospective analysis of 10,958 histologically confirmed MCC between January 2000 and December 2020 was performed. Patient and tumor features were analysed from two cohorts: a US cohort and an external validation UK cohort. A multivariable Fine and Gray Competing Risk (FG) model was utilised to account for competing risk. ResultsDSD demonstrated greater discriminatory power as a survival endpoint when compared to OS. Multivariate FG analysis identified the most impactful features for DSD: truncal lesions (subdistribution hazard ratios (SHR) 1.96, p<.001), age >84 years (SHR 1.79, p<.001), male sex (SHR 1.34, p<.001) and marital status (SHR 1.09, p<.001). A second FG model incorporating those impactful features enhanced survival predictions beyond current MCC staging criteria alone in both US (C-index 0.75 vs 0.64, p<.001) and external validation cohorts. cohort (C-index 0.77). ConclusionsMCC staging can stratify DSD better than OS. Additional patient and tumour features enhanced prognostication beyond current staging systems.

Association between heart failure in asymptomatic stages and skeletal muscle function assessed by ultrasonography in community-dwelling older adults

BackgroundSymptomatic heart failure (HF) negatively affects the quantity and quality of skeletal muscles. However, the association between asymptomatic HF and skeletal muscle function remains unclear. We aimed to use ultrasonography to elucidate the association between asymptomatic HF and skeletal muscle function in community-dwelling older adults.MethodsThis cross-sectional study comprised community-dwelling older adults aged ≥ 60 years who could perform activities of daily living independently and had never had symptomatic HF (n = 52, 76.3 ± 6.1 years). The participants were classified into three groups namely, non-HF (n = 26), stage A (n = 19), and stage B (n = 7) according to the HF stage criteria of the American Heart Association /American College of Cardiology /Heart Failure Society of America guideline. Skeletal muscle quantity and quality were assessed using ultrasonography (thickness and echo intensity) of the rectus femoris (RF) and vastus intermedius (VI) muscles. The group effects on muscle thickness and echo intensity in each group were assessed using a multivariate analysis.ResultsBoth muscles consistently demonstrated significant group effects on the thickness and echo intensity. Thicknesses of the RF (p = 0.020) and VI (p = 0.035) were lower in the stage B group than that in the non-HF group. The echo intensities in the RF (p = 0.006) and VI (p = 0.009) were higher in the stage B group than that in the non-HF group.ConclusionAsymptomatic HF negatively associated with the characteristics of skeletal muscle function, as assessed by ultrasonography in community-dwelling older adults. The stage B HF contributes to reduced skeletal muscle function as well as symptomatic HF.

Absence of Kidney Tubular Injury in Patients With Acute Heart Failure With Acute Kidney Injury.

Worsening renal function (WRF) is common in hospitalized patients being treated for acute heart failure. However, discriminating clinically significant WRF remains challenging. In patients hospitalized with acute heart failure, we evaluated if blood and urine biomarkers of cardiac and kidney dysfunction were associated with adverse outcomes. We identified 175 of 927 participants in the AKINESIS study (Acute Kidney Neutrophil Gelatinase-Associated Lipocalin Evaluation of Symptomatic Heart Failure Study) who met criteria for stage 1 or 2 Kidney Disease: Improvement Global Outcomes acute kidney injury during the first 3 days of hospitalization. We measured 24 blood and urine biomarkers from specimens collected within 24 hours of meeting acute kidney injury criteria. The primary composite outcome consisted of worsening WRF (higher acute kidney injury stage), need for dialysis, or death at 30 days. Biomarkers' association with the composite outcome was assessed with logistic regression by tertiles and area under the curve (AUC). Of the 175 participants, 32 (18%) developed the primary composite outcome. Only history of chronic kidney disease was significantly different between those with and without the composite outcome. The highest tertile of plasma Gal-3 (galectin-3) and urine epidermal growth factor were associated with increased odds of the composite outcome compared with the lowest tertile in unadjusted analyses. After adjusting for serum creatinine, systolic blood pressure, and blood urea nitrogen, only the highest tertile of Gal-3 was associated with greater odds of the composite outcome (odds ratio, 4.6 [95% CI, 1.4-16.0). Gal-3 had the highest AUC (0.70 [95% CI, 0.58-0.82]), while epidermal growth factor had a lower AUC (0.63 [95% CI, 0.53-0.74]). Notably, urine biomarkers of kidney tubule injury were not associated with the composite outcome. Tubular injury does not occur in most patients with acute heart failure experiencing WRF, consistent with the functional mechanisms of WRF in this patient population. URL: https://www.clinicaltrials.gov/study/NCT01291836?term=NCT01291836&rank=1; Unique identifier: NCT01291836.

Incremental eligibility criteria for the BMT CTN 1507 haploidentical trial for children with sickle cell disease

AbstractThe Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 1507 leadership and the data safety monitoring board (DSMB) established incremental entry criteria for children aged 5 to 14.99 years with sickle cell disease (SCD) enrolling in a phase 2 trial of HLA-haploidentical hematopoietic stem cell transplantation. First, the enrollment was limited to overt stroke in the first 10 participants (stage 4). Subsequently, the DSMB reviewed the interim results and expanded the eligibility to include children with silent cerebral infarcts or abnormal transcranial Doppler velocities with magnetic resonance angiography–defined cerebral vasculopathy (stage 3). A third cohort was enrolled after the DSMB reviewed the clinical outcomes in these cumulative initial enrollments (n = 18) and additions were made to the entry criteria that included nonneurologic morbidities (stage 2). Added eligibility criteria included the following: (1) life-threatening acute chest syndrome requiring exchange transfusion; (2) right heart catheterization confirmed pulmonary hypertension; (3) persistent systemic hypertension despite maximum medical therapy; (4) acute pain despite maximum medical therapy in the absence of psychosocial factors and unmanaged asthma after adjudication; and (5) 2 major priapism episodes in 12 months or 3 in 24 months. Children with SCD who did not meet the criteria for stages 4, 3, and 2 were not eligible. To our knowledge, for the first time, we introduce a staged strategy for eligibility in a curative therapy trial for children with SCD concordant with 45 Code of Federal Regulations § 46.405(b). The research governance–mandated eligibility strategy used within the BMT CTN 1507 phase 2 study may apply to future pediatric SCD curative therapy trials. This trial was registered at www.ClinicalTrials.gov as #NCT032635590.

Sepsis associated acute kidney injury is common among Aboriginal and Torres Strait Islanders with septic shock and has poor outcomes: A nested cohort study.

Exploration of the incidence and outcomes of Acute Kidney Injury (AKI) broadly, and sepsis associated AKI specifically, in Aboriginal and Torres Strait Islander (First Nations) people has been limited. We compared a nested cohort of First Nations people drawn from a multinational randomised controlled trial of hydrocortisone in septic shock, to a cohort matched for age, sex and severity of illness. Acute Kidney Injury was defined using the Kidney Disease Improving Global Outcomes (KDIGO) criteria, as well as incident use of kidney replacement therapy (KRT). Major Adverse Kidney Events (MAKE) were described as the composite of death, new dialysis requirement or persisting kidney dysfunction at hospital discharge. A cohort of 57 Aboriginal and/or Torres Strait Islander patients with septic shock was identified. 91.2% (52) of the First Nations cohort met KDIGO criteria for Stage 1 AKI or greater and 63% (36) met Stage 3 criteria. 59.6% (34) of the First Nations required dialysis as compared to 45.6% (26) in the matched cohort. 60.7% (34) of First Nations participants met criteria for MAKE at hospital discharge. The proportions requiring dialysis at 6, 12 and 24 months were 8.3%, 9.1% and 6.9% respectively. The incidences of AKI and MAKE reported in this First Nations cohort are substantially higher than in previously published cohorts of patients with sepsis, even those that use sensitive definitions of AKI. Measures to promote better management of infectious diseases in First Nations communities are required.

Relationship between serum level of miR-338-3p and miR-105-3p and bone metabolic markers in patients with diabetes nephropathy

Objectives Diabetic nephropathy (DN) is one of the most common and serious complications of diabetes. The purpose of this study was to explore the relationship between serum microRNA-338-3p (miR-338-3p) and miR-105-3p and bone metabolic markers in patients with DN at different stages. Methods A total of 153 patients diagnosed and treated in the Department of Nephrology from July 2020 to October 2021 were selected as the study objects. According to the staging criteria of diabetic nephropathy and 24-h urinary albumin quantitative level, the patients were divided into control group (35 cases), microalbuminuria group (37 cases), clinical stage albuminuria group (27 cases) and renal failure group (54 cases). Gene expressions were measured by real-time fluorescence quantitative PCR. The correlation was analyzed by Spearman. Serum miR-338-3p and miR-150-5p in the prediction of renal failure in DN was analyzed by ROC curve. Results The levels of urinary albumin and serum creatinine were markedly increased with the increase of DN stage (p < 0.05). Compared with the microalbuminuria group, the expression levels of serum miR-383-3p, serum miR-105-3p, 25(OH)-D, BGP and PINP were obviously decreased, but the expression of parathyroid hormone (PTH) and type I collagen (β-CTX) was largely increased in clinical proteinuria group (p < 0.05). Compared with the clinical proteinuria group, the expression levels of serum miR-383-3p, serum miR-105-3p, 25(OH)-D, BGP and PINP were largely decreased, but the expression of PTH and β-CTX was obviously increased in the renal failure group (p < 0.05). Spearman correlation results showed that serum expressions of miR-383-3p and miR-105-3p were negatively correlated with PTH and β-CTX, and positively correlated with 25(OH)-D, BGP and PINP (p < 0.05). ROC curve analysis showed that the AUC of serum miR-338-3p and miR-150-5p was 0.896 with the specificity and sensitivity of 96.66% and 73.47%, which had certain predictive value for the occurrence of renal failure in DN. Conclusions The expression levels of serum miR-383-3p and miR-105-3p were significantly correlated with bone metabolism markers. The combined test can provide new ideas and insights for the clinical treatment of osteoporosis in DN.

A Review of Surgical Outcomes of Management of Sinonasal Malignancies: A 8-Year of Clinical Experience (2013-2021) at the Tertiary Centre, Sarawak.

Sinonasal carcinoma, a rare and challenging malignancy, originating in the nasal cavity and paranasal sinuses, poses diagnostic and management complexities. This 8-year retrospective analysis at Sarawak General Hospital aims to elucidate demographic trends, histopathological entities, and management outcomes, shedding light on this multifaceted malignancy. Emphasizing the significance of accurate histopathological classification, the study explores the impact on prognostication and treatment strategies. Spanning 2013 to 2021, the study involved 54 patients with sinonasal malignancies. Demographic, clinical, and histopathological details were examined, adhered to the AJCC staging criteria. Analysis involved demographic distributions, tumour characteristics, treatment modalities, and instances of treatment failure. Statistical analysis was done using SPSS version 29.02. The cohort, predominantly male (57.4%) and of Iban ethnicity (44.4%), with a mean age of 52.8 years, exhibited diverse histopathologies, with squamous cell carcinoma as the most common (38.9%). Epistaxis and nasal blockage were common clinical presentations. Advanced stages (III and IV) were prevalent, with the nasal cavity as the primary site. Surgical interventions, mainly endoscopic endonasal excision, were complemented by adjuvant therapies. Complications occurred in 24% of cases. The study highlights a male predilection, occupational risk factors, and a significant association between tobacco smoking and sinonasal cancers. Surgical interventions predominantly utilized the endoscopic approach. Despite a mean survival of 46.6 months, treatment failure occurred in 29.6% of cases, with recurrence and metastasis. Histopathological analysis revealed comparable 5-year disease survival rates between squamous and non-squamous histologies. Treatment failure was significantly associated with the mode of surgery, with open surgery showing a lower incidence. However, nodal status, histopathology types, T staging, and overall staging did display positive associations with treatment failure. This 8-year review provides comprehensive insights into sinonasal carcinoma, addressing demographic, clinical, and histopathological dimensions. The study underlines the complexity of managing this challenging malignancy, emphasizing the need for a holistic approach to patient care. The findings contribute to the understanding of sinonasal carcinoma, guiding clinical decision-making and fostering further research.

The new FIGO 2023 staging reclassification of patients with FIGO 2009 Stage IVB endometrial cancer correlates to progression-free and overall survival outcomes

ObjectiveThis study aims to determine the oncological outcomes of Stage IVB (FIGO 2009) Endometrial cancer patients and its comparison with the new (FIGO 2023) staging. MethodsA Retrospective analysis was conducted between May 30, 2011, and December 30, 2020 on all patients with stage IVB (FIGO 2009 Staging) endometrial cancer. Overall survival (OS) was the primary outcome. Progression-Free Survival (PFS) and comparison with new staging FIGO 2023 were the secondary outcomes. Kaplan-Meier curves and log-rank tests were used to compare the average OS time and PFS between the groups. ResultsFifty-one patients with Stage IVB endometrial cancer (2009 FIGO Staging) were included. Median age was 68 years. Serous histology was found in 24 (47.1 %) patients. After a median follow-up period of 24 months, median OS was 36 months and median PFS was 15 months. FIGO 2023 staging criteria reclassified the stages of 23 patients (45 %). Patients were restaged into Stage IIIB2 (9.8 %), IVA (5.8 %), IVB (55 %) and IVC (29.4 %). Median OS and PFS were not reached for stages IIIB and IVA, while the median OS and median PFS for stage IVB were 36 months and 18 months, respectively. However, patients with stage IVC had lower median OS and PFS of 10 months and 4 months, respectively. ConclusionThe clinical outcomes of patients with Stage IVB are varied depending mainly on the disease distribution. Patients with abdominal or pelvic disease had better survival outcomes and therefore, needed a different categorisation. Thus, FIGO 2023 Staging considers this varied disease distribution and appears to be a better prognostic indicator for this group.