Alzheimer\'s disease (AD) research has been dominated by the single-factor amyloid hypothesis in the last decades. Several other hypotheses have been proposed and increasingly attract attention considering the limited success of amyloid-based therapeutic strategies. Surprisingly, most published alternative etiological hypotheses for AD are similarly single-factor hypotheses, such as vascular, metabolic, mitochondrial, infectious, and inflammatory hypotheses, but the existence of so many different hypotheses suggests that AD is most likely a complex, multifactorial disorder. This inventory of different etiological hypotheses will hopefully help the field to move forward with explanatory models that consider the multifaceted aspects of this devastating disorder.

Alzheimer\'s disease (AD) is a serious dementia afflicting aging population and is characterized by cognitive decline, amyloid-β plaques, and neurofibrillary tangles. AD substantially impairs the life quality of the victims and poses a heavy burden on the society at large. The number of people with dementia due to AD, prodromal AD, and preclinical AD is estimated to stand at roughly 3.2, 69, and 315 million worldwide, respectively. Current clinical diagnosis is based on clinical symptoms, and clinical research demonstrated that positron emission tomography (PET) and cerebrospinal fluid (CSF) biomarkers had excellent diagnostic performance. However, the application of CSF biomarker tests and PET are restricted by the invasiveness and high cost. The presence of clinical symptoms means that AD pathology has been progressing for many years, and only a few drugs have been approved for the traetemnt of AD. Therefore, early diagnosis is extremely important for controlling the outcomes caused by AD. In this review, we provided an overview of developing clinical diagnostic criteria, diagnostic strategies under clinical research, developing blood based-biomarker assays, and promising nanotechnologically-based assays.

UNASSIGNED: No established definition for early-stage knee osteoarthritis (KOA) is available, nor classification criteria. Identifying the characteristics of individuals presenting with early-stage KOA symptoms can enhance diagnosis to prevent progression. This study aimed to describe clinical and structural features of individuals presenting with knee complaints within two years after their first consultation, while exploring differences in the duration of knee complaints.
UNASSIGNED: Baseline data was used from the LITE randomized controlled trial, assessing the effectiveness of a lifestyle intervention for individuals with knee complaints and overweight in primary care. Baseline assessments included questionnaires, clinical assessment, and MRI of the most symptomatic knee. Differences between groups with varying durations of knee complaints (<12, ≥12-<24, ≥24 months) were evaluated.
UNASSIGNED: Participants (N ​= ​218, 65% female, mean age 59 ​± ​6 years, mean BMI 32 ​± ​5 ​kg/m2) had a median knee complaint duration of 14 months, with an average KOOS pain score of 60 ​± ​17.46% reported their symptoms as unacceptable. Structural MRI-defined KOA was observed in 71% of participants. There were no significant differences in clinical or structural MRI features between different durations of knee complaints.
UNASSIGNED: Within 24 months of initial consultation, over two-thirds of participants displayed MRI-defined structural KOA, and nearly half reported unacceptable symptom states. This study found no association between the duration of knee complaints and symptoms severity or structural KOA presence, underscoring the complexity of identifying stages of KOA among individuals with overweight. Future studies should explore additional features beyond current considerations to facilitate early-stage KOA diagnosis, specifically for individuals with overweight.

A decade after International Myeloma Working Group (IMWG) biomarkers (SLiM criteria) were introduced, this real-world study examined their impact on diagnosis, therapy and outcomes in myeloma. Using the ANZ MRDR, 3489 newly diagnosed patients from 2013 to 2023, comprising 3232 diagnosed by CRAB (\'CRAB patients\', including 1758 who also satisfied ≥1 SLiM criteria) and 257 by SLiM (\'SLiM patients\') criteria were analysed. CRAB patients had higher R-ISS and lower performance status, with no difference in cytogenetic risk. SLiM patients had improved progression-free survival (PFS, 37.5 vs. 32.2 months, hazard ratio [HR] 1.31 [1.08-1.59], p = 0.003), overall survival (80.9 vs. 73.2 months, HR 1.64 [1.26-2.13], p < 0.001) and PFS2 (54.6 vs. 40.3 months, HR 1.51 [1.22-1.86], p < 0.001) compared with CRAB patients, partially explained by earlier diagnosis, with no differential impact between the plasma cell and light-chain criteria on PFS. However, 34% of CRAB patients did not manifest SLiM characteristics, raising the possibility that SLiM features are associated with different biological behaviours contributing to a better prognosis, for example, improved PFS2 in SLiM patients suggested less disease resistance at first relapse. These data support earlier initiation of therapy by SLiM. The superior survival outcomes of SLiM versus CRAB patients highlight the importance of defining these subgroups when interpreting therapeutic outcomes at induction and first relapse.

OBJECTIVE: The ESPEN and the EASO recently developed consensus criteria for sarcopenic obesity (SO), employing the skeletal muscle mass to weight (SMM/W) ratio. Emerging evidence suggests that adjusting skeletal muscle mass for body mass index (SMM/BMI) could enhance the predictive accuracy for health outcomes. We aimed to validate the ESPEN/EASO criteria and explore the potential benefits of the SMM/BMI adjustment in predicting falls among older adults in Western China.
METHODS: We conducted a multicenter, cross-sectional study and included community-dwelling older adults. The diagnosis of SO was determined using the standard ESPEN/EASO consensus criteria (SOESPEN) and a modified version adjusting SMM/BMI (SOESPEN-M). The associations of SOESPEN, SOESPEN-M, and their components with falls were analyzed.
RESULTS: Among the 1353 participants, the prevalence of SO was 13.2 % (SOESPEN) and 11.4 % (SOESPEN-M), which increased with age and higher BMI levels. Within participants with a normal BMI, 4.2 % and 6.2 % were found to have SOESPEN and SOESPEN-M, respectively. SMM/W and SMM/BMI negatively correlated with fall risk (p=0.042 and p=0.021, respectively). Upon adjusting for confounders, only SOESPEN was significantly associated with falls (odds ratios [OR] 1.61, 95 % confidence interval [CI] 1.08 to 2.40), whereas the association for SOESPEN-M did not achieve significance (OR 1.55, 95 % CI 0.99 to 2.43).
CONCLUSIONS: This research validated the ESPEN/EASO criteria (SOESPEN) and their modified version (SOESPEN-M) among community-dwelling older adults in Western China. The SMM/BMI adjustment appears to offer a lower estimate of SO prevalence, with only SOESPEN showing a significant association with falls.

BACKGROUND: Ventilator-associated pneumonia (VAP) is a prevalent and grave hospital-acquired infection that affects mechanically ventilated patients. Diverse diagnostic criteria can significantly affect VAP research by complicating the identification and management of the condition, which may also impact clinical management.
OBJECTIVE: We conducted this review to assess the diagnostic criteria and the definitions of the term \"ventilator-associated\" used in randomised controlled trials (RCTs) of VAP management.
METHODS: Based on the protocol (PROSPERO 2019 CRD42019147411), we conducted a systematic search on MEDLINE/PubMed and Cochrane CENTRAL for RCTs, published or registered between 2010 and 2024.
METHODS: We included completed and ongoing RCTs that assessed pharmacological or non-pharmacological interventions in adults with VAP.
METHODS: Data were collected using a tested extraction sheet, as endorsed by the Cochrane Collaboration. After cross-checking, data were summarised in a narrative and tabular form.
RESULTS: In total, 7,173 records were identified through the literature search. Following the exclusion of records that did not meet the eligibility criteria, 119 studies were included. Diagnostic criteria were provided in 51.2% of studies, and the term \"ventilator-associated\" was defined in 52.1% of studies. The most frequently included diagnostic criteria were pulmonary infiltrates (96.7%), fever (86.9%), hypothermia (49.1%), sputum (70.5%), and hypoxia (32.8%). The different criteria were used in 38 combinations across studies. The term \"ventilator-associated\" was defined in nine different ways.
CONCLUSIONS: When provided, diagnostic criteria and definitions of VAP in RCTs display notable variability. Continuous efforts to harmonise VAP diagnostic criteria in future clinical trials are crucial to improve quality of care, enable accurate epidemiological assessments, and guide effective antimicrobial stewardship.

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OBJECTIVE: As a large and populous country, China releases a high number of diagnostic criteria. However, the published diagnostic criteria have not yet been systematically analyzed. Therefore, the aim of this study is to investigate the characteristics, development methods, reporting quality, and evidence basis of diagnostic criteria published in China.
METHODS: We searched five databases for diagnostic criteria from their inception until July 31, 2023. All diagnostic criteria were screened through abstract and full-text reading, and included if satisfying the prespecified criteria. Two researchers independently extracted data on the characteristics, development methods, reporting quality, and evidence basis of diagnostic criteria.
RESULTS: A total of 143 diagnostic criteria were included. In terms of development methods, the proportions of diagnostic criteria that involved a systematic literature search (n = 2; 1.4%; 95% confidence interval (CI), 0.4% to 5.0%), adoption of formal consensus methods (n = 4; 2.8%; 95% CI, 1.1% to 7.0%), and criteria validation (n = 9; 6.3%; 95% CI, 3.3% to 11.5%) were relatively low. Regarding reporting quality, the average compliance with the ACCORD checklist was 5.1%; none of the diagnostic criteria reported on registration, expert inclusion criteria, expert recruitment process, or consensus results. A majority (58.7%; 95% CI, 50.6% to 66.5%) of criteria did not cite any research, and only one (0.7%; 95% CI, 0.1% to 3.9%) criterion was derived from a systematic review. Moreover, only 16.1% (95% CI, 11.0% to 23.0%) of diagnostic criteria used evidence from the Chinese population.
CONCLUSIONS: The diagnostic criteria developed in China exhibit serious flaws, particularly in evidence retrieval, formation of expert panels, consensus methods, and validation. Additionally, only few diagnostic criteria used a systematic synthesis of the evidence or evidence from the China. There is an urgent need to enhance the methodology for developing diagnostic criteria.

The diagnostic workup of multiple sclerosis (MS) has evolved considerably. The 2017 revision of the McDonald criteria shows high sensitivity and accuracy in predicting clinically definite MS in patients with a typical clinically isolated syndrome and allows an earlier MS diagnosis. Neuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein-immunoglobulin G-associated disease (MOGAD) are recognized as separate conditions from MS, with specific diagnostic criteria. New MR imaging markers may improve diagnostic specificity for these conditions, thus reducing the risk of misdiagnosis. This study summarizes the most recent updates regarding the application of MR imaging for the diagnosis of MS, NMOSD, and MOGAD.

BACKGROUND: Information on infective endocarditis (IE) caused by Cutibacterium spp. is limited and new Duke-ISCVID criteria have not yet been properly assessed. We examined clinical characteristics, outcomes and performance of diagnostic tests for Cutibacterium valvular and cardiac implantable electronic device-related IE (CIED-IE).
METHODS: Data corresponding to all episodes of Cutibacterium IE recorded from 2008 to 2023 in a prospective national cohort including 46 Spanish hospitals were examined. Possible IE cases were reassessed using the new criteria. The sensitivity of blood cultures, valvular and CIED cultures, and PCR of the 16SrRNA gene and sequencing (16SPCR) was evaluated.
RESULTS: There were 67/6,692 (1%) episodes of IE caused by Cutibacterium spp., 85% affecting men. Of these, 50 were valve-related (45 prosthetic, 5 native) and 17 CIED-related. The new criteria identified 8 additional cases and reclassified 15 as definite IE. Intracardiac complications (abscess, pseudoaneurysm, perforation or intracardiac fistula) occurred in 23/50 (46%) valvular IE episodes, leading to 18% mortality, and up to 40% mortality if surgery was indicated but could not be performed. All CIED-IE cases underwent device removal and no deaths were recorded. Positive diagnosis rates for blood cultures, valve/device cultures and 16SPCR were 52%, 70% and 82%, respectively.
CONCLUSIONS: Cutibacterium IE is a rare yet potentially life-threatening condition that warrants a high index of suspicion in men with endovascular prosthetic material. The new Duke-ISCVID criteria and molecular techniques are useful for its diagnosis. Considering a significant complication rate, cardiac surgery and removal of CIEDs play a key role in reducing mortality.