Agostino Gemelli University Polyclinic

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Direct immunofluorescence (DIF) is the gold standard for diagnosing subepidermal blistering diseases (SBDs). However, DIF requires specialized expertise; therefore, alternative immunological methods such as enzyme-linked immunosorbent assays (ELISA) are worth exploring. The aim of this review was to evaluate the diagnostic agreement between DIF and ELISA for the diagnosis of SBD. A systematic literature review of international journals and electronic databases (MEDLINE via OVID, Scopus, and Web of Science) was conducted between their inception and December 2023. The risk of bias and overall quality of evidence were assessed using the Newcastle-Ottawa Scale and the GRADE system. Of the 1691 articles identified, 38 were included in the qualitative synthesis and 37 in the quantitative analysis. Three meta-analyses were developed and revealed the superiority of DIF over ELISA, with the following risk differences: BP180, 0.26 (95% CI: 0.19-0.33, p < 0.00001, I 2 : 96%); BP230, 0.59 (95% CI: 0.47-0.71, p < 0.00001, I 2 : 98%); and Lam332, 0.82 (95% CI: 0.70-0.94, p < 0.00001, I 2 : 89%). DIF remains the gold standard for the diagnosis of autoimmune SBDs. ELISA can serve as a complementary diagnostic tool, especially as a follow-up instrument for patients with SBD, owing to its low invasiveness.

Polyhydramnios is usually diagnosed with an amniotic fluid index (AFI) ≥ 24.0 cm or a maximum vertical pocket (MVP) ≥ 8.0 cm [1]. However, which methodology—AFI versus MVP—has a stronger association with adverse perinatal outcomes is uncertain. Our aim was to undertake a systematic review of the literature of studies comparing AFI, MVP or AFI&MVP for polyhydramnios related to adverse perinatal outcomes. We conducted a systematic review of the literature. Medline, Cochrane Library, EMBASE, Pubmed Central, Scopus and ClinicalTrial.gov were electronically searched from their inception to April 2025. Multiple combinations of (MeSH) terms and word variants (‘amniotic fluid index’, ‘AFI’, ‘deepest vertical pocket’, ‘DVP’, ‘maximum vertical pocket’, ‘MVP’, ‘polyhydramnios’, ‘hydramnios’) were used. No restrictions for geographic location or temporal limit were applied. Evaluation of each included study followed the Newcastle Ottawa Scale for cohort studies [2]. Disagreements were resolved by discussion until a consensus was reached. As we originally planned to do a systematic review and meta-analysis, the review was registered with the PROSPERO International Prospective Register of Systematic Reviews (registration No. CRD420251040958). Studies were included if they evaluated adverse perinatal outcomes by either AFI, MVP or AFI and MVP for the diagnosis of polyhydramnios. Electronic search, inclusion criteria and risk of bias assessment were independently assessed by two reviewers (AP and VB). Data from each eligible study were extracted without modification of original data onto custom-made data collection forms. The primary outcome was perinatal mortality, as defined by the included studies [3] (sum of stillbirths and neonatal deaths). Secondary outcomes were large for gestational age (LGA) or macrosomia (estimate of fetal weight ≥ 90th percentile or absolute weight ≥ 4000 g, respectively), fetal growth restriction (FGR, estimate of fetal weight < 10th percentile or as defined by included studies), IUFD, neonatal intensive care unit (NICU) admission and neonatal death. Out of 133 studies screened, there were no RCTs comparing the outcomes using MVP, AFI or both. Five non-RCT studies were assessed for eligibility for a total of 5319 patients [3-7] (Figure 1). However, only one retrospective study reported neonatal outcomes [7] (Table 1) and could be included in the analysis, and it was judged as low quality. In this study, polyhydramnios was identified by an AFI ≥ 24 cm or an MVP ≥ 8 cm on at least one ultrasound ≥ 20 weeks [7]. Those diagnosed with polyhydramnios by both methods had an increased risk of perinatal mortality (aRR = 5.94, 95% CI 3.07–11.50), including IUFD (aRR = 5.58, 95% CI 2.81–11.09) and neonatal death (aRR = 13.07, 95% CI 1.72–99.60), compared to those with normal amniotic fluid (Table 1). Only MVP and AFI were associated with increased risks of FGR, IUFD, NICU admission, neonatal and perinatal death (Table 1). Although polyhydramnios is frequently found in clinical practice, there is limited prospective, high-quality data concerning the best ultrasonographic methodology associated with adverse perinatal outcomes. Only Kraus et al. [7] compare AFI, MVP or both in terms of adverse perinatal outcomes, finding that polyhydramnios diagnosed by both methods is associated with an increased risk of perinatal mortality (Table 1). This is interestingly in contrast with the literature regarding oligohydramnios. A recent meta-analysis included 6 RCTs for a total of 4278 patients in the setting of oligohydramnios [4] showed that the use of MVP was associated with significantly lower rates of non-reassuring fetal heart tracing, Caesarean Delivery for non-reassuring fetal heart testing, and induction of labour, but without any worsening of adverse pregnancy outcomes [4]. To our knowledge, there are no ongoing RCTs on polyhydramnios diagnosis in terms of adverse perinatal outcomes. There is an urgent need for RCTs comparing different ultrasonographic methodologies for the diagnosis of polyhydramnios in terms of adverse perinatal outcomes, leading to an evidence-based management of polyhydramnios in everyday clinical practice. All authors fulfil the criteria of authorship. The authors have nothing to report. Transparency: The lead author (the manuscript's guarantor) affirms that the manuscript is an honest, accurate and transparent account of the study being reported; that no important aspects of the study have been omitted and that any discrepancies from the study as planned have been explained. The authors have nothing to report. The authors have nothing to report. The authors declare no conflicts of interest. The data that support the findings of this study are available from the corresponding author upon reasonable request.

Seasonal changes, particularly increased daylight exposure, are known to influence dopamine transporter (DAT) availability, potentially affecting mood disorders such as major depressive disorder (MDD). This study aimed to evaluate seasonal variations in the striatum using ¹²³I-FP-CIT SPECT in patients with MDD, and examine associations with specific psychopathological symptoms. In this retrospective study, DAT SPECT scans from 85 patients with MDD were analyzed according to the season of imaging-fall-winter (FW) or spring-summer (SS). Psychometric assessments included the Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Rating Scale (HAMA), Snaith-Hamilton Pleasure Scale (SHAPS), and Depression Retardation Rating Scale (DRRS). No overall differences in DAT availability were observed between FW and SS. However, anhedonia levels were higher in FW (p = 0.050). Patients with severe depression (HAMD ≥ 25) showed lower DAT availability in the left putamen, especially during SS (p = 0.014). Patients with marked psychomotor retardation (DRRS ≥ 18) exhibited reduced DAT availability in the left putamen (p = 0.002), with further reductions across all striatal regions during SS. Patients with suicidal ideation showed decreased DAT in the right (p = 0.029) and left putamen (p = 0.015). A negative correlation was found between DRRS scores and left putamen DAT availability (p = 0.034). Reduced DAT availability is associated with key depressive symptoms, notably psychomotor retardation and suicidal ideation. Seasonal effects, especially in the SS period, may exacerbate dopaminergic dysregulation. These findings support integrating seasonal and neurobiological factors in the assessment and management of severe MDD.