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Predictive Histopathological Markers for Upstaging to Invasive Carcinoma after a Biopsy Diagnosis of Ductal Carcinoma in situ of the Breast:A Hypothesis-Generating Systematic Review
No full textIntroduction: Around 25% of patients with a biopsy diagnosis of pure ductal carcinoma in situ (DCIS) will be upstaged to invasive breast carcinoma (IBC) after surgery. Because of this upstaging risk, patients with high grade DCIS frequently undergo a sentinel lymph node procedure (SLNP), which can cause surgery-induced morbidity. Presentation with a palpable mass increases the upstaging risk, but histopathological predictors are currently unclear. This PROSPERO-registered systematic review aims to identify which biopsy-based histopathological markers can predict the presence of IBC in the subsequent resection. These results might help to reserve SLNPs for selected high-risk patients, aiming to personalize treatment. Methods: PubMed, Embase, and Scopus were searched for content using predefined search queries. Three reviewers independently screened the literature in Rayyan by applying predefined criteria and retained 36 reports. Studies including DCIS with micro-invasion were excluded. Results: This systematic review comprised 18, 475 patients. The median cohort size was 267 patients (range: 67–3, 780). Most studies were retrospective (33/36). The median upstaging risk was 26% (range: 8–52%). The reports studied twenty-three histopathological and immunohistochemical features. Only seven features were investigated in multiple studies, all yielding contradictory results. For instance, thirty-three studies investigated nuclear grade, but only 18 reports demonstrated a significant association with upstaging, independent from cohort size.Conclusion: No robust histopathological features can be recommended at present to reliably predict the upstaging risk to IBC after a biopsy diagnosis of pure DCIS. We discuss several hypotheses, aiming to explain these contradictory data. Ideally, large-scale multicentre prospective studies should be organized to answer this unmet clinical need.</p
Harms of Antenatal Corticosteroids Among Infants Born at Term:Cause for Concern or Caused by Bias?
No full textGuided growth for the correction of angular lower limb deformity:Correction rates for idiopathic and non-idiopathic aetiologies
No full textINTRODUCTION: Coronal plane knee deformities are frequent in children and may arise from idiopathic or nonidiopathic causes, leading to cosmetic, functional, or early degenerative issues. Guided growth using tension band plates is an established corrective method, but its predictability - especially in nonidiopathic cases - needs further evaluation. This study analyzed correction rates (CR) and treatment outcomes in different etiologies.METHODS: A retrospective review included patients treated for coronal plane deformities with tension band plates from 2009 to 2021. Patients were classified according to etiology. Radiographic measurements (mechanical axis deviation, mLDFA, and mMPTA) were compared between baseline and end of correction. Analyses regarding treatment success, CR and predictors for CR and success were performed.RESULTS: The analysis included 654 growth modulations in 313 children; distal femur (55.4%), proximal tibia (44.6%), both (42.2%. The average CR for mLDFA was 0.67 (+/-0.55)°/month and for mMPTA 0.43 (+/-0.38)°/month. CR significantly varied by etiology ( p < 0.001), with older age at surgery and varus deformity predicting lower CRs. Neutral mechanical axis was achieved in 68.7% of patients. Significant differences between etiologies were seen, and complete correction was achieved significantly more often in patients with idiopathic etiology compared to nonidiopathic etiologies; 78.2% vs. 66.3% respectively, p = 0.02. CONCLUSION: Hemi-epiphysiodesis is effective for correcting coronal plane deformities in children, but CR differs by etiology and incomplete correction is not uncommon. These factors should inform treatment planning and follow-up.LEVEL OF EVIDENCE: Level IV, case-series.</p
Intrahepatic Cholangiocarcinoma:Recurrence Patterns, Genomics, and Survival
No full textPURPOSE:– The impact of first recurrence site on outcome after resection of intrahepatic cholangiocarcinoma (IHC) is ill-defined, as are the genomic underpinnings of recurrence and outcomes. METHODS:– Resected patients with IHC at two institutions with genomic data were included. Sites of first recurrence (SOFR) were classified as liver only (LO), extrahepatic (EH) only, or simultaneous liver and extrahepatic (SIM). Overall survival (OS) was calculated from the time of recurrence. RESULTS: – Between 1993 and 2021, 318 patients met inclusion criteria; 232 (73%) recurred. SOFR were LO = 93 (40%), EH = 80 (34%), and SIM = 59 (26%). Median OS from recurrence was similar in the LO (33 [26, 42] months) and EH groups (33 [23, 46] months) but much lower in SIM (12 [9.8, 18] months; P <.001). Moderate/poor tumor differentiation, lymphovascular invasion, N1 disease, perineural invasion, and time to recurrence (all P <.05) were associated with SIM; only positive resection margin predicted LO (P =.007). No individual genomic or pathway alterations predicted SOFR; however, for all recurrers, TP53mut (n = 51, 22%; hazard ratio [HR], 2.0 [1.4 to 2.9]; P =.002), CDKN2Adel (n = 34, 15%; HR, 3.4 [95% CI, 2.2 to 5.3]; P <.001), CDKN2B (n = 25, 11%; HR, 3.2 [95% CI, 2.0 to 5.0]; P <.001), and KRASmut (n = 25, 11%; HR, 2.5 [95% CI, 1.6 to 4.0]; P =.002) were associated with worse OS. On multivariable analysis, SIM (HR, 2.5 [95% CI, 1.7 to 3.5]; P <.001), N1 status (HR, 1.8 [95% CI, 1.2 to 2.6]; P =.004), and alterations in the high-risk genotype (TP53mut, CDKN2Adel or KRASmut; n = 84, 36%; HR, 2.4 [95% CI, 1.7 to 3.3]; P <.001) were independent predictors of poor OS. CONCLUSION:– Recurrence after resection of IHC is common, and the liver was the most common site (66%). Clinicopathologic and genomic factors had limited ability to predict SOFR. Although LO and EH were associated with similar OS, SIM recurrences had dramatically worse OS. Adjuvant strategies targeting liver recurrence may improve outcomes after resection of IHC.</p
Translating Q methodology results into survey questions for large-scale use:a comparison of approaches
No full textDeveloping Q to survey (Q2S) approaches from underlying Q methodology studies offers huge potential to design quantitative surveys in a systematic, transparent way for any topic. However, Q2S is underdeveloped despite calls for more methodological testing. This paper is the first to compare the performance of four different Q2S approaches in terms of their feasibility, validity and reliability. The four Q2S approaches were: rating statements; ranking blocks of statements; mini-Q; and rating short narratives. Encouragingly, we find that all four Q2S approaches seem to perform well, meaning flexibility is retained in how Q2S studies are designed. Further testing of these approaches and alternative ones is required. Avenues for further research, and characteristics of the underlying Q study and purpose of the Q2S study that may influence the choice of Q2S approach are discussed.</p
Bridging in Left Ventricular Assist Device Outpatients:Exposure Misclassification and Heterogeneous Bleeding Risk
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Anti-N-methyl-D-aspartate receptor encephalitis:insights and future treatment directions
No full textTwo decades after the first recognition of anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis, advances have led to consensus-based diagnostic criteria and treatment recommendations, yet no FDA-approved therapies exist. Recent studies highlight limitations of serum-only antibody testing, importance of tailored tumor surveillance, and epidemiologic variation across racial and ethnic groups. Prognostic indicators, exemplified by the anti-NMDAR encephalitis 1-year functional status (NEOS) score, have refined outcome prediction. Although nearly 80% of patients achieve favorable functional outcomes, persistent neuropsychiatric and cognitive deficits may impact quality of life, highlighting the need for improved therapeutic strategies. Accordingly, randomized clinical trials are underway, including studies evaluating B cell- and interleukin-6 (IL-6)-targeted therapies, for anti-NMDAR encephalitis. This review synthesizes these developments and discusses current treatment approaches with a focus on emerging investigational therapies.</p