Summary
Background
High‐mobility group box 1 (HMGB1) is a damage‐associated molecular‐pattern protein. Stevens–Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) are serious, immune‐mediated ...skin‐blistering conditions.
Objectives
To determine serum and/or blister‐fluid total HMGB1 levels in SJS/TEN cohorts, and HMGB1 expression in formalin‐fixed, paraffin‐embedded (FFPE) SJS/TEN skin vs. healthy and maculopapular exanthema (MPE) skin.
Methods Serum HMGB1 was quantified in Malawian nevirapine‐induced hypersensitivity, Taiwanese SJS/TEN and Spanish SJS/TEN cohorts. FFPE skin (healthy skin, MPE, SJS/TEN) was stained and assessed for HMGB1 expression.
Results
Serum total HMGB1 was not significantly elevated in patients with nevirapine‐induced SJS/TEN (3·98 ± 2·17 ng mL−1), MPE (3·92 ± 2·75 ng mL−1) or drug reaction with eosinophilia and systemic symptoms (4·73 ± 3·00 ng mL−1) vs. tolerant controls (2·97 ± 3·00 ng mL−1). HMGB1 was significantly elevated in Taiwanese patients with SJS/TEN, highest during the acute phase (32·6 ± 26·6 ng mL−1) vs. the maximal (19·7 ± 23·2 ng mL−1; P = 0·007) and recovery (24·6 ± 25·3 ng mL−1; P = 0·027) phases. In blister fluid from Spanish patients with SJS/TEN, HMGB1 (486·8 ± 687·9 ng mL−1) was significantly higher than in serum (8·8 ± 7·6 ng mL−1; P <0·001). Preblistered SJS/TEN skin showed decreased epidermal nuclear HMGB1 expression in upper epidermis vs. healthy or MPE skin but retained basal/suprabasal expression.
Conclusions
Epidermal HMGB1 expression was decreased in SJS/TEN skin. Retained basal/suprabasal epidermal HMGB1 expression may exacerbate localized injury in SJS/TEN.
What's already known about this topic?
High‐mobility group box 1 (HMGB1) is a marker of tissue injury and innate immune response.
Elevation of serum HMGB1 in patients with serious cutaneous adverse drug reactions has been reported previously.
To date, no analysis of HMGBI distribution in Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) patient blister‐fluid and skin biopsy tissue has been described.
What does this study add?
This study confirms serum HMGB1 elevation in SJS/TEN in three independent cohorts.
It reports, for the first time, super‐elevation of HMGB1 in blister fluid and significantly decreased epidermal expression in preblistered SJS/TEN skin with suprabasal retention.
These results are highly distinct from healthy or maculopapular exanthema skin and may represent a viable diagnostic tool.
Linked Comment: Dodiuk‐Gad. Br J Dermatol 2019; 181:18–19.
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Pain is a subjective and multidimensional experience that is often inadequately managed in clinical practice. Effective control of postoperative pain is important after anesthesia and surgery. A ...systematic review was conducted to identify the independent predictive factors for postoperative pain and analgesic consumption. The authors identified 48 eligible studies with 23,037 patients included in the final analysis. Preoperative pain, anxiety, age, and type of surgery were four significant predictors for postoperative pain. Type of surgery, age, and psychological distress were the significant predictors for analgesic consumption. Gender was not found to be a consistent predictor as traditionally believed. Early identification of the predictors in patients at risk of postoperative pain will allow more effective intervention and better management. The coefficient of determination of the predictive models was less than 54%. More vigorous studies with robust statistics and validated designs are needed to investigate this field of interest.
Background: An ultrasound-guided erector spinae plane block (ESPB) has emerged as an effective way to control postoperative pain and may be a good alternative way to an epidural block. However, ...relevant research on the appropriate concentration of local anesthetics for an ESPB remains scarce. Aims: This study aimed to investigate the optimal concentration of ropivacaine for an ESPB in patients undergoing video-assisted thoracoscopic surgery (VATS). Methods: A total of 68 patients who underwent a VATS lobectomy were enrolled. An ipsilateral ultrasound-guided ESPB was performed with three different ropivacaine concentrations as a local anesthetic: 0.189% (G1), 0.375% (G2), and 0.556% (G3). The total amount of perioperative remifentanil administered, patient-controlled analgesia (PCA) applied, and rescue drugs for postoperative analgesia during the 24 h after surgery were acquired, and numeric rating scale (NRS) scores were obtained. Results: The total amount of intraoperative remifentanil administered was 7.20 ± 3.04 mcg/kg, 5.32 ± 2.70 mcg/kg, and 4.60 ± 1.75 in the G1, G2, and G3 groups, respectively. G2 and G3 had significantly lower amounts of remifentanil administered than the G1 group (P = 0.02 vs. G2; P = 0.003 vs. G3). The G3 group needed more inotropes than the G1 and G2 groups in the perioperative period (P = 0.045). The NRS scores, PCA, and rescue drug were not significantly different in the three groups. Conclusion: The optimal concentration of ropivacaine recommended for an ESPB was 0.375%, which was effective in controlling pain and reducing the intraoperative opioid requirements with minimal adverse reactions such as hypotension.
To evaluate patient outcome and investigate the prognostic factors of high-grade meningiomas by adopting the 2000 World Health Organization (WHO) classification system.
Between 1986 and 2004, 74 ...patients were diagnosed with high-grade meningioma: 33 with atypical and 41 with anaplastic meningioma. The mean follow-up was 58.5 months. We reclassified all surgical specimens, according to the 2000 WHO classification system, using two expert neuropathologists.
Forty of 74 meningiomas were reclassified as atypical meningioma and 24 as anaplastic meningioma. Overall and recurrence-free survivals were significantly longer in patients with atypical than in those with anaplastic meningioma: 142.5 versus 39.8 months and 138.5 versus 32.2 months, respectively (p<0.001). In patients with atypical meningiomas, brain invasion and adjuvant radiotherapy were not associated with survival; however, in the brain invasion subgroup, adjuvant radiotherapy improved patients' survival. In patients with anaplastic meningioma, the prognostic factors were brain invasion, adjuvant radiotherapy, malignant progression, p53 overexpression and extent of resection. The p53 overexpression was the only factor associated with malignant progression (p = 0.009).
The 2000 WHO classification has identified the truly aggressive meningiomas better than did the previous criteria. A precise meningioma grading system may help to avoid over-treatment of patients with an atypical meningioma as, once the tumour has "declared itself" by recurrence and histological features, it becomes a tumour that is poorly amenable to current therapies.
Different clones, protocol conditions, instruments, and scoring/readout methods may pose challenges in introducing different PD-L1 assays for immunotherapy. The diagnostic accuracy of using different ...PD-L1 assays interchangeably for various purposes is unknown. The primary objective of this meta-analysis was to address PD-L1 assay interchangeability based on assay diagnostic accuracy for established clinical uses/purposes. A systematic search of the MEDLINE database using PubMed platform was conducted using "PD-L1" as a search term for 01/01/2015 to 31/08/2018, with limitations "English" and "human". 2,515 abstracts were reviewed to select for original contributions only. 57 studies on comparison of two or more PD-L1 assays were fully reviewed. 22 publications were selected for meta-analysis. Additional data were requested from authors of 20/22 studies in order to enable the meta-analysis. Modified GRADE and QUADAS-2 criteria were used for grading published evidence and designing data abstraction templates for extraction by reviewers. PRISMA was used to guide reporting of systematic review and meta-analysis and STARD 2015 for reporting diagnostic accuracy study. CLSI EP12-A2 was used to guide test comparisons. Data were pooled using random-effects model. The main outcome measure was diagnostic accuracy of various PD-L1 assays. The 22 included studies provided 376 2×2 contingency tables for analyses. Results of our study suggest that, when the testing laboratory is not able to use an Food and Drug Administration-approved companion diagnostic(s) for PD-L1 assessment for its specific clinical purpose(s), it is better to develop a properly validated laboratory developed test for the same purpose(s) as the original PD-L1 Food and Drug Administration-approved immunohistochemistry companion diagnostic, than to replace the original PD-L1 Food and Drug Administration-approved immunohistochemistry companion diagnostic with a another PD-L1 Food and Drug Administration-approved companion diagnostic that was developed for a different purpose.
Abstract Background Laparoscopic resection of gastric gastrointestinal stromal tumors (GISTs) has been shown by several retrospective studies to be technically feasible and associated with favorable ...outcomes when compared to the open approach. This study aims to mitigate potential selection bias by performing a case control study of laparoscopic (LWR) versus open wedge resection (OWR) matched by resection type, location and tumor size. Methods We retrospectively identified 50 consecutive patients who underwent LWR for a suspected gastric GIST from a prospective database and matched this cohort with 50 patients who underwent OWR. Results There was no statistical difference between the key baseline clinicopathological features of patients' who underwent LWR versus OWR. Patients who underwent LWR had longer operating times 150 (range, 65–270) minutes vs 92.5 (25–200) minutes, P < .001 but decreased median blood loss 0 (0–300) ml vs 0 (0–1200) ml, P = .015, decreased frequency of intraoperative or postoperative blood transfusion 1 (2%) vs 8 (16%), P = .031, decreased median time to liquid diet 2 (0–5) vs 3 (1–7) days, P < .001, decreased median time to solid diet 3 (1–6) vs 5 (2–11) days, P < .001 and decreased postoperative stay 4 (2–10) vs 4.5 (3–17), P < .001 compared to OWR. There was no difference in oncological outcomes such as frequency of close margins (≤1 mm) and recurrence-free survival. Conclusion This matched case–control study provides supporting evidence that LWR results in superior perioperative outcomes compared to OWR without compromising on oncological outcomes.
Triaging and prioritising patients for RT-PCR test had been essential in the management of COVID-19 in resource-scarce countries. In this study, we applied machine learning (ML) to the task of ...detection of SARS-CoV-2 infection using basic laboratory markers. We performed the statistical analysis and trained an ML model on a retrospective cohort of 5148 patients from 24 hospitals in Hong Kong to classify COVID-19 and other aetiology of pneumonia. We validated the model on three temporal validation sets from different waves of infection in Hong Kong. For predicting SARS-CoV-2 infection, the ML model achieved high AUCs and specificity but low sensitivity in all three validation sets (AUC: 89.9-95.8%; Sensitivity: 55.5-77.8%; Specificity: 91.5-98.3%). When used in adjunction with radiologist interpretations of chest radiographs, the sensitivity was over 90% while keeping moderate specificity. Our study showed that machine learning model based on readily available laboratory markers could achieve high accuracy in predicting SARS-CoV-2 infection.
Cutaneous idiosyncratic drug reactions (CIDRs) are usually unpredictable, ranging from mild maculopapular exanthema (MPE) to severe cutaneous adverse drug reactions (SCARs) such as drug reaction with ...eosinophilia and systemic symptoms (DRESS), Stevens‐Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). Increasing evidence suggests that HLA alleles are strongly associated with drug‐induced‐CIDRs. The pathomechanisms for CIDRs include genetic polymorphisms affecting complex immune‐specific HLA/drug antigen/T‐cell receptor interactions and drug metabolism. Pharmacogenomic tests to prevent CIDRs have been widely implemented in clinical practice in recent years.
Early detection of local recurrence is important to increase the chance of cure because local recurrence is the main cause of treatment failure in head and neck squamous cell carcinoma. We evaluated ...the added value of voxel-based color maps of dynamic contrast-enhanced MR imaging compared with conventional MR imaging alone for detecting local recurrence of head and neck squamous cell carcinoma.
We retrospectively enrolled 63 consecutive patients with head and neck squamous cell carcinoma after definitive treatment and posttreatment surveillance MR imaging studies that demonstrated focal enhancement at the primary site. Three independent readers assessed conventional MR imaging and a pair of color maps of initial and final 90-second time-signal intensity areas under the curve from dynamic contrast-enhanced MR imaging. The sensitivities, specificities, and accuracies of both conventional MR imaging alone and combined interpretation of conventional and dynamic contrast-enhanced MR imaging were assessed using the clinicopathologic diagnosis as the criterion standard. κ statistics were used to evaluate interreader agreement.
There were 28 patients with subsequently documented local recurrence and 35 with posttreatment change. Adding dynamic contrast-enhanced MR imaging to conventional MR imaging significantly increased the diagnostic accuracies for detecting local recurrence (48%-54% versus 87%-91%;
< .05), with excellent interreader agreement (κ = 0.8; 95% CI, 0.67-0.92 to κ = 0.81; 95% CI, 0.69-0.93). By all 3 readers, the specificities were also significantly improved by adding dynamic contrast-enhanced MR imaging to conventional MR imaging (22%-43% versus 87%-91%;
< .001) without sacrificing the sensitivities (68%-82% versus 86%-89%;
> .05).
Adding voxel-based color maps of initial and final 90-second time-signal intensity areas under the curve from dynamic contrast-enhanced MR imaging to conventional MR imaging increases the diagnostic accuracy to detect local recurrence in head and neck squamous cell carcinoma by improving the specificity without sacrificing the sensitivity.
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