Outcome-Based Risk Stratification Model for the Diagnosis of Placental Maternal Vascular Malperfusion.

The Amsterdam Consensus Statement introduced the term maternal vascular malperfusion (MVM) to group a constellation of findings associated with impaired maternal-placental circulation. In isolation, these findings are relatively common in placentas from normal gestations, and there is uncertainty on how many, and which, are required. We aimed to determine the criteria essential for MVM diagnosis in correlation with obstetrical outcomes. A total of 200 placentas (100 with a reported diagnosis of MVM and 100 controls matched by maternal age and gravida-para-abortus status) were reviewed to document MVM features. Obstetrical outcomes in the current pregnancy were recorded including hypertension, pre-eclampsia with or without severe features, gestational diabetes, prematurity, fetal growth restriction, and intrauterine fetal demise. On univariate logistic regression analysis, adverse outcome was associated with low placental weight (LPW, <10% percentile for gestational age), accelerated villous maturation (AVM), decidual arteriopathy (DA), infarcts (presence and volume), distal villous hypoplasia, and excess multinucleated trophoblast in basal plate ≥2 mm (all P < .01) but not with retroplacental hemorrhage. In a multivariable model DA, infarcts and AVM were significantly associated with adverse outcomes, whereas LPW showed a trend toward significance. A receiver-operating characteristic curve including these 4 parameters showed good predictive ability (area under the curve [AUC], 0.8256). Based on the probability of an adverse outcome, we recommend consistent reporting of DA, AVM, infarcts, and LPW, summarizing them as "diagnostic of MVM" (DA or AVM plus any other feature, yielding a probability of 65%-97% for adverse obstetrical outcomes) or "suggestive of MVM" (if only 1 feature is present, or only 2 features are infarcts plus LPW, yielding a probability of up to 52%). Other features such as distal villous hypoplasia, excess (≥2 mm) multinucleated trophoblast, and retroplacental hemorrhage can also be reported, and their role in MVM diagnosis should be further studied.

Atypical Droplet Digital Polymerase Chain Reaction Patterns That Indicate Uncommon but Clinically Actionable EGFR Mutations in Lung Cancer.

CONTEXT.­: Droplet digital polymerase chain reaction (ddPCR) is a sensitive method to detect common pathogenic EGFR mutations in non-small cell lung cancer. Although targeted assays have not been specifically designed to detect them, uncommon EGFR mutations have been linked to response to targeted therapy. OBJECTIVE.­: To describe atypical ddPCR patterns that correspond to uncommon but clinically actionable EGFR mutations. DESIGN.­: A cohort of 1134 consecutive non-small cell lung cancers that underwent targeted next-generation sequencing was reviewed. Uncommon EGFR mutations involving probe binding sites were evaluated by ddPCR. RESULTS.­: Two hundred fifty-five of 1134 cancers (22.5%) harbored pathogenic EGFR mutations. One hundred eighty-six of 255 (72.9%) had canonical EGFR exon 19 deletion or exon 21 p.L858R variants designed for detection by ddPCR. An additional 25 of 255 cases (9.8%) had uncommon EGFR mutations within the probe-binding site, including one case with concurrent uncommon mutations in both exon 19 and exon 21. These mutations included uncommon EGFR exon 19 deletions (n = 6), EGFR exon 19 substitutions p.L747P (n = 3) and p.L747A (n = 1), dinucleotide substitutions leading to EGFR p.L858R (n = 5), EGFR exon 21 substitutions p.K860I (n = 1) and p.L861Q (n = 9), and EGFR p.[L858R;K860I] (n = 1). Droplet digital polymerase chain reaction generated atypical but reproducible signal for each of these uncommon variants. CONCLUSIONS.­: Droplet digital polymerase chain reaction analysis of uncommon pathogenic EGFR variants can yield unique and reproducible results. Recognition of atypical patterns in EGFR ddPCR testing can prompt confirmatory molecular testing and aid appropriate targeted therapy selection for patients with non-small cell lung cancer.

Placental lesions attributed to shallow implantation, excess extravillous trophoblast and decidual hypoxia: Correlation with maternal vascular malperfusion and related obstetric conditions.

INTRODUCTION: Maternal vascular malperfusion (MVM) is one of four main patterns of placental injury defined by the Amsterdam consensus statement and is associated with adverse fetal and maternal outcomes. Laminar decidual necrosis (DLN), extravillous trophoblast islands (ETIs), placental septa (PS), and basal plate multinucleate implantation-type trophoblasts (MNTs) are lesions attributed to decidual hypoxia, excess trophoblast, and shallow implantation, but are not included in the current MVM diagnostic criteria. We aimed to investigate the relationship between these lesions and MVM. METHODS: A case-control model was used to evaluate for DLN, ETIs, PS, and MNTs. Placentas with MVM on pathologic examination (defined as ≥2 related lesions) constituted the case group, and maternal age- and GPA-status-matched placentas with less than 2 lesions constituted the control group. MVM-related obstetric morbidities were recorded, including hypertension, preeclampsia, and diabetes. These were correlated with the lesions of interest. RESULTS: 200 placentas were reviewed: 100 MVM cases and 100 controls. MNTs and PS showed significant enrichment in the MVM group (p < .05). Furthermore, larger foci of MNTs (>2 mm linear extent) were significantly associated with chronic or gestational hypertension (OR = 4.10; p < .05) and preeclampsia (OR = 8.14; p < .05). DLN extent correlated with placental infarction, but DLN and ETIs (including size and number) lacked association with MVM-related clinical conditions. DISCUSSION: As a marker of abnormally shallow placentation and related maternal morbidities, MNT merits inclusion within the MVM pathologic spectrum. Consistent reporting of MNTs >2 mm in size is recommended, as these lesions correlate with other MVM lesions and MVM-predisposing morbidities. Other lesions, particularly DLN and ETI, lacked such association questioning their diagnostic utility.

Ventricular fibrillation due to coronary spasm after pepper spray.

Pepper spray is used as a crowd control agent and for self-defense. It has been thought to be safe; however, 27 persons have died in police custody after exposure to pepper spray. We report on a 21-year-old man, with no underlying heart disease and a normal ECG and echocardiogram in the past, who was pepper sprayed and developed ventricular fibrillation. An admission ECG showed marked ST segment elevation but subsequent coronary arteriography was normal. We hypothesize that pepper spray triggered coronary spasm, resulting in ventricular fibrillation. This report adds to a body of information that pepper spray is dangerous.