Surface-Controlled Sialoside-Based Biosensing of Viral and Bacterial Neuraminidases.

Neuraminidases (NA) are sialic acid-cleaving enzymes that are used by both bacteria and viruses. These enzymes have sialoside structure-related binding and cleaving preferences. Differentiating between these enzymes requires using a large array of hard-to-access sialosides. In this work, we used electrochemical impedimetric biosensing to differentiate among several pathogene-related NAs. We used a limited set of sialosides and tailored the surface properties. Various sialosides were grafted on two different surfaces with unique properties. Electrografting on glassy carbon electrodes provided low-density sialoside-functionalized surfaces with a hydrophobic submonolayer. A two-step assembly on gold electrodes provided a denser sialoside layer on a negatively charged submonolayer. The synthesis of each sialoside required dozens of laborious steps. Utilizing the unique protein-electrode interaction modes resulted in richer biodata without increasing the synthetic load. These principles allowed for profiling NAs and determining the efficacy of various antiviral inhibitors.

The Rare Presentation of Multiple Chondroid Syringomas in One Patient: A Case Report.

Chondroid syringomas are rare, benign tumors originating from sweat glands occurring as singular lesions of the head and neck. This case report presents a patient in whom multiple chondroid syringoma lesions were found. Thus illuminating the possibility for such occurrences in the future of which physicians should be aware.

Biocatalysis versus Molecular Recognition in Sialoside-Selective Neuraminidase Biosensing.

Sialic acid recognition and hydrolysis are essential parts of cellular function and pathogen infectivity. Neuraminidases are enzymes that detach sialic acid from sialosides, and their inhibition is a prime target for viral infection treatment. The connectivity and type of sialic acid influence the recognition and hydrolysis activity of the many different neuraminidases. The common strategies to evaluate neuraminidase activity, recognition, and inhibition rely on extensive labeling and require a large amount of sialylated glycans. The above limitations make the effort of finding viral inhibitors extremely difficult. We used synthetic sialylated glycans and developed a label-free electrochemical method to show that sialoside structural features lead to selective neuraminidase biosensing. We compared Neu5Ac to Neu5Gc sialosides to evaluate the organism-dependent neuraminidase selectivity-sensitivity relationship. We demonstrated that the type of surface and the glycan monolayer density direct the response to either binding or enzymatic activity. We proved that while the hydrophobic glassy carbon surface increases the interaction with the enzyme hydrophobic interface, the negatively charged interface of the lipoic acid monolayer on gold repels the protein and enables biocatalysis. We showed that the sialoside monolayers can serve as tools to evaluate the inhibition of neuraminidases both by biocatalysis and molecular recognition.

Cutaneous metastasis of PD-L1 positive cervical carcinoma.

•Cutaneous metastases in cervical cancer are rare and associated with a poor prognosis.•Treatment is typically palliative, utilizing chemotherapy and radiation.•We report a case of PD-L1 positive cervical cancer with cutaneous metastases that developed after initial recurrence.•For patients on checkpoint inhibitor therapy who develop skin toxicity, it is important to rule out cutaneous metastases.

Evaluation of the incidence and clinical significance of WT-1 expression in uterine serous carcinoma.

BACKGROUND: Wilms tumor gene 1 (WT1) expression is a hallmark of ovarian serous carcinoma and considered to be diagnostic marker of these tumors, differentiating them from uterine serous carcinoma (USC), historically thought to rarely express WT1. However, more recent data indicates a significant percentage of USC may express WT1. The clinical implications of WT1 positivity in USC remain unclear. METHODS: A multicenter retrospective analysis of patients with USC was conducted from 2000 to 2019. Inclusion criteria were patients who had undergone comprehensive surgical staging/tumor debulking with archival tissue available for WT1 assessment via immunohistochemistry (IHC). Chemosensitive patients were defined as those recurring >6 months from last platinum-based chemotherapy. Progression free survival (PFS) and overall survival (OS) analysis was performed using Kaplan-Meier estimates. Multivariate analysis (MVA) was performed using Cox proportional hazards model. RESULTS: WT1 status was evaluated in 61 patients with USC. 13 (21.3%) were positive for WT1 by IHC. Stage distribution included 32% stage I, 5% stage II, 25% stage III and 38% stage IV. There was no difference in the stage (p = 0.158), race (p = 0.227) or distribution of recurrence sites (p = 0.581) between WT1 positive and WT1 negative tumors. The majority of patients were chemosensitive (63%). Chemosensitivity was significantly improved in WT1 positive (92.3%) vs. WT1 negative tumors (55.8%) (p = 0.016). We observed a trend towards improved PFS among WT1 positive tumors (21 vs. 16-months, respectively) (p = 0.544). On MVA, stage (p < 0.001) and chemosensitivity (p < 0.001) were independent predictors of PFS. CONCLUSIONS: WT1 positivity is observed in over 20% of USC. WT1 expression is associated with improved chemosensitivity which may contribute to improvements in PFS.

Hofbauer Cells and COVID-19 in Pregnancy.

CONTEXT.­: SARS-CoV-2 can undergo maternal-fetal transmission, heightening interest in the placental pathology findings from this infection. Transplacental SARS-CoV-2 transmission is typically accompanied by chronic histiocytic intervillositis together with necrosis and positivity of syncytiotrophoblast for SARS-CoV-2. Hofbauer cells are placental macrophages that have been involved in viral diseases, including HIV and Zika virus, but their involvement in SARS-CoV-2 is unknown. OBJECTIVE.­: To determine whether SARS-CoV-2 can extend beyond the syncytiotrophoblast to enter Hofbauer cells, endothelium, and other villous stromal cells in infected placentas of liveborn and stillborn infants. DESIGN.­: Case-based retrospective analysis by 29 perinatal and molecular pathology specialists of placental findings from a preselected cohort of 22 SARS-CoV-2-infected placentas delivered to pregnant women testing positive for SARS-CoV-2 from 7 countries. Molecular pathology methods were used to investigate viral involvement of Hofbauer cells, villous capillary endothelium, syncytiotrophoblast, and other fetal-derived cells. RESULTS.­: Chronic histiocytic intervillositis and trophoblast necrosis were present in all 22 placentas (100%). SARS-CoV-2 was identified in Hofbauer cells from 4 of 22 placentas (18.2%). Villous capillary endothelial staining was positive in 2 of 22 cases (9.1%), both of which also had viral positivity in Hofbauer cells. Syncytiotrophoblast staining occurred in 21 of 22 placentas (95.5%). Hofbauer cell hyperplasia was present in 3 of 22 placentas (13.6%). In the 7 cases having documented transplacental infection of the fetus, 2 (28.6%) occurred in placentas with Hofbauer cell staining positive for SARS-CoV-2. CONCLUSIONS.­: SARS-CoV-2 can extend beyond the trophoblast into the villous stroma, involving Hofbauer cells and capillary endothelial cells, in a small number of infected placentas. Most cases of SARS-CoV-2 transplacental fetal infection occur without Hofbauer cell involvement.

Histologic and Immunohistochemical Evaluation of 65 Placentas From Women With Polymerase Chain Reaction-Proven Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection.

CONTEXT.­: Coronavirus disease 2019 (COVID-19) has been shown to have effects outside of the respiratory system. Placental pathology in the setting of maternal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remains a topic of great interest because earlier studies have shown mixed results. OBJECTIVE.­: To ascertain whether maternal SARS-CoV-2 infection is associated with any specific placental histopathology, and to evaluate the virus's propensity for direct placental involvement. DESIGN.­: Placentas from 65 women with polymerase chain reaction-proven SARS-CoV-2 infection underwent histologic evaluation using Amsterdam consensus group criteria and terminology. Another 85 placentas from women without SARS-CoV-2 constituted the negative control group. A total of 64 of the placentas from the SARS-CoV-2-positive group underwent immunohistochemical staining for SARS-CoV-2 nucleocapsid protein. RESULTS.­: Pathologic findings were divided into maternal vascular malperfusion, fetal vascular malperfusion, chronic inflammatory lesions, amniotic fluid infection sequence, increased perivillous fibrin, intervillous thrombi, increased subchorionic fibrin, meconium-laden macrophages (M-LMs) within fetal membranes, and chorangiosis. There was no statistically significant difference in prevalence of any specific placental histopathology between the SARS-CoV-2-positive and SARS-CoV-2-negative groups. There was no immunohistochemical evidence of SARS-CoV-2 virus in any of the 64 placentas that underwent staining for viral nucleocapsid protein. CONCLUSIONS.­: Our study results and a literature review suggest that there is no characteristic histopathology in most placentas from women with SARS-CoV-2 infection. Likewise, direct placental involvement by SARS-CoV-2 is a rare event.

Multiple malignant transformations of an ovarian mature cystic teratoma.

BACKGROUND: Malignant transformation of mature cystic teratomas (MCTs) is a rare phenomenon. The most common histology of a malignant transformation is squamous cell carcinoma, and there are limited reports of multiple malignancies arising in a single MCT. Further data are necessary to guide management of these atypical cases. CASE: We present the case of a 48-year-old with MCT containing a malignant papillary thyroid carcinoma (PTC) arising in the context of struma ovarii and a carcinoid tumour. CONCLUSION: Malignant transformations of MCTs are exceedingly rare with no guidelines on management. We use this case to demonstrate an approach for the workup and management of malignantly transformed MCTs.

Weights of Fetal Membranes and Umbilical Cords: Correlation With Placental Pathology.

INTRODUCTION: Proper placental gross examination requires weighing the placental disc trimmed of fetal membranes and the umbilical cord. However, untrimmed placental weights are often reported, both in cases submitted for consultation and in publications. Thus, determining the contribution of membranes and cords to untrimmed placental weights would be helpful in estimating the true trimmed weight of placentas. We sought to report the average weights of membranes and cord in term placentas and to correlate these weights with common placental pathologies. METHODS: A total of 500 consecutive placentas delivered between 36 and 42 weeks gestational age were subjected to a modified grossing protocol, in which the weight of the trimmed and untrimmed placentas, fetal membranes, and umbilical cords were recorded. Acute chorioamnionitis, meconium, maternal vascular malperfusion, and fetal vascular malperfusion were included as pathologic correlates. Clinical data such as the presence of fetal hydrops, intrauterine growth restriction, intrauterine fetal demise, and maternal diabetes were also recorded. RESULTS: The mean weights of the trimmed placenta, fetal membranes, and umbilical cords were 442 g (180-805 g), 47.2 g (16-108 g), and 37.9 g (9-126 g), respectively. The fetal membranes and umbilical cord weights contributed a mean of 16% to the total untrimmed placental weight. Meconium was associated with heavier fetal membranes. Fetal vascular malperfusion was associated with longer umbilical cord and thus also with heavier umbilical cords. Maternal vascular malperfusion and intrauterine growth restriction were associated with lighter placentas. DISCUSSION: The trimmed placental disc weight may be estimated by subtracting 16% (ie, weight of the fetal membranes and umbilical cord) from the untrimmed placental weight, or alternatively by subtracting the mean weight of the membranes and umbilical cord. It is important to consider the effects of meconium, fetal and maternal vascular malperfusion, and intrauterine growth restriction on membrane and cord weights when estimating the trimmed placental disc weight.

Do Serum Creatinine Levels Show Clinically Significant Fluctuations on Serial Determinations on the Siemens Advia 1800 Analyzer?

BACKGROUND: The goal of this work was to determine whether there are clinically significant fluctuations in the level of serum creatinine on serial determinations, especially in the borderline range (1.1-1.3 mg/dl), after specimen storage. METHODS: Sixty-one serum samples were analyzed. They were divided into three categories based on the initial serum creatinine measurement: low (≤1.0 mg/dl), borderline (1.1-1.3 mg/dl), and high (≥1.4 mg/dl). The specimens were stored at 4°C and run on the Siemens Advia 1800 chemistry analyzer on days 1, 3, and 11. RESULTS: Statistical comparisons of the three groups were made using the unpaired t-test, yielding a two-tailed P-value for each group comparison. The P-values ranged from 0.0829 to 0.3892, indicating no statistically significant difference between the standard deviations of each group. CONCLUSIONS: Mild-to-moderate fluctuations in precision occur in successive serum creatinine determinations. The overwhelming majority of these fluctuations should not affect clinical decision making.

Cryoglobulinemia in a patient with chronic lymphocytic leukemia - A case report and review of literature of renal involvement in CLL.

The incidence of glomerulonephritis, as a manifestation of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), has always been considered low. Though renal infiltration is usually detected at post-mortem, it does not often interfere with kidney function [1]. Though immunoglobulin (Ig) levels in most CLL patients are subnormal, small monoclonal Ig peaks are occasionally detected in serum. They were present in a number of reported CLL nephropathy patients, and not all were cryoglobulins; serum and glomerular staining were concordant for Ig type [2,3,4]. Myeloma, which secretes monoclonal light chains, causes nephropathy in 25% of patients. But the little presumably secreted by small plasma cell clones, without myeloma, may also be nephrotoxic. The same is true of the low secretory CLL cells, which may occasionally be associated with cryoglobulins and other nephrotoxic Igs [5]. We report a patient with early stage CLL (Rai stage 0) with cryoglobulins, which led to membranoproliferative glomerulonephritis (MPGN), and death. We located reports of 51 patients with CLL-associated nephrotic syndrome or nephropathy, mostly from MPGN related to local Ig deposits. In those patients screened for cryoglobulins, about half tested positive. Many were early stage cases, where MPGN developed long after CLL presentation, and responded to its treatment. As early diagnosis and treatment CLL-related nephropathy may be curative, we propose a prospective study to determine the incidence of hyperalbuminuria development after presentation.