Background Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX). Methods In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung–Knapp–Sidik–Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. Results A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. Conclusions Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care.

No abstract

A significant proportion of ductal carcinomas in situ (DCISs) of the breast diagnosed on core biopsies had invasion upon excision. An assessment of various invasion predictors in the biopsies yielded conflicting results. A cohort of 157 cases with needle core biopsy diagnosed with DCISs (including 109 histologically proven DCISs, and 48 cases with invasion upon excision) were evaluated for the numbers of positive and total cores, the percentage of positivity, lobular cancerization, tumor nuclear grade, necrosis, calcification, predominate histological pattern, lymphocytic infiltrate and excisional tumor size. The mean positive core percentage and excisional tumor size were 76% and 2.8 cm for invasive and 66% and 1.9 cm for noninvasive groups. In the biopsy of the invasive group, cancerization of lobules was present in 52%, and nuclear grades 1, 2 and 3 were present in 31, 31 and 38%, respectively. Large comedo and small noncomedo necroses were present in 48 and 10%, whereas large and small calcifications were present in 16 and 21%. Solid, cribriform and papillary patterns were observed in 88, 38 and 21%, respectively. Moderate to marked lymphoid infiltrate was present in 31%. In the biopsy of the noninvasive group, cancerization of lobules was present in 69%, and the nuclear grades 1, 2 and 3 were present in 23, 48 and 29%, respectively. Large comedo and small noncomedo necroses were present in 35 and 11%, whereas large and small calcifications were present in 33 and 23%. Solid, cribriform and papillary patterns were observed in 85, 39 and 9%, respectively. Moderate to marked lymphoid infiltrate was present in 36%. Comparing these groups, a higher positive core percentage, papillary pattern and less cancerization of lobules in the cores and larger excisional tumor size were associated with a higher chance of invasion. Calcification, necrosis and nuclear grade were not significant invasion predictors.

X-linked Dystonia-Parkinsonism (XDP) is a neurodegenerative disease linked to an insertion of a SINE-VNTR-Alu (SVA)-type retrotransposon within an intron of TAF1. This SVA insertion induces aberrant TAF1 splicing and partial intron retention, thereby decreasing levels of the full-length transcript. Here we sought to determine if these altered transcriptional dynamics caused by the SVA are also accompanied by local changes in histone acetylation, given that these modifications influence gene expression. Because TAF1 protein may itself exhibit histone acetyltransferase activity, we also examined whether decreased TAF1 expression in XDP cell lines and post-mortem brain affects global levels of acetylated histone H3 (AcH3). The results demonstrate that total AcH3 are not altered in XDP post-mortem prefrontal cortex or cell lines. We also did not detect local differences in AcH3 associated with TAF1 exons or intronic sites flanking the SVA insertion. There was, however, a decrease in AcH3 association with the exon immediately proximal to the intronic SVA, and this decrease was normalized by CRISPR/Cas-excision of the SVA. Collectively, these data suggest that the SVA insertion alters histone status in this region, which may contribute to the dysregulation of TAF1 expression.

Primary sinonasal ameloblastoma is an extremely rare odontogenic epithelial tumor histomorphologically identical to its gnathic counterparts but with distinct epidemiologic and clinicopathologic characteristics. We present a case of a 46 female with a 1 year history of recurrent epistaxis, nasal obstruction, and frontonasal headache. Clinical examination, CT scan, and subsequent surgical excsion revealed an intranasal mass attached to the lateral nasal cavity with histomorphologic features of ameloblastoma and was signed out as extragnathic soft tissue ameloblastoma of the sinonasal area. Extraosseous extragnathic primary sinonasal ameloblastoma are rare but do occur and should be distinguished from infrasellar craniopharyngiomas.   Keywords: Extraosseous, Extragnathic, Sinonasal, Ameloblastoma                   Ameloblastomas are slow growing locally aggressive odontogenic epithelial tumors of the jaw and are classified into solid/multicystic, unicystic, desmoplastic, and peripheral subtypes.1,2,3 They involve the mandible 80% of the time and are often associated with an unerrupted molar tooth. Extraosseous extragnathic Ameloblastomas are very rare, occurring less than 1.3 to 10% of all ameloblastomas, with all cases reported so far arising from the sinonasal region.1,2,4 We present a case of primary sinonasal ameloblastoma in a Filipino female. Case Report               A 46-year old female consulted at the University of the Philippines - Philippine General Hospital Department of Otorhinolayngology with a one year history of recurrent, spontaneous epistaxis from the right nose, associated with ipsilateral nasal obstruction, thin-brown rhinorrhea, and frontonasal headache relieved by oral paracetamol. Nasal endoscopy revealed a pale pink irregularly shaped polypoid mass attached to the lateral nasal wall, almost completely obstructing the nasal cavity. Plain coronal and sagittal CT images of the nasal cavity and paranasal sinuses showed opacification of the right nasal chamber by soft tissue densities with obstruction of the ipsilateral ostiomeatal unit and sphenoethmoidal recess (Figure 1). The sphenoid, frontal and contralateral paranasal sinuses and nasal vault were uninvolved. Incision biopsy was read as sinonasal exophytic papilloma and the mass was excised via endoscopic sinus surgery under general anesthesia. The submitted specimen consisted of a 2 cm by 0.8 cm cream white solid, soft to rubbery mass. On histologic examination, trabecula and islands of cytologically benign odontogenic epithelium permeate an edematous, myxoid, hypocellular stroma. Columnar cells that display palisading and reverse polarity, line the periphery of the epithelium. At the center of the epithelial islands, loose collections of stellate and spindly cells, similar to the stellate reticulum of the embryonic enamel organ, are found. Acanthomatous changes are present in the superficial layers. There is no atypia and no mitosis (Figures 2 and 3). This case was signed out as extragnathic soft tissue ameloblastoma. Discussion               Most reported cases of ameloblastoma in the sinonasal cavity actually describe tumors that originated from the maxilla and have only secondarily involved the sinonasal area.4 To date, the 26-year review by Schafer et al. of 24 primary sinonasal tract ameloblastomas at the Armed Forces Institute of Pathology remains the single largest series describing this entity.4 Although three additional case reports were recently published, to the best of our knowledge, this is the 1st case of primary sinonasal ameloblastoma in the Philippines.5,6,7 Unlike our patient, primary sinonasal ameloblastomas more commonly affect males with mean age at presentation of 59.7 years.1,4 Patients usually present with an intranasal mass, nasal obstruction, sinusitis and epistaxis of 1 month to several years duration.1,4 Radiologically, sinonasal ameloblastomas are solid masses or opacifications rather than multilocular and radiolucent as those that arise within the jaws.1 The histomorphologic features of primary sinonasal ameloblastomas are identical to their gnathic counterparts and include unencapsulated proliferating nests, islands or sheets of odontogenic epithelium resembling the embryonic enamel organ. The epithelium is composed of a central area of loosely arranged cells similar to the stellate reticulum of the enamel organ and a peripheral layer of palisading columnar or cuboidal cells with hyperchromatic small nuclei oriented away from the basement membrane, the so called reverse polarity.1 Experts believe that primary sinonasal ameloblastomas arise from remnants of odontogenic epithelium, lining of odontogenic cysts, basal layer of the overlying oral mucosa, or heterotopic embryonic organ epithelium.1,4 This is supported by the observation that the ameloblastomatous epithelial proliferations are often seen in continuity with native sinonasal (schneiderian) epithelium.1,4 This entity should be distinguished from an infrasellar craniopharyngioma, which is an important differential diagnosis that is often difficult and often virtually impossible to differentiate from a primary sinonasal ameloblastoma solely on histomorphologic grounds. In most cases, however, clinicopathologic correlation guides the diagnosis8 and special stains are of limited utility.1  Surgical excision is the treatment of choice, the type and extent of which is dictated by the size and localization of the lesion. Recurrence can occur, generally within 2 years, but overall treatment success depends on complete surgical eradication. No deaths, metastases, or malignant transformation have so far been reported1,4 and our patient is free of disease, fifteen months post surgery.