Polymicrobial odontogenic periorbital and orbital necrotizing fasciitis (PONF): A case report.

Purpose: To present a case of periorbital and orbital necrotizing fasciitis (PONF) from an odontogenic source with a distinct microbiologic profile and highlight the need for emergent multidisciplinary management. Observations: A 39-year-old man presented with periorbital swelling, pain, and erythema following facial trauma. Imaging revealed peri-dental collections, accompanying maxillary sinusitis, and pre- and post-septal involvement. Immediate surgical debridement of necrotic tissue along with broad-spectrum antibiotics were pursued for management. Cultures grew multiple organisms, most notably Streptococcus milleri group and Staphylococcus lugdunensis. Conclusions and Importance: PONF is a rare yet potentially fatal disease. Streptococcus milleri group and a fulminant course are to be suspected when the source is odontogenic. Timely multidisciplinary surgical debridement and medical management with intravenous antibiotics is critical for best outcomes

Nocardia sienata: a new causative species of infectious keratitis.

A 25-year-old man presented with a 2-month history of progressively worsening left eye pain and an atypical corneal ring infiltrate. His condition deteriorated despite topical antibiotic therapy. Cultures for bacteria, fungus and acanthamoeba, repeated twice, all demonstrated no growth. On third corneal scraping, culture on Middlebrook agar grew colonies after 3 weeks of incubation. Sixteen-second deep sequencing identified Nocardia sienata as the pathogen. This species of Nocardia has not previously been described as a causative pathogen for infectious keratitis. Sloughing and loose epithelium with recurrent filament formation are unusual in infectious keratitis and could be associated with this species. In culture-negative cases, clinicians should consider Nocardia as a cause of keratitis despite its rarity outside of south Asia and use steroids cautiously. Next generation sequencing technology may facilitate identification of the causate of keratitis and can be especially useful in culture-negative cases and with unexpected pathogens

Keratoprosthesis, silicone oil placement, and fluocinolone acetonide implant for treatment of uveitis-associated hypotony and keratopathy.

PurposeTo describe a case series of combined Boston Type 1 Keratoprosthesis with pars plana vitrectomy, silicone oil placement, and fluocinolone acetonide intravitreal 0.59 mg implant (RETISERT®), and report its safety and efficacy in preventing phthisis bulbi in patients with uveitis-associated hypotony and concurrent corneal edema.FindingsA retrospective review of patients with chronic uveitis, corneal decompensation and concurrent hypotony who underwent the combined approach described here between 2015 and 2020 was conducted. Three patients were treated using the combined approach. Post-operative recovery was unremarkable in all cases and the patients' corneal condition remained stable on follow up. No patient developed phthisis, retroprosthetic membrane, or infectious endophthalmitis. Average intraocular pressure one year after intervention was 2.7 to 6.4 mmHg higher compared to a year prior.ConclusionsThe approach described is potentially safe and effective in preventing phthisis and membrane formation in uveitis-associated hypotony and keratopathy

Multifocal pancreatic PPoma in the setting of MEN1: Case report and review of literature.

Introduction and importanceFunctioning pancreatic neuroendocrine tumors (pNETs) that express pancreatic polypeptide-PPomas-do not yet have a pathognomonic clinical syndrome associated with them due to their overall rarity and diverse symptoms. Moreover, in patients with MEN1, the often multifocal nature of pNETs presents a unique clinical issue.Case presentationWe report a case of a 22-year-old man with a known MEN1 gene mutation who was suffering from severe diarrhea (7-8 bowel movements per day) and was found to have only elevated PP levels on biochemical work-up. Ga68-DOTATATE PET/CT showed multifocal tumors in the body and tail of the pancreas that were not evident on contrast-enhanced CT. The patient underwent a successful laparoscopic radical antegrade modular pancreatosplenectomy (RAMP) and recovered well post-operatively with complete resolution of his diarrhea. Immunohistochemistry showed multiple pure PPomas.Clinical discussionThis case highlights the unique propensity for multifocal disease in patients with MEN1 mutations and the utility of functional imaging by somatostatin analogs, i.e., Ga68-DOTATATE PET/CT, in order to perform oncologic laparoscopic pancreatic resections.ConclusionPPomas in the setting of MEN1 mutations are a unique clinical entity due to their diverse associated clinical syndromes and propensity for multifocal disease

Sequential regression and simulation: a method for estimating causal effects from heterogeneous clinical trials without a common control group

BackgroundThe advent of clinical trial data sharing platforms has created opportunities for making new discoveries and answering important questions using already collected data. However, existing methods for meta-analyzing these data require the presence of shared control groups across studies, significantly limiting the number of questions that can be confidently addressed. We sought to develop a method for meta-analyzing potentially heterogeneous clinical trials even in the absence of a common control group.MethodsThis work was conducted within the context of a broader effort to study comparative efficacy in Crohn's disease. Following a search of clnicaltrials.gov we obtained access to the individual participant data from nine trials of FDA-approved treatments in Crohn's Disease (N = 3392). We developed a method involving sequences of regression and simulation to separately model the placebo- and drug-attributable effects, and to simulate head-to-head trials against an appropriately normalized background. We validated this method by comparing the outcome of a simulated trial comparing the efficacies of adalimumab and ustekinumab against the recently published results of SEAVUE, an actual head-to-head trial of these drugs. This study was pre-registered on PROSPERO (#157,827) prior to the completion of SEAVUE.ResultsUsing our method of sequential regression and simulation, we compared the week eight outcomes of two virtual cohorts subject to the same patient selection criteria as SEAVUE and treated with adalimumab or ustekinumab. Our primary analysis replicated the corresponding published results from SEAVUE (p = 0.9). This finding proved stable under multiple sensitivity analyses.ConclusionsThis new method may help reduce the bias of individual participant data meta-analyses, expand the scope of what can be learned from these already-collected data, and reduce the costs of obtaining high-quality evidence to guide patient care

A Triple-Fluorophore-Labeled Nucleic Acid pH Nanosensor to Investigate Non-viral Gene Delivery.

There is a need for new tools to better quantify intracellular delivery barriers in high-throughput and high-content ways. Here, we synthesized a triple-fluorophore-labeled nucleic acid pH nanosensor for measuring intracellular pH of exogenous DNA at specific time points in a high-throughput manner by flow cytometry following non-viral transfection. By including two pH-sensitive fluorophores and one pH-insensitive fluorophore in the nanosensor, detection of pH was possible over the full physiological range. We further assessed possible correlation between intracellular pH of delivered DNA, cellular uptake of DNA, and DNA reporter gene expression at 24 hr post-transfection for poly-L-lysine and branched polyethylenimine polyplex nanoparticles. While successful transfection was shown to clearly depend on median cellular pH of delivered DNA at the cell population level, surprisingly, on an individual cell basis, there was no significant correlation between intracellular pH and transfection efficacy. To our knowledge, this is the first reported instance of high-throughput single-cell analysis between cellular uptake of DNA, intracellular pH of delivered DNA, and gene expression of the delivered DNA. Using the nanosensor, we demonstrate that the ability of polymeric nanoparticles to avoid an acidic environment is necessary, but not sufficient, for successful transfection