Modeling the complete kinetics of coxsackievirus B3 reveals human determinants of host-cell feedback Graphical abstract Highlights d A complete kinetic model of acute infection by the coxsackievirus B3 enterovirus d Enteroviral replication organelles accelerate biochemistry on membrane surfaces d Type I interferon exaggerates different enteroviral susceptibilities of host cells d A common polymorphism in MAVS alters host-cell susceptibility to coxsackievirus B3

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Background Abdominal access during ventriculoperitoneal (VP) shunt insertion has historically been obtained by neurosurgeons via an open abdominal approach. With recent advances in laparoscopy, neurosurgeons frequently consult general surgery for aid during the procedure. The goal of this study is to identify if laparoscopic assistance improves the overall outcomes of the procedure. Methods This retrospective study included all patients who underwent open or laparoscopic VP shunt placement between September 2012 and August 2020 at our tertiary referral hospital. Patient demographics, comorbidities, prior history of abdominal surgery, open vs. laparoscopic insertion, operation time, and complications within 30 days were obtained. Results Neurosurgery placed 107 shunts using an open abdominal technique and general surgery placed 78 using laparoscopy. The average OR time in minutes was 75.5 minutes for the open cohort and 61.8 for the laparoscopic cohort ( p = 0.006). In patients without a history of abdominal surgery, the average OR time in minutes was 79.4 in the open cohort and 57.1 in the laparoscopic cohort ( p = 0.015). The postoperative shunt infection rate was 10.2% in the open group and 3.8% in the laparoscopic group ( p = 0.077). Discussion Laparoscopic placement of VP shunts is a reasonable alternative to open placement and results in shorter OR times. There is also a trend toward few infections in the laparoscopic placement. There appears to be an advantage with a team approach and laparoscopic placement of the peritoneal portion of the shunt.

SUMMARYComplete kinetic models are pervasive in chemistry but lacking in biological systems. We encoded the complete kinetics of infection for coxsackievirus B3 (CVB3), a compact and fastacting RNA virus. The kinetics are built from detailed modules for viral binding–delivery, translation–replication, and encapsidation. Specific module activities are dampened by the type I interferon response to viral double-stranded RNAs (dsRNAs), which is itself disrupted by viral proteinases. The validated kinetics uncovered that cleavability of the dsRNA transducer mitochondrial antiviral signaling protein (MAVS) becomes a stronger determinant of viral outcomes when cells receive supplemental interferon after infection. Cleavability is naturally altered in humans by a common MAVS polymorphism, which removes a proteinase-targeted site but paradoxically elevates CVB3 infectivity. These observations are reconciled with a simple nonlinear model of MAVS regulation. Modeling complete kinetics is an attainable goal for small, rapidly infecting viruses and perhaps viral pathogens more broadly.

Trichosporon asahii is an opportunistic fungus that forms septate hyphae and pseudohyphae, resembling Candida albicans, and causes fungemia in susceptible individuals. Risk factors for T. asahii infection include immunosuppression, IV catheters, and malignancy. In the present case, a 67-year-old male with a history of renal transplant on immunosuppressive therapy was hospitalized for coronavirus disease 2019 (COVID-19) pneumonia. Despite treatment with steroids and broad initial antibiotic coverage with cefepime, doxycycline, and vancomycin, the patient underwent continual respiratory decline. His sputum culture on hospital day 10 was positive for non-candidal yeast, and despite subsequent appropriate empiric coverage with micafungin and amphotericin B, the patient continued to decline and ultimately died due to the resistance of T. asahii to these antifungals. This case highlights the importance of suspecting T. asahii as an infectious cause in patients whose cultures show non-candidal yeast and initiating appropriate antifungal treatment early in their treatment course.