Mycobacterium abscessus Cluster in Cardiac Surgery Patients Potentially Attributable to a Commercial Water Purification System.

BACKGROUND: Nontuberculous mycobacteria are water-avid pathogens that are associated with nosocomial infections. OBJECTIVE: To describe the analysis and mitigation of a cluster of Mycobacterium abscessus infections in cardiac surgery patients. DESIGN: Descriptive study. SETTING: Brigham and Women's Hospital, Boston, Massachusetts. PARTICIPANTS: Four cardiac surgery patients. INTERVENTION: Commonalities among cases were sought, potential sources were cultured, patient and environmental specimens were sequenced, and possible sources were abated. MEASUREMENTS: Description of the cluster, investigation, and mitigation. RESULTS: Whole-genome sequencing confirmed homology among clinical isolates. Patients were admitted during different periods to different rooms but on the same floor. There were no common operating rooms, ventilators, heater-cooler devices, or dialysis machines. Environmental cultures were notable for heavy mycobacterial growth in ice and water machines on the cluster unit but little or no growth in ice and water machines in the hospital's other 2 inpatient towers or in shower and sink faucet water in any of the hospital's 3 inpatient towers. Whole-genome sequencing confirmed the presence of a genetically identical element in ice and water machine and patient specimens. Investigation of the plumbing system revealed a commercial water purifier with charcoal filters and an ultraviolet irradiation unit leading to the ice and water machines in the cluster tower but not the hospital's other inpatient towers. Chlorine was present at normal levels in municipal source water but was undetectable downstream from the purification unit. There were no further cases after high-risk patients were switched to sterile and distilled water, ice and water machine maintenance was intensified, and the commercial purification system was decommissioned. LIMITATION: Transmission pathways were not clearly characterized. CONCLUSION: Well-intentioned efforts to modify water management systems may inadvertently increase infection risk for vulnerable patients. PRIMARY FUNDING SOURCE: National Institutes of Health.

Rethinking recovery in adolescent concussions: Network-level functional connectivity alterations associated with motor deficits.

Adolescents who are clinically recovered from concussion continue to show subtle motor impairment on neurophysiological and behavioral measures. However, there is limited information on brain-behavior relationships of persistent motor impairment following clinical recovery from concussion. We examined the relationship between subtle motor performance and functional connectivity of the brain in adolescents with a history of concussion, status post-symptom resolution, and subjective return to baseline. Participants included 27 adolescents who were clinically recovered from concussion and 29 never-concussed, typically developing controls (10-17 years); all participants were examined using the Physical and Neurologic Examination of Subtle Signs (PANESS). Functional connectivity between the default mode network (DMN) or dorsal attention network (DAN) and regions of interest within the motor network was assessed using resting-state functional magnetic resonance imaging (rsfMRI). Compared to controls, adolescents clinically recovered from concussion showed greater subtle motor deficits as evaluated by the PANESS and increased connectivity between the DMN and left lateral premotor cortex. DMN to left lateral premotor cortex connectivity was significantly correlated with the total PANESS score, with more atypical connectivity associated with more motor abnormalities. This suggests that altered functional connectivity of the brain may underlie subtle motor deficits in adolescents who have clinically recovered from concussion. More investigation is required to understand the persistence and longer-term clinical relevance of altered functional connectivity and associated subtle motor deficits to inform whether functional connectivity may serve as an important biomarker related to longer-term outcomes after clinical recovery from concussion.

The Risk of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Transmission from Patients With Undiagnosed Coronavirus Disease 2019 (COVID-19) to Roommates in a Large Academic Medical Center.

We assessed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission between patients in shared rooms in an academic hospital between September 2020 and April 2021. In total, 11 290 patients were admitted to shared rooms, of whom 25 tested positive. Among 31 exposed roommates, 12 (39%) tested positive within 14 days. Transmission was associated with polymerase chain reaction (PCR) cycle thresholds ≤21.

Ralstonia pickettii and Pseudomonas aeruginosa Bloodstream Infections Associated With Contaminated Extracorporeal Membrane Oxygenation Water Heater Devices.

We report on probable factory-based contamination of portable water heaters with waterborne pathogens and 2 bloodstream infections potentially attributable to off-label use of these water heaters to warm extracorporeal membrane oxygenation circuits. Great caution is warranted when using water-based devices to care for critically ill patients.

Rapid Control of Hospital-Based Severe Acute Respiratory Syndrome Coronavirus 2 Omicron Clusters Through Daily Testing and Universal Use of N95 Respirators.

The highly contagious severe acute respiratory syndrome coronavirus 2 Omicron variant increases risk for nosocomial transmission despite universal masking, admission testing, and symptom screening. We report large increases in hospital-onset infections and 2 unit-based clusters. The clusters rapidly abated after instituting universal N95 respirators and daily testing. Broader use of these strategies may prevent nosocomial transmissions.

Cluster of Burkholderia cepacia Complex Infections Associated With Extracorporeal Membrane Oxygenation Water Heater Devices.

BACKGROUND: Burkholderia cepacia complex is a group of potential nosocomial pathogens often linked to contaminated water. We report on a cluster of 8 B. cepacia complex infections in cardiothoracic intensive care unit patients, which were attributed to contaminated extracorporeal membrane oxygenation (ECMO) water heaters. METHODS: In December 2020, we identified an increase in B. cepacia complex infections in the cardiothoracic intensive care unit at Brigham and Women's Hospital. We sought commonalities, sequenced isolates, obtained environmental specimens, and enacted mitigation measures. RESULTS: Whole-genome sequencing of 13 B. cepacia complex clinical specimens between November 2020 and February 2021 identified 6 clonally related isolates, speciated as Burkholderia contaminans. All 6 occurred in patients on ECMO. Microbiology review identified 2 additional B. contaminans cases from June 2020 that may have also been cluster related, including 1 in a patient receiving ECMO. All 8 definite or probable cluster cases required treatment; 3 patients died, and 3 experienced recurrent infections. After ECMO was identified as the major commonality, all 9 of the hospital's ECMO water heaters were cultured, and B. contaminans grew in all cultures. Cultures from air sampled adjacent to the water heaters were negative. Water heater touch screens were culture positive for B. contaminans, and the sink drain in the ECMO heater reprocessing room also grew clonal B. contaminans. Observations of reprocessing revealed opportunities for cross-contamination between devices through splashing from the contaminated sink. The cluster was aborted by removing all water heaters from clinical service. CONCLUSIONS: We identified a cluster of 8 B. cepacia complex infections associated with contaminated ECMO water heaters. This cluster underscores the potential risks associated with water-based ECMO heaters and, more broadly, water-based care for vulnerable patients.

A SARS-CoV-2 Cluster in an Acute Care Hospital.

BACKGROUND: Little is known about clusters of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in acute care hospitals. OBJECTIVE: To describe the detection, mitigation, and analysis of a large cluster of SARS-CoV-2 infections in an acute care hospital with mature infection control policies. DESIGN: Descriptive study. SETTING: Brigham and Women's Hospital, Boston, Massachusetts. PARTICIPANTS: Patients and staff with cluster-related SARS-CoV-2 infections. INTERVENTION: Close contacts of infected patients and staff were identified and tested every 3 days, patients on affected units were preemptively isolated and repeatedly tested, affected units were cleaned, room ventilation was measured, and specimens were sent for whole-genome sequencing. A case-control study was done to compare clinical interactions, personal protective equipment use, and breakroom and workroom practices in SARS-CoV-2-positive versus negative staff. MEASUREMENTS: Description of the cluster, mitigation activities, and risk factor analysis. RESULTS: Fourteen patients and 38 staff members were included in the cluster per whole-genome sequencing and epidemiologic associations. The index case was a symptomatic patient in whom isolation was discontinued after 2 negative results on nasopharyngeal polymerase chain reaction testing. The patient subsequently infected multiple roommates and staff, who then infected others. Seven of 52 (13%) secondary infections were detected only on second or subsequent tests. Eight of 9 (89%) patients who shared rooms with potentially contagious patients became infected. Potential contributing factors included high viral loads, nebulization, and positive pressure in the index patient's room. Risk factors for transmission to staff included presence during nebulization, caring for patients with dyspnea or cough, lack of eye protection, at least 15 minutes of exposure to case patients, and interactions with SARS-CoV-2-positive staff in clinical areas. Whole-genome sequencing confirmed that 2 staff members were infected despite wearing surgical masks and eye protection. LIMITATION: Findings may not be generalizable. CONCLUSION: SARS-CoV-2 clusters can occur in hospitals despite robust infection control policies. Insights from this cluster may inform additional measures to protect patients and staff. PRIMARY FUNDING SOURCE: None.

Altered white matter diffusivity and subtle motor function in a pilot cohort of adolescents with sports-related concussion.

BACKGROUND AND OBJECTIVE: Adolescents with sports-related concussion (SRC) demonstrate acute and persistent deficits in subtle motor function. However, there is limited research examining related neurological underpinnings. This pilot study examined changes in motor-associated white matter pathways using diffusion tensor imaging (DTI) and their relationship with subtle motor function. METHODS: Twelve adolescents with SRC (12-17 years) within two-weeks post-injury and 13 never-injured neurotypical peers completed DTI scanning. A subset of 6 adolescents with SRC returned for a follow-up visit post-medical clearance from concussion. Subtle motor function was evaluated using the Physical and Neurological Examination of Subtle Signs (PANESS). RESULTS: Adolescents with SRC showed higher mean diffusivity (MD) of the superior corona radiata and greater subtle motor deficits compared to controls. Across all participants, greater subtle motor deficits were associated with higher (more atypical) MD of the superior corona radiata. Preliminary longitudinal analysis indicated reduction in fractional anisotropy of the corpus callosum but no change in the MD of the superior corona radiata from the initial visit to the follow-up visit post-medical clearance. CONCLUSIONS: These findings support preliminary evidence for a brain-behavior relationship between superior corona radiata microstructure and subtle motor deficits in adolescents with SRC that merits further investigation.

Low Risk of Coronavirus Disease 2019 (COVID-19) Among Patients Exposed to Infected Healthcare Workers.

Many patients are fearful of acquiring coronavirus disease 2019 (COVID-19) in hospitals and clinics. We characterized the risk of COVID-19 among 226 patients exposed to healthcare workers with confirmed COVID-19. One patient may have been infected, suggesting that the risk of COVID-19 transmission from healthcare workers to patients is generally low.

Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) From Asymptomatic and Presymptomatic Individuals in Healthcare Settings Despite Medical Masks and Eye Protection.

We describe 3 instances of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission despite medical masks and eye protection, including transmission despite the source person being masked, transmission despite the exposed person being masked, and transmission despite both parties being masked. Whole genome sequencing confirmed perfect homology between source and exposed persons' viruses in all cases.

Specificity of the ergothioneine transporter natively expressed in HeLa cells.

Ergothioneine is a biologically important compound that has been shown to be transported by the organic cation transporter novel type 1 (OCTN1). Following this discovery, a variety of alternate functions for OCTN1 have been suggested including an integral function in the extra-neuronal cholinergic system. The present study reaffirms the primacy of ergothioneine over these alternate substrates using natively expressed OCTN1 in HeLa cells. Besides the general transport inhibitors, quinidine, verapamil and pyrilamine no other putative substrate inhibited ergothioneine transport significantly, with only a slight inhibition demonstrated by carnitine. Even compounds structurally similar to ergothioneine failed to inhibit ergothioneine uptake, suggesting high selectivity of OCTN1. Ergothioneine was found to be avidly accumulated even at low concentrations (300 nM) by HeLa cells.

Mechanistic Evaluation of Bioorthogonal Decaging with trans-Cyclooctene: The Effect of Fluorine Substituents on Aryl Azide Reactivity and Decaging from the 1,2,3-Triazoline.

Bioorthogonal prodrug activation/decaging strategies need to be selective, rapid and release the drug from the masking group upon activation. The rates of the 1,3-dipolar cycloaddition between a trans-cyclooctene (TCO) and a series of fluorine-substituted azido-PABC self-immolative spacers caging two model drugs, and subsequent release from the 1,2,3-triazoline are reported. As the number of fluorine substituents on the PABC linker increases from one to four, the rate of cycloaddition increases by almost one order of magnitude. Using a combination of fluorescence, 1H/19F NMR, and computational experiments, we have been able to determine how substituents on the PABC ring can influence the degradation rates and also the product distribution of the 1,2,3-triazoline. We have also been able to determine how these substituents influence the rate of imine hydrolysis and 1,6-self-immolation decaging rates of the generated anilines. The NMR and computational studies demonstrate that fluorine substituents on the aromatic ring lower the transition state energy required for converting the triazoline to the imine or aziridine intermediates via extrusion of diatomic nitrogen, and that in the case of a tetrafluoro substituted aromatic ring, it is the imine hydrolysis and 1,6-self-immolation that is rate-limiting. This knowledge further enhances the understanding of factors which influence the stability of triazolines, and enables potential applications of fluorinated aromatics, in particular, perfluorinated aromatics, in synthetic chemistry and sustained-release drug delivery systems.

Heterometallic [MnPtn(L)2n](x+) Macrocycles from Dichloromethane-Derived Bis-2-pyridyl-1,2,3-triazole Ligands.

There is continued interest in the assembly of heterometallic metallosupramolecular assemblies due to the potential for new structural types and/or interesting chemical and physical properties. Two novel methylene-linked bis-2-pyridyl-1,2,3-triazole ligands (1a, 1b) were synthesized through CuAAC "click" chemistry between dichloromethane (DCM), sodium azide, and the appropriate ethynylpyridine, giving the shortest possible "regular" bis-pyridyl-1,2,3-triazole. The first example of bis-coordination of two 2-pyridyl-1,2,3-triazoles (Rpytri) around one Pt(II) center is reported, giving exclusive formation of head-to-tail [Pt(Rpytri)2](2+) complexes with vacant binding sites suitable for complexation with other metals and the formation of heterometallic assemblies. The concentration-dependent formation of an equilibrium mixture of a heterometallic [Pd2Pt2(L)4](8+) [4 + 4] square and [Pd3Pt3(L)6](12+) [6 + 6] hexagon was observed, and at lower concentrations ([reactants] = 1.5 mM) hexamer formation was negligible. The [Pt(L)2](2+) building block could also be utilized in the synthesis of a concentration-independent [Cu2Pt2(L)4](6+) metallomacrocyle. These compounds were characterized with (1)H, (13)C, and (1)H DOSY NMR spectroscopies, elemental analysis, mass spectrometry, and in some cases X-ray crystallography.

Quantifying inadvertent thermal bowel injury from the monopolar instrument.

BACKGROUND: Insulation defects are observed in 3-39 % of laparoscopic instruments. Electrosurgical injuries due to insulation defects or capacitive coupling remain an issue in laparoscopic surgery with a prevalence of 0.6-5 per thousand cases. Shielded instruments with active electrode monitoring (AEM) have been postulated to prevent these injuries. The benefit of these instruments has not been quantified. Most bowel injuries are unrecognized intra-operatively. Injury is revealed only after the patient exhibits peritonitis symptoms and surgical intervention to repair the bowel is required. These injuries may result in devastating and costly complications or mortality. The extent of bowel injury possible with commonly used generator settings and associated energy output has never been histologically defined. Our objectives in this experimental study were: quantify and compare the energy released through insulation defects or capacitive coupling with standard unshielded monopolar versus shielded instruments with (AEM), determine energy required to cause a visible burn, and relate the histological burn depth to a given amount of energy. METHODS: Ex vivo porcine jejunum was used for tissue testing. An oscilloscope measured energy output from three common electrosurgical generators at recommended power settings with standard or AEM instruments with insulation defects and in capacitive coupling scenarios. Presence of a visible burn was noted, and depth of tissue damage for a given amount of energy was measured histologically. RESULTS: All samples that received ≥3.8 J of energy had visible burns. As little as 10 J caused full wall thickness burns. 3.8 J was exceeded at the 30- and 50-W power settings in every experimental scenario using standard monopolar instruments; AEM instruments never approached this much energy. CONCLUSIONS: Serious burn injury results from small amounts of energy leaked from standard instruments. AEM instruments appeared protective and did not leak sufficient energy to cause burn injuries to the bowel.

Programmable patterning of protein bioactivity by visible light.

The simple and quick patterning of functional proteins on engineered surfaces affords an opportunity to fabricate protein microarrays in lab-on-chip systems. We report on the programmable patterning of proteins as well as the local activation of enzymes by visible light. We successfully generated functional protein patterns with different geometries in situ and demonstrated the specific patterning of multiple kinds of proteins side-by-side without the need for specific linker molecules or elaborate surface preparation.

First-in-human evaluation of a hexon chimeric adenovirus vector expressing HIV-1 Env (IPCAVD 002).

BACKGROUND: We report the first-in-human safety and immunogenicity assessment of a prototype hexon chimeric adenovirus (Ad) serotype 5 (Ad5) vector containing the hexon hypervariable regions of Ad serotype 48 (Ad48) and expressing human immunodeficiency virus (HIV) type 1 EnvA. METHODS: Forty-eight Ad5 and Ad48 seronegative, HIV-uninfected subjects were enrolled in a randomized, double-blind, placebo-controlled, dose escalation phase 1 study. Four groups of 12 subjects received 10(9) to 10(11) viral particles (vp) of the Ad5HVR48.EnvA.01 vaccine (n = 10 per group) or placebo (n = 2 per group) at week 0 or weeks 0, 4, and 24. Safety and immunogenicity were assessed. RESULTS: Self-limited reactogenicity was observed after the initial immunization in the highest (10(11) vp) dose group. Responses in vaccinees included Ad48 neutralizing antibody (nAb) titers higher than Ad5 nAb titers, EnvA-specific enzyme-linked immunosorbent assay titers, and EnvA-specific enzyme-linked immunospot assay responses, and these responses generally persisted at week 52. At week 28 in the 10(9), 10(10), and 10(11) vp 3-dose groups, geometric mean EnvA enzyme-linked immunosorbent assay titers were 5721, 10 929, and 3420, respectively, and Ad48 nAb titers were a median of 1.7-fold higher than for Ad5. CONCLUSIONS: Ad5HVR48.ENVA.01 was safe, well tolerated, and immunogenic at all doses tested. Vector-elicited nAb responses were greater for Ad48 than Ad5, confirming that Ad-specific nAbs in humans are primarily, but not exclusively, directed against the hexon hypervariable regions. Clinical Trials Registration. NCT00695877.

First-in-human evaluation of the safety and immunogenicity of a recombinant adenovirus serotype 26 HIV-1 Env vaccine (IPCAVD 001).

BACKGROUND: We report the first-in-human safety and immunogenicity assessment of a prototype Ad26 vector-based human immunodeficiency virus (HIV) vaccine in humans. METHODS: Sixty Ad26-seronegative, healthy, HIV-uninfected subjects were enrolled in a randomized, double-blinded, placebo-controlled, dose-escalation phase 1 study. Five groups of 12 subjects received 10(9)-10(11) vp of the Ad26-EnvA vaccine (N = 10/group) or placebo (N = 2/group) at weeks 0 and 24 or weeks 0, 4, and 24. Safety and immunogenicity were assessed. RESULTS: Self-limited reactogenicity was observed after the initial immunization at the highest (10(11) vp) dose. No product-related SAEs were observed. All subjects who received the Ad26-EnvA vaccine developed Ad26 NAb titers, EnvA-specific enzyme-linked immunosorbent assays (ELISA) titers, and EnvA-specific enzyme-linked immunospot assays (ELISPOT) responses. These responses persisted at week 52. At week 28 in the 10(9), 10(10), 10(11) vp 3-dose and the 10(10) and 5 × 10(10) vp 2-dose groups, geometric mean EnvA ELISA titers were 6113, 12 470, 8545, 3470, and 9655 and mean EnvA ELISPOT responses were 397, 178, 736, 196, and 1311 SFC/10(6) peripheral blood mononuclear cells, respectively. CONCLUSION: This Ad26 vectored vaccine was generally safe and immunogenic at all doses tested. Reactogenicity was minimal with doses of 5 × 10(10) vp or less. Ad26 is a promising new vaccine vector for HIV-1. CLINICAL TRIALS REGISTRATION: NCT00618605.

Neuroinvasive Bacillus cereus Infection in Immunocompromised Hosts: Epidemiologic Investigation of 5 Patients With Acute Myeloid Leukemia.

Background: Bacillus cereus is a ubiquitous gram-positive rod-shaped bacterium that can cause sepsis and neuroinvasive disease in patients with acute leukemia or neutropenia. Methods: A single-center retrospective review was conducted to evaluate patients with acute leukemia, positive blood or cerebrospinal fluid test results for B cereus, and abnormal neuroradiographic findings between January 2018 and October 2022. Infection control practices were observed, environmental samples obtained, a dietary case-control study completed, and whole genome sequencing performed on environmental and clinical Bacillus isolates. Results: Five patients with B cereus neuroinvasive disease were identified. All patients had acute myeloid leukemia (AML), were receiving induction chemotherapy, and were neutropenic. Neurologic involvement included subarachnoid or intraparenchymal hemorrhage or brain abscess. All patients were treated with ciprofloxacin and survived with limited or no neurologic sequelae. B cereus was identified in 7 of 61 environmental samples and 1 of 19 dietary protein samples-these were unrelated to clinical isolates via sequencing. No point source was identified. Ciprofloxacin was added to the empiric antimicrobial regimen for patients with AML and prolonged or recurrent neutropenic fevers; no new cases were identified in the ensuing year. Conclusions: B cereus is ubiquitous in the hospital environment, at times leading to clusters with unrelated isolates. Fastidious infection control practices addressing a range of possible exposures are warranted, but their efficacy is unknown and they may not be sufficient to prevent all infections. Thus, including B cereus coverage in empiric regimens for patients with AML and persistent neutropenic fever may limit the morbidity of this pathogen.

Optimization of isopolar microtubule arrays.

Isopolar arrays of aligned cytoskeletal filaments are components in a number of designs of hybrid nanodevices incorporating biomolecular motors. For example, a combination of filament arrays and motor arrays can form an actuator or a molecular engine resembling an artificial muscle. Here, isopolar arrays of microtubules are fabricated by flow alignment, and their quality is characterized by their degree of alignment. We find, in agreement with our analytical models, that the degree of alignment is ultimately limited by thermal forces, while the kinetics of the alignment process are influenced by the flow strength, the microtubule stiffness, the gliding velocity, and the tip length. Strong flows remove microtubules from the surface and reduce the filament density, suggesting that there is an optimal flow strength for the fabrication of ordered arrays.

Facial tightening with an advanced 4-MHz monopolar radiofrequency device.

BACKGROUND: Over the past 10 years, radiofrequency (RF) technology has been utilized for nonablative treatments for the treatment of rhytides and skin laxity. This manuscript reviews the scientific background of collagen synthesis in vivo and in response to RF energy as well as a clinical study of 17 patients receiving a series of facial treatments with a 4-MHz monopolar RF (Pellevé, Ellman International, Inc, Oceanside, NY). Clinical methods, results, and a review of the literature for RF aesthetic treatments of the face are presented. METHODS: Seventeen patients were treated in one site with 6 total treatments scheduled as follows: 1 session was performed every 15 days for 2 consecutive sessions, 1 session every month for 2 consecutive sessions, and 1 session every 2 months for 2 consecutive sessions. Both the treating physician and the patients via live viewing and comparison with baseline photographs performed assessment of results. Results are reported as averages across the 17 patients. RESULTS: Two weeks after the first treatment, patients noted an overall average of 25% to 30% improvement. Just before the last or sixth treatment, there was an average of 50% improvement noted by the physician, with patients ranking an average self-improvement of 48%. The treating physician rated average improvement of 46% compared with baseline, whereas the patients ranked average improvement of 30% compared with baseline at 1 year after treatment was initiated (6 months after the final treatment). Patients find this treatment to be very well tolerated, with minimal to no discomfort and no downtime or significant side effects. CONCLUSIONS: The Pellevé 4-MHz monopolar RF device is effective, safe, and very well tolerated for treating laxity, texture, and wrinkles of the skin without complication or discomfort. Evidence in the literature supports the scientific mechanism of action of acute collagen modification and continued neocollagenesis observed with the system. In this cohort, patients maintain approximately 50% improvement on average at 6 months and a 30% to 50% improvement 1 year after beginning the treatments, 6 months after completion.