Extended stability of the trastuzumab biosimilar ABP 980 (KANJINTI™) in polyolefin bags and elastomeric devices

Study Objectives: To investigate the quality and in-use stability of the trastuzumab biosimilar ABP 980 (KANJINTI™) in both concentrated multi-dose bags and following dilution and extended storage in intravenous (IV) bags and elastomeric devices, to address the stability requirements of diff erent global pharmacy practices. Methods: The eff ect of extended refrigerated storage plus exposure to in-use temperature conditions on KANJINTI™ (trastuzumab) solutions was assessed using a range of stability-indicating analytical methods, including appearance, pH, SEC, nonreducing CGE, reducing-CGE, CZE, sub-visible particle counting and potency by a cell-based proliferation inhibition assay. Stability of reconstituted 21 mg/mL solution stored in multi-dose bags and diluted samples at 0.3 mg/mL, 0.8 mg/mL and 4 mg/ mL in 0.9% w/v NaCl solutions stored in IV bags and elastomeric devices was determined over diff erent storage durations. Forced degraded samples exposed to room temperature and natural daylight were used to demonstrate the stability-indicating abilities of the methods. Results: No signifi cant changes were observed in the appearance, pH, monomer concentration, purity, charge heterogeneity, sub-visible particle counts or bioactivity, regardless of initial concentration, container or storage duration. Discussion: There was no indication of signifi cant changes to the physicochemical stability or bioactivity of any of the solutions following extended storage when compared to the initial results acquired on the day of preparation. Conclusion: The data presented has demonstrated the physicochemical stability and bioactivity of a range of KANJINTI™ (trastuzumab) solutions when prepared using controlled and validated aseptic processes, stored protected from light for extended periods at 2°C–8°C and subjected to in-use temperatures. The stability demonstrated in multi-dose bags and elastomeric devices provides additional preparation options to address diff erent global pharmacy practices and requirements.

Influence of a Post-dam Sediment Pulse and Post-fire Debris Flows on Steelhead Spawning Gravel in the Carmel River, California

Spawning gravel scarcity is a limiting factor for successful recovery of federally-threatened anadromous fish like steelhead of central California. A BACI-experimental design using bed particle counts from 2013 through 2021 shows that spawning-sized gravel (32–90 mm) diminished downstream of the former San Clemente Dam site in 2017, following dam removal in 2015. High flows in 2017 transported a pulse of sand and fine-gravel that filled pools and runs throughout the river below the dam. The bed material in the 3 km closest to the dam remained too coarse for redds in riffles and too fine in pools and runs. Time-series bathymetric data of the Los Padres Dam reservoir located in the upper Carmel watershed shows that nearly all bed material (including spawning gravel) in the upper Carmel River watershed was recruited during wet winters that immediately followed expansive wildfires. We studied that effect in detail following the Carmel Fire of August 2020, which preconditioned the slopes adjacent to the Carmel River for debris flows. Our analysis of several fire-mediated debris flows in 2021 show that they contained virtually no mud and held approximately 45% spawning-sized gravel. Although the debris flows contained abundant spawning gravel, and several flow snouts terminated in the Carmel River, the material was dispersed downstream rather than forming bars and patches that could be used for steelhead nest building. The generally small volume of material in the flows relative to the size of the river channel and impediments to debris flow runout limited the contribution of spawning-size gravel to the river.

Visualization of Airborne Particles as a Risk for Microbial Contamination in Orthopedic Surgery

Background: The operating theater is recognized to involve a high frequency of occupational blood and body fluid contacts.Objectives: This study aimed to visualize the production of blood and body fluid airborne particles by surgical procedures and to investigate risks of microbial contamination of the conjunctival membranes of surgical staff during orthopedic operations.Methods: Two physicians simulated total knee arthroplasty (TKA) and total hip arthroplasty (THA) in a bio-clean theater using model bones. The generation and behaviors of airborne particles were filmed using a fine particle visualization system, and numbers of airborne particles per 2.83 L of air were counted at the height of the operating and instrument tables. Each action was repeated five times, and particle counts were evaluated statistically.Results: Numerous airborne particles were dispersed to higher and wider areas while “cutting bones in TKA” and “striking and driving the cup component on the pelvic bone in THA” compared to other surgical procedures. The highest particle counts were detected while “cutting bones in TKA” under unidirectional laminar air flow.Discussion: These results provide a clearer image of the dispersion and distribution of airborne particles and identified higher-risk surgical procedures for microbial contamination of the conjunctival membranes. Surgical staff including surgeons, nurses, anesthesiologists, and visitors, should pay attention to and take measures against occupational infection particularly in high-risk surgical situations.

Aerosolization of Mycobacterium tuberculosis by tidal breathing

Rationale: Interrupting tuberculosis (TB) transmission requires an improved understanding of how - and when - the causative organism, Mycobacterium tuberculosis (Mtb), is aerosolized. Although Cough is commonly assumed to be the dominant source of Mtb aerosols, recent evidence of Cough-independent Mtb release implies the contribution of alternative mechanisms. Objective: To compare the aerosolization of Mtb and particulate matter from GeneXpert-positive patients during three separate respiratory manoeuvres: Tidal Breathing (TiBr), Forced Vital Capacity (FVC), and Cough. Methodology: Bioaerosol sampling and Mtb detection were combined with real-time assessments of CO2 production and particle counts from 39 confirmed TB patients. Measurements and Main Results: TiBr and FVC produced comparable numbers of particles, with Cough producing >4-fold more. For all manoeuvres, the proportions of particles detected across size categories from 0.5 - 5 µm were similar, with minor differences observed only in particles between 1.5 - 2 µm (p = 0.014) and >5 µm (p = 0.020). Viable Mtb bacilli were detected in 66%, 70%, and 65% of TiBr, FVC, and Cough samples, respectively. Notably, while Cough produced 3-fold more Mtb than TiBr, the relative infrequency of coughing compared to breathing implies that TiBr likely contributes >90% of the daily aerosolised Mtb across a range of Cough frequencies. Conclusions: Our results suggest that, while Cough increases particle aerosolization compared to TiBr, this is not associated with increased Mtb aerosolization. Instead, TiBr produces more Mtb per particle than Cough. Assuming the number of viable Mtb organisms detected provides a proxy measure of patient infectiousness, these observations imply a significant contribution of TiBr to TB transmission.

The effect of increasing indoor ventilation on artificially generated aerosol particle counts

The COVID-19 global pandemic has caused millions of infections and deaths despite mitigation efforts that involve physical distancing, mask-wearing, avoiding indoor gatherings and increasing indoor ventilation. The purpose of this study was to compare ways to improve indoor ventilation and assess its effect on artificially generated aerosol counts. It was hypothesized that inbuilt kitchen vents would be more effective in reducing indoor aerosol counts than opening windows alone. A fixed amount of saline aerosol was dispersed in the experimental area using a nebulizer under constant temperature and a narrow range of humidity. A laser air quality monitor was used to record small particle counts every 30 minutes from baseline to 120 minutes for four different experimental groups for each combination of kitchen vents and windows. The results of the study demonstrate that aerosol counts were lowest with the kitchen exhaust vents on. This study suggests that liberal use of home exhaust systems like the kitchen vents could achieve significantly more air exchange than open windows alone and may present an effective solution to improving indoor ventilation, especially during the colder months when people tend to congregate indoors in closed spaces. There were no safety concerns involved when conducting this experiment.

Factors Affecting the Microstructure, Tensile Properties and Corrosion Resistance of AA7075 Forgings

AA7075 alloys are high strength alloys and are used as an important material for making engineering parts. Forged AA7075 alloys showed significantly decreased toughness when the material was hot deformed at a high temperature. This study investigated the effects of forging parameters on the tensile properties and the microstructure of AA7075 forgings. The tensile properties and corrosion resistance of different forgings were determined to be correlated with their microstructures. The experiment annealed and hot-deformed sample bars at 633 K, cold-deformed them at room temperature (RF), and at sub-zero temperatures (CF). After T73 heat treatment, the microstructures depended on the deformation temperature. This varied significantly, from elongated grains for hot-forged samples to equiaxial grains for cold-deformed samples. The hot-deformed samples had a tensile strength of 592 MPa for UTS, 538 MPa for YS, and 13.4% for elongation. These were stronger but less elongated than the cold-deformed samples. All hot-deformed (HF), RF, and CF samples exhibited mechanical properties that exceeded UTS > 505 MPa, YS > 435 MPa, and an elongation > 13%, and showed moderate corrosion resistance if samples were in contact with a 3.5 wt.% NaCl solution. The toughness of the forgings could be significantly improved by decreasing the forging temperatures. The corrosion resistance of AA7075-T73 forgings was affected by the total grain boundary (GB) lengths per unit area and the 2nd phase particle counts per unit area. Increasing the high-angle grain boundary lengths (HAGBs) per unit area accelerated corrosion and increased the Icorr value.

Clinical Efficacy of Novel Patient-Covering Negative-Pressure Box for Shielding Virus Transmission during Esophagogastroduodenoscopy: A Prospective Observational Study

Esophagogastroduodenoscopy (EGD) has a high risk of virus transmission during the current coronavirus disease 2019 era, and preventive measures are under investigation. We investigated the effectiveness of a newly developed patient-covering negative-pressure box system (Endo barrier®) (EB) for EGD. Eighty consecutive unsedated patients who underwent screening EGD with EB use were prospectively enrolled. To examine the aerosol ratio before, during, and after EGD, 0.3- and 0.5-μm aerosols were measured every 60 s using an optical counter. Moreover, the degree of contamination of the examiners’ goggles and vinyl gowns was assessed before and after EGD using a rapid adenosine triphosphate (ATP) test for simulated droplets. Data were available in 73 patients and showed that 0.3- and 0.5-μm particles did not increase in 95.8% (70/73) and 94.5% (69/73) of patients during EGD under EB. There were no significant differences in the total 0.3- or 0.5-μm particle counts before versus after EGD. The difference in the ATP levels before and after EGD was −0.6 ± 16.6 relative light units (RLU) on goggles and 1.59 ± 19.9 RLU on gowns (both within the cutoff value). EB use during EGD may provide a certain preventive effect against aerosols and droplets, decreasing examiners’ exposure to viruses.

Laboratory Study of Physical Barrier Efficiency for Worker Protection against SARS-CoV-2 while Standing or Sitting

Transparent barriers were installed as a response to the SARS-COV-2 pandemic in many customer-facing industries. Transparent barriers are an engineering control that are utilized to intercept air traveling between customers to workers. Information on the effectiveness of these barriers against aerosols is limited. In this study, a cough simulator was used to represent a cough from a customer. Two optical particle counters were used (one on each side of the barrier, labeled reference and worker) to determine the number of particles that migrated around a transparent barrier. Nine barrier sizes and a no barrier configuration were tested with six replicates each. Tests of these 10 configurations were conducted for both sitting and standing scenarios to represent configurations common to nail salons and grocery stores, respectively. Barrier efficiency was calculated using a ratio of the particle count results (reference/worker). Barriers had better efficiency when they were 9 to 39 cm (3.5 to 15.5 inches) above cough height and at least 91 cm (36 inches) wide, 92% and 93% respectively. Barriers that were 91 cm (36 inches) above table height for both scenarios blocked 71% or more of the particles between 0.35–0.725 µm and 68% for particles between 1 to 3 µm. A barrier that blocked an initial cough was effective at reducing particle counts. While the width of barriers was not as significant as height in determining barrier efficiency it was important that a barrier be placed where interactions between customers and workers are most frequent.

COVID-19 in the Clinic: Human Testing of an Aerosol Containment Mask for Endoscopic Clinic Procedures

Objective To create an aerosol containment mask (ACM) for common otolaryngologic endoscopic procedures that also provides nanoparticle-level protection to patients. Study Design Prospective feasibility study . Setting In-person testing with a novel ACM. Methods The mask was designed in Solidworks and 3D printed. Measurements were made on 10 healthy volunteers who wore the ACM while reading the Rainbow Passage repeatedly and performing a forced cough or sneeze at 5-second intervals over 1 minute with an endoscope in place. Results There was a large variation in the number of aerosol particles generated among the volunteers. Only the sneeze task showed a significant increase compared with normal breathing in the 0.3-µm particle size when compared with a 1-tailed t test ( P = .013). Both the 0.5-µm and 2.5-µm particle sizes showed significant increases for all tasks, while the 2 largest particle sizes, 5 and 10 µm, showed no significant increase (both P < .01). With the suction off, 3 of 30 events (2 sneeze events and 1 cough event) had increases in particle counts, both inside and outside the mask. With the suction on, 2 of 30 events had an increase in particle counts outside the mask without a corresponding increase in particle counts inside the mask. Therefore, these fluctuations in particle counts were determined to be due to random fluctuation in room particle levels. Conclusion ACM will accommodate rigid and flexible endoscopes plus instruments and may prevent the leakage of patient-generated aerosols, thus avoiding contamination of the room and protecting health care workers from airborne contagions. Level of evidence 2