The humidification process of medical gases plays a crucial role in both invasive and non-invasive ventilation, aiming to mitigate the complications arising from bronchial dryness. While passive humidification systems (HME) and active humidification systems are prevalent in routine clinical practice, there is a pressing need for further evaluation of their significance. Additionally, there is often an incomplete understanding of the operational mechanisms of these devices. The current review explores the historical evolution of gas conditioning in clinical practice, from early prototypes to contemporary active and passive humidification systems. It also discusses the physiological principles underlying humidity regulation and provides practical guidance for optimizing humidification parameters in both invasive and non-invasive ventilation modalities. The aim of this review is to elucidate the intricate interplay between temperature, humidity, and patient comfort, emphasizing the importance of individualized approaches to gas conditioning.

Ocular inserts offer distinct advantages, including a preservative-free drug delivery system, the ability to provide tailored drug release, and ease of administration. The present research paper delves into the development of an innovative ocular insert using CaliCut technology. Complementing the hot melt extrusion (HME) process, CaliCut, an advanced technology in ocular insert development, employs precision laser gauging to achieve impeccable cutting of inserts with desired dimensions. Its intelligent control over the stretching process through auto feedback-based belt speed adjustment ensures unparalleled accuracy and consistency in dosage form manufacturing. Dry eye disease (DED) poses a significant challenge to ocular health, necessitating innovative approaches to alleviate its symptoms. In this pursuit, castor oil has emerged as a promising therapeutic agent, offering beneficial effects by increasing the thickness of the lipid layer in the tear film, thus improving tear film stability, and reducing tear evaporation. To harness these advantages, this study focuses on the development and comprehensive characterization of castor oil-based ocular inserts. Additionally, in-vivo irritancy evaluation in rabbits has been undertaken to assess the inserts\' safety and biocompatibility. By harnessing the HME and CaliCut techniques in the formulation process, the study demonstrates their instrumental role in facilitating the successful development of ocular inserts.

Extracellular vesicles (EVs) play an important role in human and bovine milk composition. According to excellent published studies, it also exerts various functions in the gut, bone, or immune system. However, the effects of milk-derived EVs on skeletal muscle growth and performance have yet to be fully explored. Firstly, the current study examined the amino acids profile in human milk EVs (HME) and bovine milk EVs (BME) using targeted metabolomics. Secondly, HME and BME were injected in the quadriceps of mice for four weeks (1 time/3 days). Then, related muscle performance, muscle growth markers/pathways, and amino acids profile were detected or measured by grip strength analysis, rotarod performance testing, Jenner-Giemsa/H&E staining, Western blotting, and targeted metabolomics, respectively. Finally, HME and BME were co-cultured with C2C12 cells to detect the above-related indexes and further testify relative phenomena. Our findings mainly demonstrated that HME and BME significantly increase the diameter of C2C12 myotubes. HME treatment demonstrates higher exercise performance and muscle fiber densities than BME treatment. Besides, after KEGG and correlation analyses with biological function after HME and BME treatment, results showed L-Ornithine acts as a \"notable marker\" after HME treatment to affect mouse skeletal muscle growth or functions. Otherwise, L-Ornithine also significantly positively correlates with the activation of the AKT/mTOR pathway and myogenic regulatory factors (MRFs) and can also be observed in muscle and C2C12 cells after HME treatment. Overall, our study not only provides a novel result for the amino acid composition of HME and BME, but the current study also indicates the advantage of human milk on skeletal muscle growth and performance.

BACKGROUND: In patients after total laryngectomies, the trachea and the lung can be easily infected by SARS-CoV-2 because the respiration happens through the tracheostoma.
OBJECTIVE: The aim of our study was to examine whether patients with LaryTube™ can distribute aerosols to a greater extent than without LaryTube™, and to observe whether the surface of different protective instruments can be examined using the thermal camera in total laryngectomees. An important objective was also to confirm the assumption that the use of HME (heat and moisture exchanger) alone does not provide protection during COVID-19 pandemic. Finally, during our tests, we tried to get an answer to our assumption that the sample taken from the inner surface of the HME can be tested for SARS-CoV-2.
METHODS: A total of 23 patients who underwent total laryngectomies were analyzed by velocity measurements and thermal imaging with and without HMEs and laryngeal tubes, using different types of PPEs. COVID-19 PCR testing was performed on patient tracheas and the inner surfaces of the HMEs.
RESULTS: Male patients with laryngeal tubes without HMEs demonstrated an increase in exhaled airflow velocity of more than 43% compared to male patients without laryngeal tubes; in female patients, the same value was more than 39%. Thermal imaging results confirmed that the lowest surface temperature was measured on FFP2 masks. The sent samples can be tested for SARS-CoV-2 using PCR, the presence of the virus was not detected.
CONCLUSIONS: Laryngectomized patients without laryngeal tubes pose a lower risk for spreading viral aerosols due to the reduced velocity of the exhaled airflow caused by the absence of the tube as the narrowing factor. Patients with laryngeal tubes who undergo total laryngectomies during the COVID-19 pandemic should use HMEs with viral filter, if possible, also changing the laryngeal tubes to dermal adhesives for fitting their HMEs seems to be the best option. The surface of the used protective equipment can also be examined with thermal camera in the case of total laryngectomees. COVID-19 PCR testing of the tracheal secretion from the inner HME surfaces should become a routine in clinical practice if deemed necessary. Orv Hetil. 2023; 164(34): 1327-1336.
Bevezetés: A teljes gégeeltávolításon átesett betegeknél a légcső és a tüdő a SARS-CoV-2 közvetlen fertőzésének további helyeként szolgálhat, mivel a légúti áramlás a tracheostomán keresztül történik. Célkitűzés: Tanulmányunk célja volt, hogy megvizsgáljuk, LaryTube™ mellett a betegek képesek-e nagyobb mértékben aeroszolok terjesztésére, mint LaryTube™ nélkül, továbbá az, hogy megfigyeljük, vizsgálható-e különböző védőeszközök felszíne a hőkamera segítségével ebben a betegcsoportban. Fontos célkitűzésként szerepelt az is, hogy megerősítsük a feltételezést, miszerint a HME (heat and moisture exchanger – hő- és nedvességcserélő) használata önmagában nem nyújt védelmet COVID–19-pandémia esetén. Végül vizsgálataink során próbáltunk választ kapni arra a feltételezésünkre, hogy a HME belfelszínéről vett minta tesztelhető-e SARS-CoV-2 irányában. Módszer: Teljes gégeeltávolításon átesett 23 beteg kilélegzett levegőjének sebességét mértük HME-vel és HME nélkül, LaryTube™ használatával, illetve anélkül. Az általunk kiválasztott védőeszközök felszínén hőkamerás vizsgálatot végeztünk, melyeket minden esetben a beteg stomája elé helyeztünk. A HME belfelszínéről és a trachea hátsó faláról vett váladékot az esetleges SARS-CoV-2-pozitivitás miatt PCR-vizsgálatnak vetettük alá. Eredmények: LaryTube™-bal ellátott férfi betegeink HME nélkül 43%-kal gyorsabban fújták ki levegőjüket, mint a LaryTube™ nélküliek. Nők esetében ez az érték 39% fölött volt. A legalacsonyabb felszíni hőmérsékletet az FFP2-es maszk esetében regisztráltuk. A küldött minták PCR segítségével SARS-CoV-2-re tesztelhetők, vírus jelenlétét nem mutatták ki. Következtetés: A teljes gégeeltávolításon átesett betegek LaryTube™ nélkül kisebb eséllyel képesek az aeroszolok terjesztésére, mivel hiányzik a tubus mint a stoma szűkítő tényezője. Ezen betegeknek ajánlott COVID–19-pandémia idején a vírusszűrővel ellátott HME használata, sőt a legracionálisabb megoldás a tubus elhagyása és tapaszra cserélése a HME rögzítése miatt. A használt védőeszközök felszíne hőkamerával vizsgálható laryngectomián átesett betegek esetében is. Szükség esetén bevezethető a klinikai gyakorlatba a HME belfelszínéről vett minta PCR-tesztelése SARS-CoV-2 irányában, mely sokkal biztonságosabb módszernek bizonyult. Orv Hetil. 2023; 164(34): 1327–1336.

Heat and moisture exchangers (HMEs) are commonly used during general anesthesia to provide appropriate humidification and warming of inspired gases. While they play a critical role in mechanical ventilation, they can also lead to acute difficult ventilation if not correctly monitored and drained. We present a case of a 56-year-old female patient who underwent lower extremity vascular bypass surgery under general anesthesia and experienced sudden increased airway pressures due to occlusion of the HME caused by excessive moisture accumulation. Proper monitoring and management of the airway circuit and HMEs can help prevent complications and ensure proper ventilation during surgery. When acute difficult ventilation is encountered during general anesthesia, a systematic approach should be taken to differentiate between patient and external factors. Other differential diagnoses for acute difficult ventilation include bronchospasm, aspiration, endotracheal tube misplacement, pulmonary embolism, and tension pneumothorax. HME occlusion should be considered as part of the differential diagnosis for intraoperative hypoxia. Proactive replacement of HMEs in long cases can prevent occlusion and ensure proper ventilation.

To improve the understanding of the thermodynamics and performance of small passive hygroscopic Heat and Moisture Exchangers (HMEs), a computer model simulating HME function is required.
We developed a numerical HME model to calculate the HME\'s water and heat exchange. The model was tuned and verified with experimental data and validated by applying it to HME design variations.
Verification of the model\'s results to the experimental data shows that the tuned model yields reliable results. The mass of the core, which determines the HME\'s total heat capacity, is the most important parameter influencing the performance of passive HMEs.
Increasing the HME\'s diameter is an effective way to improve an HME, as it yields higher performance and lowers breathing resistance. HMEs intended for use in warm or dry climates should contain more and those for use in cold humid climates should contain less hygroscopic salt.

BACKGROUND: Notwithstanding the benefits of heat and moisture exchangers (HMEs) in both clinical research and practice, a gap exists between the optimal physiological humidification created through the nasal function and the humidification capacity of HMEs for patients after total laryngectomy. In this study, 5 new HMEs (Provox Life) specialized for situational use with improved humidification capacities were evaluated.
OBJECTIVE: This study aims to evaluate the effectiveness of the existing HMEs, assess the potential effectiveness of the new HMEs, and elicit expert judgments on the new HMEs\' expected effectiveness and impact on health care use.
METHODS: First, a rapid literature review (RLR) was performed to identify evidence on the clinical outcomes, health outcomes, and complications of HMEs in patients who underwent laryngectomy. Second, semistructured interviews with German experts (n=4) were conducted to validate the findings of the RLR and identify reasonable expectations regarding the potential of the new HMEs. Third, a structured expert elicitation among German experts (n=19) was used to generate quantitative evidence on the expected effectiveness of the new HMEs in clinical and health outcomes.
RESULTS: The RLR (n=10) demonstrated that HME use by patients has advantages compared with no HME use concerning breathing resistance, tracheal dryness and irritation, mucus production and plugging, frequency of cough and forced expectorations, sleep quality, voice quality, use of physiotherapy, tracheobronchitis or pneumonia episodes, quality of life, and patient satisfaction. From the expert interviews and structured expert elicitation, it was found that, on average, experts expect that compared with the second-generation HMEs, the new HMEs will lead to a decrease in tracheal dryness or irritation (51%, SD 24%, of patients), mucus plug events (33%, SD 32%, of patients), mucus production (53%, SD 22%, of patients), physiotherapy (0.74, SD 0.70, days) and pulmonary infections (34%, SD 32%) and an increase or improvement in speech quality (25%, SD 23%, of patients), social contacts (13%, SD 18%), quality of life (33%, SD 30%), and patient satisfaction (44%, SD 30%). An improvement in breathing (53%, SD 28%, of patients) and shortness of breath (48%, SD 25%, of patients) was expected. The average number of daily cough periods and forced expectorations was expected to be 2.95 (SD 1.61) and 2.46 (SD 1.42), respectively. Experts expect that, on average, less than half of the patients will experience sleeping problems (48%, SD 22%) and psychosocial problems (24%, SD 20%).
CONCLUSIONS: According to German experts, it is expected that the new HMEs with improved humidification levels will lead to additional (clinical) effectiveness on pulmonary health and an improved overall quality of life of patients compared with the currently available HMEs.

Hot melt extrusion (HME) has been used for the formulation of topical solid lipid nanoparticle (SLN) gel without using any other size reduction technique including high pressure homogenization or sonication. SLN formulation solely using HME has not been applied to other drugs except IBU. Therefore, the purpose of the present study was to formulate FLB SLN solely using HME technique and evaluate the SLN formulation in inflammation animal model. Stable 0.5% w/v FLB SLN gel with particle size < 250 nm, PI < 0.3 and EE of > 98% was prepared. Differential scanning calorimetry (DSC) thermogram showed that the drug was converted to amorphous form in the HME process. Additionally, rheological studies demonstrated that FLB SLN gel and marketed FLB gel showed shear thinning property. FLB SLN formulation showed significantly (p < 0.05) higher peak force required to spread the formulation as compared to marketed FLB formulation. Stability studies showed that FLB SLN gel was stable for a month at room temperature and 2-4°C. Moreover, in vitro permeation test (IVPT) and ex vivo skin deposition study results revealed that FLB SLN gel showed significant (p < 0.05) increase in drug deposition in dermal layer and drug permeation as compared to control marketed formulation. Further, in vivo anti-inflammatory study showed equivalent inhibition of rat paw edema using 0.5% w/v FLB SLN gel which has 10 times less strength compared to control formulation. Overall, FLB SLN formulation was successfully manufactured solely using HME technique which resulted in enhanced the skin permeation of FLB and superior anti-inflammatory activity.

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The combination of lopinavir/ritonavir remains one of the first-line therapies for the initial antiretroviral regimen in pediatric HIV-infected children. However, the implementation of this recommendation has faced many challenges due to cold-chain requirements, high alcohol content, and unpalatability for ritonavir-boosted lopinavir syrup. In addition, the administration of crushed tablets has shown a detriment for the oral bioavailability of both drugs. Therefore, there is a clinical need to develop safer and better formulations adapted to children\'s needs. This work has demonstrated, for the first time, the feasibility of using direct powder extrusion 3D printing to manufacture personalized pediatric HIV dosage forms based on 6 mm spherical tablets. H-bonding between drugs and excipients (hydroxypropyl methylcellulose and polyethylene glycol) resulted in the formation of amorphous solid dispersions with a zero-order sustained release profile, opposite to the commercially available formulation Kaletra, which exhibited marked drug precipitation at the intestinal pH.