Morphological features of the photoplethysmographic signal: a new approach to characterize the microcirculatory response to photobiomodulation.

Introduction and Objectives: Advanced analysis of the morphological features of the photoplethysmographic (PPG) waveform may provide greater understanding of mechanisms of action of photobiomodulation (PBM). Photobiomodulation is a non-ionizing, red to near-infrared irradiation shown to induce peripheral vasodilatation, promote wound healing, and reduce pain. Using laser Doppler flowmetry combined with thermal imaging we found previously in a clinical study that PBM stimulates microcirculatory blood flow and that baseline palm skin temperature determines, at least in part, why some individuals respond favorably to PBM while others do not. "Responders" (n = 12) had a skin temperature range of 33°C-37.5°C, while "non-responders" (n = 8) had "cold" or "hot" skin temperature (<33°C or >37.5°C respectively). The continuous PPG signals recorded from the index fingers of both hands in the original clinical study were subjected to advanced post-acquisitional analysis in the current study, aiming to identify morphological features that may improve the accuracy of discrimination between potential responders and non-responders to PBM. Methods: The PPG signals were detrended by subtracting the lower envelope from the raw signal. The Root Mean Square (RMS) and Entropy features were extracted as were two additional morphological features -- Smoothness and number of local extrema per PPG beat (#Extrema). These describe the signal jaggedness and were developed specifically for this study. The Wilcoxon test was used for paired comparisons. Correlations were determined by the Spearman correlation test (rs). Results: The PPG waveforms of responders to PBM had increased amplitude and decreased jaggedness (Baseline vs. 10' post-irradiation: Entropy, 5.0 ± 1.3 vs. 3.9 ± 1.1, p = 0.012; #Extrema, 4.0 ± 1.1 vs. 3.0 ± 1.6, p = 0.009; RMS, 1.6 ± 0.9 vs. 2.3 ± 1.2, p = 0.004; Smoothness, 0.10 ± 0.05 vs. 0.19 ± 0.16, p = 0.016). In addition, unilateral irradiation resulted in a bilateral response, although the response of the contralateral, non-irradiated hand was shorter in duration and lower in magnitude. Although subjects with 'cold,' or 'hot,' baseline skin temperature appeared to have morphologically distinct PPG waveforms, representing vasoconstriction and vasodilatation, these were not affected by PBM irradiation. Conclusion: This pilot study indicates that post-acquisitional analysis of morphological features of the PPG waveform provides new measures for the exploration of microcirculation responsiveness to PBM.

Perforated Concave Earplug (pCEP): A Proof-of-Concept Earplug to Improve Sound Localization without Compromising Noise Attenuation.

Combat soldiers are currently faced with using a hearing-protection device (HPD) at the cost of adequately detecting critical signals impacting mission success. The current study tested the performance of the Perforated-Concave-Earplug (pCEP), a proof-of-concept passive HPD consisting of a concave bowl-like rigid structure attached to a commercial roll-down earplug, designed to improve sound localization with minimal compromising of noise attenuation. Primarily intended for combat/military training settings, our aim was an evaluation of localization of relevant sound sources (single/multiple gunfire, continuous noise, spoken word) compared to 3M™-Combat-Arms™4.1 earplugs in open-mode and 3M™-E-A-R™-Classic™ earplugs. Ninety normal-hearing participants, aged 20-35 years, were asked to localize stimuli delivered from monitors evenly distributed around them in no-HPD and with-HPD conditions. The results showed (1) localization abilities worsened using HPDs; (2) the spoken word was localized less accurately than other stimuli; (3) mean root mean square errors (RMSEs) were largest for stimuli emanating from rear monitors; and (4) localization abilities corresponded to HPD attenuation levels (largest attenuation and mean RMSE: 3M™-E-A-R™-Classic™; smallest attenuation and mean RMSE: 3M™-Combat-Arms™4.1; pCEP was mid-range on both). These findings suggest that the pCEP may benefit in military settings by providing improved sound localization relative to 3M™ E-A-R™-Classic™ and higher attenuation relative to 3M™-Combat Arms™-4.1, recommending its use in noisy environments.

Natural history of changes in knee skin temperature following total knee arthroplasty: a systematic review and meta-analysis.

Patients undergoing total-knee arthroplasty (TKA) have transient increases in anterior knee skin temperature (ST) that subside as recovery progresses-except in cases of systemic or local prosthetic joint infections (PJI). This meta-analysis was designed to quantify the changes in knee ST following TKA in patients with uncomplicated recovery as a prerequisite for assessing the usefulness of thermal imaging for diagnosis of PJI. This meta-analysis (PROSPERO-CRD42021269864) was performed according to PRISMA guidelines. PUBMED and EMBASE were searched for studies reporting knee ST of patients that underwent unilateral TKA with uncomplicated recovery. The primary outcome was the weighted means of the differences in ST between the operated and the non-operated knees (ΔST) for each time point (before TKA, and 1 day; 1,2, and 6 weeks; and 3,6, and 12-months post-TKA). For this analysis, 318 patients were included from 10 studies. The elevation in ST was greatest during the first 2-weeks (ΔST = 2.8 °C) and remained higher than pre-surgery levels at 4-6 weeks. At 3-months, ΔST was 1.4 °C. It decreased to 0.9 °C and 0.6 °C at 6 and 12-months respectively. Establishing the baseline profile of knee ST following TKA provides the necessary first step for evaluating the usefulness of thermography for the diagnosis of post-procedural PJI.

Pre-intubation ventilation device for bearded patients: prospective, randomized, crossover trial in anesthetized patients.

Having a beard is an independent predictor of difficult ventilation by face mask. This study evaluates the efficacy of a novel intra-oral Bag-Valve-Guedel Adaptor (BVGA) in anaesthetized bearded patients. Patients with ASA score 1-2, scheduled for elective surgery, were recruited for this prospective, crossover trial. Beard length was categorized as < 0.5 cm, 0.5-1 cm, 1-5 cm, or > 5 cm. Patients were ventilated by attending anesthesiologists using the BVGA and a facemask (both with a Guedel oral airway). End-tidal CO2 (EtCO2) and expiratory tidal volume (TV) were recorded as was the number of hands required for the procedure. The primary outcome was the difference between BVGA and Facemask. Sixty-one patients were enrolled. Of these, 38 had beards, and 23 were without beards or with beards < 0.5 cm length. In bearded patients, ventilation with the BVGA was superior to the face mask by EtCO2 and non-inferior by TV (BVGA-vs-Mask, mean [95% CI]: EtCO2 [mmHg], 33.0 [31.6, 34.3]-vs-27.2 [25.5, 28.8], p < 0.001; TV [ml∙kg-1 IBW], 8.1 [7.4, 8.9]-vs-6.9 [6.0, 7.7], p = 0.11). The BVGA was found to be superior to the face mask by EtCO2 across all beard lengths (p ≤ 0.001), but by TV only for the longest beard group (p = 0.009). After securing the BVGA, ventilation was possible without hands in 74% of the cases - clearly impossible with the facemask (p ≤ 0.001). The BVGA is more effective and more convenient than the facemask in anaesthetized bearded patients. A follow-up study is underway to test whether replacing the face mask with the BVGA will improve effectiveness and ease of pre-intubation field ventilation by less-experienced, first responders.

Photobiomodulation as an Adjunctive Treatment to Physiotherapy for Reduction of Anterior Knee Pain in Combat Soldiers: A Prospective, Double-Blind, Randomized, Pragmatic, Sham-Controlled Trial.

BACKGROUND AND OBJECTIVES: Anterior knee pain (AKP) is the most common knee pathology in athletes and occurs in 15% of army recruits of elite units during basic training. Of these, 50% are symptomatic 6 years later. Photobiomodulation (PBM) is a nonthermal red-to-near-infrared irradiation used for pain reduction of a variety of etiologies. This study was designed to determine whether addition of PBM to physiotherapy (PT) for AKP in combat soldiers is superior to PT alone. STUDY DESIGN/MATERIALS AND METHODS: In this prospective, double-blind, sham-controlled, randomized clinical trial (NCT02845869), 26 combat soldiers/policemen (male:female, 15:11; body mass index [BMI] = 24.2 ± 3.9, n = 46 knees), with AKP due to overuse/load, received 4 weeks of PT + sham (PT + Sham) or active PBM (wavelength = 660 and 850 nm, pulsing = 2.5 Hz, LED power = 50 mW/cm2 [local tissue/regional lymph nodes]; 810 nm continuous beam, laser cluster 6 W/cm2 [analgesia] and laser pointer 4.75 W/cm2 [trigger points]) (PT + PBM). The main outcome measures were subjective pain by visual analog scale (VAS) (0 [none]-100 [intolerable]) and functional disability by Kujala score (0 [worst]-100 [best]). Evaluations were carried out at baseline, end of treatments, and 3-month follow-up. RESULTS: All participants completed the treatment protocol without any reported adverse device effects. Post-treatment pain was significantly reduced in the PT+PBM group, compared with baseline and sham (Δpain, VAS, mean ± SD: PT + PBM = -19 ± 23, P = 0.002; PT + Sham = -6 ± 21, P = 0.16; between groups, P = 0.032). At 3-month follow-up, pain reduction was similar between groups; however, the Kujala score was significantly improved only in the PBM-treated group (ΔKujala: PT + PBM = 11 ± 10, P = 0.003; PT + Sham = 5 ± 7, P = 0.059). CONCLUSIONS: Addition of PBM to PT for AKP resulted in earlier reduction in pain and improved functionality, compared with PT alone. This noninvasive, nonpharmacologic, adjunctive therapeutic modality can be easily incorporated into team healthcare frameworks or end units and may lead to earlier return to competition or combat-level service. Lasers Surg. Med. © 2021 Wiley Periodicals LLC.

Remote ischemic preconditioning improves tissue oxygenation in a porcine model of controlled hemorrhage without fluid resuscitation.

Remote ischemic preconditioning (RIPC) involves deliberate, brief interruptions of blood flow to increase the tolerance of distant critical organs to ischemia. This study tests the effects of limb RIPC in a porcine model of controlled hemorrhage without replacement therapy simulating an extreme field situation of delayed evacuation to definitive care. Twenty-eight pigs (47 ± 6 kg) were assigned to: (1) control, no procedure (n = 7); (2) HS = hemorrhagic shock (n = 13); and (3) RIPC + HS = remote ischemic preconditioning followed by hemorrhage (n = 8). The animals were observed for 7 h after bleeding without fluid replacement. Survival rate between animals of the RIPC + HS group and those of the HS group were similar (HS, 6 of 13[46%]-vs-RIPC + HS, 4 of 8[50%], p = 0.86 by Chi-square). Animals of the RIPC + HS group had faster recovery of mean arterial pressure and developed higher heart rates without complications. They also had less decrease in pH and bicarbonate, and the increase in lactate began later. Global oxygen delivery was higher, and tissue oxygen extraction ratio lower, in RIPC + HS animals. These improvements after RIPC in hemodynamic and metabolic status provide essential substrates for improved cellular response after hemorrhage and reduction of the likelihood of potentially catastrophic consequences of the accompanying ischemia.

Novel self-fixation chest drain device tested in a swine model of pneumo-hemothorax.

INTRODUCTION: Thoracic injuries account for 20-25% of trauma-related deaths. In cases of pneumothorax the insertion of a chest tube is mandatory but associated with high complication rates particularly when inserted under difficult conditions. The C-Lant is a novel chest-tube insertion device that provides integrated double fixation capabilities and can be used by responders with minimal experience. The aim of the study was to test the device in a large animal model. MATERIAL AND METHODS: Pneumothorax, tension pneumothorax, and hemothorax were induced in four white domestic female pigs. The C-Lant device (Vigor Medical Technologies, Haifa, Israel) was inserted as any chest-drain to decompress the thorax. Pull test was applied to test the strength of device fixation. RESULTS: The insertion of the device was simple and effective without detectable negative physiological effects. Reliable fixation was achieved without difficulty. Air and liquid were promptly drained from the chest cavity. Minimal tissue laceration occurred when applying the device in a scenario of erroneous pneumothorax diagnosis with fully expanded lungs. Interconnection with other surgical accessories was smooth. CONCLUSION: The C-Lant is a novel device that facilitates easy insertion and fixation of chest-tubes by minimally experienced medical providers and reduces the likelihood of unwanted expulsion. Clinical studies are planned.

Photobiomodulation and estrogen stabilize mitochondrial membrane potential in angiotensin-II challenged porcine aortic smooth muscle cells.

Rupture of Abdominal aortic aneurysm (AAA) is among the 15 leading causes of death after age 65. Using high frequency ultrasound, we showed that photobiomodulation (PBM) prevents formation and progression of AAA in the angiotensin-II (Ang-II)-infused, apolipoprotein-e-deficient mouse model. In the current study we report that while challenge of porcine aortic Smooth Muscle Cells (SMCs) with Ang-II (1 µM) resulted in a marked decay in mitochondrial membrane potential (MitMP) vs non-challenged cells, treatment with PBM (continuous diode laser, 780 nm, 6.7 mW/cm2 , 5 minutes, 2 J/cm2 ) or pre-incubation with estrogen (50 nM, 1 hour) significantly attenuated this deterioration in MitMP. We also report that PBM and estrogen markedly affected porcine aortic SMC contraction and modified mitochondrial dispersion reflecting important influence on SMC function. These studies provide strong evidence of the important underlying role of mitochondria in the preventive effect of PBM on formation and progression of AAA and its reduced incidence and delayed onset in women.

Wireless, non-invasive, wearable device for continuous remote monitoring of hemodynamic parameters in a swine model of controlled hemorrhagic shock.

Accurate and continuous monitoring of critically ill patients is frequently achieved using invasive catheters, which is technically complex. Our purpose was to evaluate the validity and accuracy of a photoplethysmography (PPG)-based remote monitoring device compared to invasive methods of arterial line (AL) and Swan-Ganz (SG) catheters in a swine model of controlled hemorrhagic shock. Following a baseline phase, hemorrhagic shock was induced in 11 pigs by bleeding 35% of their blood volume, followed by a post-bleeding follow-up phase. Animals were monitored concomitantly by the PPG device, an AL and a SG catheter, for a median period of 447 min. Heart rate (HR), systolic and diastolic blood pressure (SBP and DBP, respectively), and cardiac output (CO) were recorded continuously. The complete data set consisted of 1312 paired observations. Correlations between the PPG-based technique and the invasive methods were significant (p < 0.001) during baseline, bleeding and follow-up phases for HR (r = 0.90-0.98), SBP (r = 0.90-0.94), DBP (r = 0.89-0.93), and CO (r = 0.76-0.90). Intraclass correlations for all phases combined were 0.96, 0.92, 0.93 and 0.87 for HR, SBP, DBP and CO, respectively. Correlations for changes in CO, SBP and DBP were significant (p < 0.001) and strong (r > 0.88), with concordance rates (determined by quadrant plots) of 86%, 66% and 68%, respectively. The novel PPG-based device was accurate and valid compared to existing invasive techniques and might be used for continuous monitoring in several clinical settings following further studies.

Assessment of the Efficacy and Safety of a Novel, Low-Cost, Junctional Tourniquet in a Porcine Model of Hemorrhagic Shock.

INTRODUCTION: Commercially available junctional tourniquets (JTQs) have several drawbacks. We developed a low-cost, compact, easy to apply JTQ. The aim of this study was to assess the tourniquets' safety and efficacy in a swine model of controlled hemorrhage. MATERIALS AND METHODS: Five pigs were subjected to controlled bleeding of 35% of their blood volume. Subsequently, the JTQ was applied to the inguinal area for 180 minutes. Afterwards, the tourniquet was removed for additional 60 minutes of follow up. During the study, blood flow to both hind limbs and blood samples for tissue damage markers were repeatedly assessed. Following sacrifice, injury to both inguinal areas was evaluated microscopically and macroscopically. RESULTS: Angiography demonstrated complete occlusion of femoral artery flow, which was restored following removal of the tourniquet. No gross signs of tissue damage were noticed. Histological analysis revealed mild necrosis and infiltration of inflammatory cells. Blood tests showed a mild increase in potassium and lactic acid levels throughout the protocol. CONCLUSIONS: The tourniquet achieved effective arterial occlusion with minimal tissue damage, similar to reports of other JTQs. Subjected to further human trials, the tourniquet might be a suitable candidate for widespread frontline deployment because of its versatility, compactness, and affordable design.

Microcirculatory Response to Photobiomodulation-Why Some Respond and Others Do Not: A Randomized Controlled Study.

BACKGROUND AND OBJECTIVES: Photobiomodulation (PBM), a non-ionizing, non-thermal irradiation, used clinically to accelerate wound healing and inhibit pain, was previously shown to increase blood flow. However, some individuals respond to PBM, but others do not. The purpose of this study was to investigate factors affecting this patient-specific response using advanced, noninvasive methods for monitoring microcirculatory activity. STUDY DESIGN/MATERIALS AND METHODS: In this prospective, randomized controlled clinical trial (NCT03357523), 20 healthy non-smoking volunteers (10:10 males:females, 30 ± 8 years old) were randomized to receive either red- (633 nm and 70 W/cm2 ) or near-infrared light (830 nm and 55 mW/cm2 ) over the wrist for 5 minutes. Photoplethysmography, laser Doppler flowmetry, and thermal imaging were used to monitor palm microcirculatory blood volume, blood flow, and skin temperature, respectively, before, during, and 20 minutes after irradiation. Participants with skin temperature change ≥0.5°C from baseline were considered "responders". RESULTS: Near-infrared PBM was found to induce a 27% increase in microcirculatory flow that increased to 54% during the 20-minute follow-up period (P = 0.049 and P = 0.004, respectively), but red light PBM did not increase the median flow. Only 10 of 20 participants were responders by thermal imaging (i.e., ≥0.5°C from baseline), and their initial skin temperature was between 33 and 37.5°C. The non-responders had either "hot" hands (≥37.5°C) or "cold" hands (≤33°C). In responders, the meantime to 20% increase in microcirculatory blood volume and blood flow was less than 2.5 minutes after initiation of PBM irradiation. CONCLUSIONS: We demonstrated that PBM induces arteriolar vasodilatation that results in both immediate and long-lasting increased capillary flow and tissue perfusion in healthy individuals. This response was wavelength-dependent and modified by skin temperature. These findings regarding physiological parameters associated with sensitivity or resistance to PBM provide information of direct relevance for patient-specific therapy. Lasers Surg. Med. © 2020 Wiley Periodicals, Inc.

Ventilating the Bearded: A Randomized Crossover Trial Comparing a Novel Bag-Valve-Guedel Adaptor to a Standard Mask.

INTRODUCTION: Emergency field ventilation using bag-valve face mask devices can be difficult to perform, especially in bearded individuals. In view of the increasing numbers of servicemen and civilians sporting a beard or moustache, the issue of finding a technical solution for ventilation in this population has gained importance. We therefore developed a novel adaptor that enables the direct connection of a bag-valve device to a Guedel-type oropharyngeal airway device thereby directly connecting the oral airway to the bag valve, eliminating the need for a face mask. The objective of this study was to compare the efficacy of the bag-valve-Guedel adaptor (BVGA) to the common face mask in healthy bearded volunteers. METHODS: This study was a randomized-by-sequence, crossover-controlled trial (NCT02768246) approved by the local IRB (0051-16-HMO). All subjects signed an informed consent before participation. Twenty-five healthy bearded men (age 28 ± 7) were recruited. After randomization, the first group (mask then BVGA, n = 12) began breathing room air through the face mask, followed by 100% O2. After washout in room air, the procedure was repeated with the BVGA. The second group (BVGA then mask, n = 13) began with the BVGA followed by the face mask. Subjects were awake and breathed spontaneously throughout the experiment. Therefore, a Guedel was not used. Physiological and respiratory parameters were monitored continuously. The primary endpoint was the presence of suspected leak as determined by end-tidal-CO2 (EtCO2 < 20 mmHg). Secondary endpoints included tidal volume and safety. RESULTS: The order of device use did not affect the results significantly (p > 0.05 by Mann-Whitney-U test); therefore, the data were pooled. There were no cases of suspected leak while breathing through the BVGA. By contrast, while breathing through a face mask, there were 8 of 25 (32%) and 5 of 25 (20%) cases of suspected leak in air and 100% O2, respectively (air: p = 0.002; 100% O2: p = 0.014 by McNemar test). No adverse events were observed. CONCLUSIONS: In bearded individuals, the BVGA provides significantly more efficient (less leak) ventilation compared to a face mask. This is also of particular importance in view of the increasing number of bearded individuals serving in the armed forces. Moreover, since effective ventilation with a mask requires experience, the relatively easy-to-apply BVGA will enable less experienced first responders to achieve higher success rates in this critical phase of treatment. Further studies are planned to evaluate the efficacy of the BVGA in the prehospital setting.

Acute respiratory failure and the kinetics of neutrophil recovery in pediatric hematopoietic cell transplantation: a multicenter study.

In this multicenter study, we investigated the kinetics of neutrophil recovery in relation to acuity and survival among 125 children undergoing allogeneic hematopoietic cell transplantation (allo-HCT) who required invasive mechanical ventilation (IMV). Recovery of neutrophils, whether prior to or after initiation of IMV, was associated with a significantly decreased risk of death relative to never achieving neutrophil recovery. A transient increase in acuity (by oxygenation index and vasopressor requirements) occurred among a subset of the patients who achieved neutrophil recovery after initiation of IMV; 61.5% of these patients survived to discharge from the intensive care unit (ICU). Improved survival among patients who subsequently achieved neutrophil recovery on IMV was not limited to those with peri-engraftment respiratory distress syndrome. The presence of a respiratory pathogen did not affect the risk of death while on IMV but was associated with an increased length of IMV (p < 0.01). Among patients undergoing HCT who develop respiratory failure and require advanced therapeutic support, neutrophil recovery at time of IMV and/or presence of a respiratory pathogen should not be used as determining factors when counseling families about survival.

Correction to: Acute respiratory failure and the kinetics of neutrophil recovery in pediatric hematopoietic cell transplantation: a multicenter study.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The promising future of drones in prehospital medical care and its application to battlefield medicine.

Unmanned aerial vehicles, commonly referred to as drones, have been made widely available in recent years leading to an exponential growth in their roles and applications. The rapidly developing field of medical drones is on the verge of revolutionizing prehospital medicine enabling advanced health care delivery to once-inaccessible patients. The aim of this review is to clarify the basic technical properties of currently available medical drones and review recent advances and their usefulness in military and civilian health care missions. A thorough search was conducted using conventional medical literature databases and nonmedical popular search engines. The results indicate increasingly rapid incorporation of unmanned aerial vehicles into search and rescue missions, telemedicine assignments, medical supply routes, public health surveillance, and disaster management. Medical drones appear to be of great benefit for improving survivability of deployed forces on and off the battlefield. The emerging aerial medical delivery systems appear to provide particularly promising solutions for bridging some of the many serious gaps between third world health care systems and their western counterparts and between major metropolitan centers and distant rural communities. The global nature of drone-based health care delivery needs points to a need for an international effort between collaborating civilian and military medical forces to harness the currently available resources and novel emerging technologies for broader lifesaving capabilities. LEVEL OF EVIDENCE: Level V.

Old Challenges and New Perspectives on Developing Military Physicians: The First 4 Years of the New Israeli Model.

Military medicine comprises a set of unique characteristics that differentiate it from other medical specialties. Faced with challenges in recruiting, educating, and training military physicians, the Israel Defense Forces Medical Corps redefined the paradigm for educating military physicians by establishing the Army Program for Excellence in medicine (APEX). This program created a military medical track at the Hebrew University-Hadassah School of Medicine in Jerusalem. All military track students attend a single medical school, which allows for a more focused and efficient program. The students study, dorm, and train together, forming a strong social network. They also receive significant financial, logistical, academic, and educational support. Finally, the program provides a full curriculum in military medical studies, composed of academic courses given for credits and an integrated training schedule designed to build and improve physical and mental fitness for the military environment. In this article, we provide an overview of APEX, including the admissions process and a descriptive analysis of the student body, and present our comprehensive approach to teaching academic military medicine. To the best of our knowledge, APEX represents one of the few fully integrated undergraduate longitudinal military medical education programs, allowing us to educate military physicians "from day one."