Home Simulation Software Architecture in association with Robot Frank
in development: Kernel, Nozzle, Patent Download & Documentation Resource: Script

Robot


Robot (in association with Software Component, as in Software Architecture) (A) a.k.a. Surgical Robot
(B) Echocardiography
(C) ECMO (ExtraCorporeal Membrane Oxygenation)


(A) a.k.a. Surgical Robot top

Robotic Surgery

RCT Meta-analysis: Robotic vs. Laparoscopic Surgery (Frank, 2018)


Why the thoracic cavity for hemodynamic software and robotic surgery?

The thoracic cavity is intriguing in regards to its demanding physiological and computational potential. It is physiologically intriguing how the lungs and the heart are directly governed by the laws of physics: the hemodynamics during blood circulation and respiration with relation to auscultation, electrocardiography, ECMO and anesthetic machines. Computationally, a kernel-level device driver and Bayesian-based machine learning algorithm can be employed for (1) monitoring of the states of the thoracic organs, (2) computer-assisted hemodynamic modeling and simulation, and (3) machine learning for information processing. In addition, the thoracic cavity is ideal for a specialty that sits on the cusp between surgery and engineering to perform intellectually and technically challenging surgical robotic R&D projects on the organs encased by bones, which are best accessed and manipulated by a thin robotic hand instrument with ergonomic advantages. This will widen the indication of robotic cardiovascular surgery with new surgical procedures that integrate various additional hemodynamic devices and computational support.

"Surgeons must progress beyond the traditional techniques of cutting and sewing that have been their province since surgeons were barbers to a future in which approaches involving minimal access to the abdominal cavity are only the beginning." - Pappas et al. (2004) N Engl J Med.


Robotic surgery cost, under the hood

With respect to the cost-effectiveness of robot-assisted laparoscopic surgery (RLS), it is generally perceived that RLS is more expensive. This may naturally have posed the question of whether RLS is worth employing further in spite of the public concern of not having advantages in complications and conversion with a greater amount of operative time. However, from the perspective of patients, although numerous articles closely compared total operative cost between RLS and conventional laparoscopic surgery (CLS), not only did I find it too complicated to find common objective ground - let alone the exchange rate at the time of having surgery (Morino, 2006) - but also established that the information is not so practical from the perspective of the patients, since total operation cost is not exactly equal to the actual payment by patients per their insurance policy, which varies between different insurance companies, hospitals, and countries. For the former, Aboumarzouk et al. mentioned in his meta-analysis that the so-called total cost did not reflect the context of "social cost analysis" from the implications of a quicker recovery and shorter convalescence (Aboumarzouk, 2012).
    Similarly, from the perspective of hospitals, the profit of hospitals for RLS should comprehensively consider not only, quantitatively, the operation cost for equipment, operation time, the cost of training surgeons in CLS and RLS per respective learning curves, the effect of RLS's longer operative time on the hospital revenue, hospital stay, blood loss, and insurance policy, but - equally importantly, qualitatively - the surgeon's safety from infection such as HIV, repeated radioactive exposure from bed-side X-rays and the comfort of surgeons during the surgery by sitting on chairs. Lin et al. stated similarly that insufficient data and great heterogeneity from differences in skill, extension of lymph node dissection, and duration of the learning curve precluded a meta-analysis of cost-effectiveness (Lin, 2011). In addition, the non-replaceable property of RLS for remote-surgery in the case of war and rural areas should not be left unconsidered. Furthermore, as we all know empirically, the cost of a new technology will eventually decrease over decades. From the perspective of the public or investors in surgical robotics, I suggest that the aforementioned factors under the hood be considered for the cost-effectiveness of robotic surgery.


My general subjective opinion on surgical robotics

It may be surprising that the old criticisms of laparoscopic pioneers in the 1950-1990s are very similar to that being expressed regarding surgical robotics, as most of the criticisms for conventional laparoscopic surgery (CLS) can also be applied to robot-assisted laparoscopic surgery (RLS) including "higher complication rates than laparotomies ... attributable mainly to inexperience, and [e]ach procedure normally done via laparotomy [being] re-invented [with] trial and error" (Page, 2008). Despite harsh criticisms in the late 20th century, CLS has now become widely acknowledged as an indispensable surgical method (Pappas, 2004). Thus, similar to the history of CLS, it still remains to be seen, since there may be room for RLS to move toward better clinical outcomes in the future with ever-accumulating knowledge and experience with trial and error in society overall, especially considering that the industry has now entered the era of industry 4.0, or robotics.




(B) Echocardiography top

A logistic-based systolic model for a pulmonary circulation (Frank, 2018)

Induced (1) Logistic-based systolic model on pulmonary circulation


Proposed (2) for PAP estimation by PAcT of Echocardiography


Its relevant material: (3) Hemodynamic simulator (Prototype in 2016)




Python-based tool to measure Echocardiographic Indices (Frank, 2016)

Measuring and analyzing Echocardiographic hemodynamic indices (prototype)

EchoRuler.py is a python script designed to measure the time and distance on the printouts from echocardiography. Instead of using a physical ruler, this software takes the scanned image of the echocardiographic printout, performs the calibration for time and distance initially, and then computes the actual time and distances per calibrations in return.


Illustration of computing actual distances considering concentric distance field

With respect to the LV eccentricity index, two diameters on the left ventricular cavity can be drawn at the level of the papillary muscle, for which EchoRuler.py will compute the actual distances considering the concentric distance field. Similarly, regarding the acceleration time, you can draw a line to measure the acceleration time, ejection time, and RR-interval.




(C) ECMO (ExtraCorporeal Membrane Oxygenation) top

ECMO meta-analysis on hazard ratios: Cardiopulmonary Diseases (Frank, 2020)

Extracorporeal membrane oxygenation meta-analysis of time-to-event data in cardiopulmonary disease in adults

   In recognition of the benefits of extracorporeal membrane oxygenation (ECMO)[1], clinical outcomes have been the subject of multiple meta-analyses. Previous meta-analyses of ECMO treatment reported forest plots based on relative risks. Unlike a hazard ratio (HR), a relative risk does not consider the time to event and censoring and runs the risk of not using all the available information[2]. In other words, with respect to the patient mortality, the relative risk between ECMO and no-ECMO patient groups cannot avoid overlooking the critical factor of how ECMO has influenced the timing of each event or patient death over the course of disease progression.
   Previous meta-analyses have focused on a single indication presumably because, given the wide range of potential applications for ECMO, studying a particular patient population separately is a crucial step in terms of reducing confounding factors. The present study endeavors to investigate ECMO indications of cardiopulmonary disease as a whole and to list the findings of ECMO mortality in individual indications as subgroup analyses. This was done to ensure that a positive result of a particular indication is not automatically applied to a different patient population that may not have the same benefit, and thereby to prevent a potentially unnecessary intervention. Based on the ECMO indications[3, 4], the present study applies time-to-event data to evaluations of both the overall and individual cardiopulmonary indications of ECMO in adult patients in relation to relevant meta-analyses.
   To the best of our knowledge, the present meta-analysis is the first attempt to use time-to-event HR data to illustrate a forest plot of all-cause mortality from the use of ECMO in adult patients, in terms of both overall cardiopulmonary indications and individual indications as a subgroup analysis. As shown by the results of the overall analysis, across various indications of ECMO in cardiopulmonary diseases in adults, outcomes favored neither the ECMO group nor the no-ECMO group. However, as to the subgroup analyses, the reduction in mortality in the ECMO group was found in respiratory failure, whereas increased mortality in the ECMO group was noted in post-LTx, bridge to HTx, and post-HTx.
   These results should be understood not only in the context of weighing the benefits and adverse effects of ECMO, but also in consideration of patient selection issues. We could not help but notice the propensity to allocate the ECMO treatment to the poor patient conditions. In other words, the no-ECMO groups were selected and specified as groups of patients who required no invasive support[23, 24, 49]. Presumably, this was so because, in a daily practice, ECMO are used in desperate cases such as a cardiogenic shock where, without ECMO implantation, the mortality is critically high. This discriminate propensity of ECMO allocation appears to reflect the wide recognition of the benefits of ECMO treatments[1]but, at the same time, indicates a patient selection bias issue of a meta-analysis on the retrospective studies. Therefore, in addition to the intrinsic benefits and adverse effects of ECMO treatment, biased allocation of ECMO based on patient conditions as a whole appeared to contribute to the aforementioned results.
   In this regard, the significant reduction in mortality of the ECMO group in the patients with respiratory failure compared with the no-ECMO group is worthy of mention. That is, against the patient selection biases that presumably favor the superior outcome in the no-ECMO group, the significantly improved patient outcomes in respiratory failure in the concurring ECMO group is evident. Our result favoring the ECMO group in respiratory failure is consistent with previous meta-analyses for H1N1 pneumonia[65]and ARDS[66]. It can be tentatively proposed thatthe inclusion of the two RCTs, which is less apt to be influenced by the patient selection bias, may contribute to the significant reduction in mortalityof the forest plot due to the increased statistical power of the pooled studies. In addition,Annichet al.stated that themajority of patients with respiratory failure including ARDS has been well supported with veno-venous (V-V) ECMO[1]. In this regard, the increased likelihood of normal cardiac function in respiratory failure conditions could enable the more frequent use of V-V ECMO (or all the use of V-V ECMO[22]), which could avoid the complications of veno-arterial (V-A) ECMO, such as systemic embolization, arterial trauma, and increased left ventricular afterload[67, 68]. However, in consideration ofnumerous possible confounding factors of heterogeneities that may have influenced the mortality results, this hypothesisneeds to be enlightened by more meticulous reasoning that unleashes which factorscontributed to this deviation of respiratory failure subgroup analysis from the overall global analysis.
   Although we are aware of the fact that other ECMO meta-analyses conducted database searches on PubMed, EMBASE, Cochrane, and so forth, we searched against the PubMed database only[69], due to the following reasons. During the pilot study, we found that this study required quite an inclusive search of keywords for various cardiopulmonary ECMO indications, compared with meta-analyses on a single indication, as manifested by the total number of articles we worked with. In addition, unlike meta-analyses on relative risks and mean differences, a full-text was laboriously required to confidently make a decision to exclude its corresponding article, because the survival analysis is usually not the main topic of the referenced study but typically comprising just one line of hazard ratio information in the result table or one Kaplan-Meier survival curve figure. Nonetheless, we acknowledge that the risk of missing appropriate articles by not searching against multiple databases could have lowered the reliability of our study[70].
   Whenever HRs and their variances were not reported explicitly, we estimated them from the information reported in the studies. Therefore, the significance of the results of the forest plot should have been diminished by our estimates of HR and variances. In further research, reporting numerical hazard ratios explicitly to facilitate later meta-analysis should be encouraged to investigate the mortality associated with ECMO use.







ECMO meta-analysis on hazard ratios: Respiratory failure (Frank, 2020)

Extracorporeal membrane oxygenation meta-analysis of time-to-event data in respiratory failure in adults

In recognition of the benefits of extracorporeal membrane oxygenation (ECMO) [1], clinical outcomes have been the subject of multiple meta-analyses. Respiratory failure incorporates 'oxygenation failure' of acquiring oxygen and 'ventilatory failure' of eliminating carbon dioxide [2], which are, respectively, exemplified to ECMO indications of "acute respiratory disease syndrome" (ARDS) and "hypercapnic respiratory failure" [3, 4]. The controversial efficacy of ECMO on patient mortality in respiratory failure has been statistically assessed by previous meta-analyses based on relative risks [5-9].
   Unlike a hazard ratio (HR), the relative risk does not consider the time to event or censoring and runs the risk of not using all the available information [10]. In other words, with respect to patient mortality, the relative risk between ECMO and non-ECMO patient groups cannot avoid overlooking the critical factor of how ECMO has influenced the timing of each event or patient death over the course of disease progression. In consideration of heterogeneities such as veno-arterial (VA) and veno-venous (VV) types, this present study applies time-to-event data to evaluations of the utility of ECMO in patients with respiratory failure.
   To the best of our knowledge, the present meta-analysis is the first attempt to use time-to-event data to illustrate a forest plot of mortality from the use of ECMO in adult patients, comprising both VA type and a majority of VV type, in respiratory failure of 'oxygenation failure' and 'ventilatory failure', compared against no ECMO group. When confining to only VV-ECMO, significant reduction in mortality was also noted.
   These results should be understood not only in the context of weighing the benefits and adverse effects of ECMO, but also in consideration of patient selection issues. Although the propensity to allocate the ECMO treatment to poor patient condition was not explicitly located in the referenced studies [27-31], the non-ECMO groups were reportedly selected and specified as groups of patients who required no invasive support [33-35]. This discriminate propensity of ECMO allocation appears to reflect the wide recognition of the benefits of ECMO treatments [1] but, at the same time, indicates a patient selection bias issue of a meta-analysis on the retrospective studies. Therefore, in addition to the intrinsic benefits and adverse effects of ECMO treatment, biased allocation of ECMO based on patient conditions as a whole appeared to contribute to the aforementioned results.
   In this regard, the significant reduction in mortality of the ECMO group in the patients with respiratory failure compared with the non-ECMO group is worthy of mention. Although VV-ECMO could avoid the complications of VA-ECMO, such as systemic embolization, arterial trauma, and increased left ventricular afterload [36, 37], even VV-ECMO alone is still associated with risk of haemorrhage [27, 28, 30] and circuit-associated complications [5]. That is, against the known complications of the ECMOs and the patient selection biases that presumably favor the superior outcome in the non-ECMO group, the significantly improved patient outcomes in respiratory failure in the ECMO group is evident. Our result favoring the ECMO group in respiratory failure is consistent with previous meta-analyses for H1N1 pneumonia [7] and ARDS [5]. It can be tentatively proposed that the inclusion of the two RCTs, which is less apt to be influenced by the patient selection bias, may partially contribute to the significant reduction in mortality of the forest plot due to the increased statistical power of the pooled studies. In addition, the majority of ECMO in the referenced studies was veno-venous type, possibly due to the increased likelihood of normal cardiac function in respiratory failure conditions, which enable the more frequent use of VV-ECMO (or only the use of VV-ECMO [30]) and could avoid the complications of VA-ECMO. However, in consideration of numerous possible confounding factors of heterogeneities that may have influenced the mortality results, this hypothesis needs to be enlightened by more meticulous reasoning which unleashes what factors contributed to the positive results of respiratory failure indication.
   In reality, the number of ECMO studies tend to be small compared to those on relative risks, and relevant mortality studies on ECMO were not always explicitly designed to meet one subcategory of respiratory failure classification, such as 'ARDS' and 'acute respiratory failure', strictly and mutually exclusively. Thus, the scope of this current study on respiratory failure comprises mortality of respiratory failure by either 'oxygenation failure' or 'ventilation failure.' In the meanwhile, technically speaking, respiratory failure type III occurs during perioperative periods that can be related to cardiopulmonary ECMO indications, to name a few, of "bridge to lung transplantation" [3, 4]; while respiratory failure type IV results from shock, which can be related to "myocardial infraction-association cardiogenic shock" [3, 4]. Nonetheless, for more focused investigation, this study condenses to the mortality of hypoxemic (type I: oxygenation failure) and hypercapnic (type II: ventilation failure) respiratory failure.
   Although we are aware of the fact that other ECMO meta-analyses conducted database searches on PubMed, EMBASE, Cochrane, and so forth, we searched against the PubMed database only [38], due to the following reasons. During the pilot study, we found that this study required quite an inclusive search of keywords, as manifested by the total number of articles we worked with. In addition, unlike meta-analyses on relative risks and mean differences, a full-text was laboriously required to confidently make a decision to exclude its corresponding article, because the survival analysis is usually not the main topic of the referenced study but typically comprising just one line of hazard ratio information in the result table or one Kaplan-Meier survival curve figure. Nonetheless, we acknowledge that the risk of missing appropriate articles by not searching against multiple databases could have lowered the reliability of our study [39].
   Whenever HRs and their variances were not reported explicitly, we estimated them from the information reported in the studies. Therefore, the significance of the results of the forest plot should have been diminished by our estimates of HR and variances. In further research, reporting numerical hazard ratios explicitly to facilitate later meta-analysis should be encouraged to investigate the mortality associated with ECMO use.
   Based on the time-to-event data of respiratory failure, ECMO comprising both VV and VA types and the VV type alone has shown to provide advantages over alternative therapy. Although VV-ECMO alone on respiratory failure was mainly addressed in this study, future investigation of the efficacy of VA-ECMO alone in respiratory failure may be more informative, due to being a more common modality of ECMO yet with greater complications [5]. The accumulation of ECMO time-to-event data studies in respiratory failure will enable more focused mortality assessments, for example, on ARDS, exclusively.

It is acknowledged that the ECMO technology from 1975 has changed immensely such that mortality may be correlated with the year, which is exemplified in the improved mortality over years in-between 1995 -2000 and 2001 -2004 [32]. For the referenced studies, the meta-regression analysis of the midpoint of the study period versus the hazard ratio (Figure 5) illustrates an insignificance (p-value = 0.8011) and neither positive nor negative correlation (r = 0.0635) in the scope of this study.



top

© nGene Hemodynamic Research Center 2013
Project nGene.org® is a registered trademark.