*Edited by Nicolás Padilla-Raygoza*

This book discusses post-COVID health conditions, ranging from mental health issues to central nervous system complications. It also examines prevention strategies such as vaccination and early treatments. There is also a chapter dedicated to the pandemic in Latin America and Mexico, where socioeconomic inequalities may exacerbate the health complications of the virus. This volume is a valuable resource for public health decision-makers and other interested readers.

Published in London, UK © 2023 IntechOpen © Alex Perez / Unsplash

Post COVID-19 - Effects on Human Health

Post COVID-19

Effects on Human Health

*Edited by Nicolás Padilla-Raygoza*


**9. Options for patients with CVS needing VA**

They can change to peritoneal dialysis if feasible. One can plan for thigh AVF or graft. But if both these are not the options, one is left with exploring central venous access with angioplasty and insertion of HD catheters, with TCC or Hemodialysis Reliable Outflow (HeRO®) device. For the purpose of this chapter, we would focus on upper limb CVS. Not to forget the fact that in the presence of SVC stenosis, no AVF or upper limb grafts will be feasible if the SVC stenosis is tight and has a chance for recurrence in spite of SVC angioplasty with or without stent. With improved dialysis survival, there are increasing numbers of patients who have exhausted definitive access options due to central venous stenosis and are maintaining dialysis on a central venous catheter. The HeRO allows an alternative by providing a definitive access solution [16].

## **10. The procedure: approaching and crossing stenosis**

The approach to central vein could be from femoral veins, internal jugular veins, and brachial or cephalic veins. One needs to have thorough history, clinical examination, and Doppler study to arrive at a conclusion about suspected site of CVS. When these are unable to point the site of likely lesion, one may perform contrast-enhanced computer tomography (CT) venogram. The problem with CT venography is the need to inject iodinated contrast. This can be a problem in HD patients at times, who have no peripheral access to inject contrast. In such cases, magnetic resonance (MR) venography without gadolinium, using time-of-flight protocol, may yield equally good results and help plan the procedure. Gadolinium should be avoided in patients with eGFR of <30 ml/min due to risk of nephrogenic systemic fibrosis.

Once the procedure of angiography is decided, one needs to be ready with proper hardware, including various types of wires (0.35 and 0.14 regular and double length wires, hydrophilic wires, and stiff wires), various types of diagnostic and guiding catheters, larger-size high-pressure balloons, stents, or stent grafts. One may need large length vascular sheaths to provide stability to the catheter and guide wire, especially when femoral venous access is used.

#### **10.1 How are the target lesion approached?**

The indications to perform central vein angioplasty are either the patient is symptomatic with functioning vascular access in the upper limb, or the patient has had multiple vascular access failures in upper limb, and no reliable long-term vascular access is available. In such cases, the aim of central vein angioplasty is to create a passage to insert central dialysis catheter, which can be either TCC or hybrid graft if a reliable arterial inflow is available.

If the target lesion is right brachiocephalic vein or SVC, the right IJV is punctured, lesion attempted to be crossed with 0.014′ hydrophilic wire. If that is not successful, the right femoral vein is punctured and the lesion approached. The combination of this approach from either side helps take simultaneous angiographic shoots to define site and extent of lesion in terms of its length and diameter. We have encountered several cases, in which the thinnest of wires, sometimes even the coronary wires, or CTO wires (chronic thrombotic occlusion) fail to cross the lesion. In such cases, recanalization is attempted, which is described as sharp needle recanalization. When traditional endovascular methods fail, experienced interventionalists may utilize sharp or radiofrequency (RF)-assisted recanalization techniques. Sharp recanalization techniques require the use of the back end of a wire, 20- to 22-gauge (15–20 cm) percutaneous or transseptal needles, or transjugular intrahepatic portosystemic shunt needles [17]. In the absence of any other alternatives, we have been doing it with a long Chiba needle. One has to have simultaneous projections in anteriorposterior and lateral views to be sure that the puncture is in the proper venous plain and perforation is avoided. There is no true vessel wall, and a stent is placed to reconstitute the vessel wall if this is being done for upper extremity vascular access preservation. Otherwise, a catheter is inserted after balloon angioplasty of target lesion and creating enough venous diameters to allow smooth passage of the dialysis catheter. Recently, a new device called Surfacer® Inside-Out® access catheter system is available. The Surfacer Device offers a new approach for repeated venous access in patients with thoracic central venous occlusion (TCVOs) that enables the avoidance of left-sided catheter placement in individuals awaiting creation or maturation of permanent AV access or in patients who have exhausted all thoracic venous access options [18]. The author has no personal experience of using it; however, it is meant to restore and preserve access in the chronically occluded veins. Its advantages include restoration and sustenance of access, reliable and repeatable central venous access to the right IJV, preserving viability of secondary central veins, and optimization of the placement and maturation of permanent AV access.

TCVO [19], the authors divided TCVO as type 1, defined as any unilateral obstruction affecting either the internal jugular or subclavian vein. Type 2 includes all cases with ipsilateral occlusion of the brachiocephalic vein or ipsilateral obstruction of both internal jugular and subclavian veins. In TCVO type 3, both brachiocephalic veins are obstructed. Type 4 is characterized by central obstruction of the SVC. Thirtysix patients with TCVO treated in Vienna, Austria; Oxford, England; or Cologne, Germany, who required hemodialysis access between July 2016 and June 2018, with TCVO and history of multiple CVCs and AVF, were referred to the participating centers for vascular access. Thirty-two (89%) patients were eligible for the inside-out

**177**

*Hemodialysis Vascular Access with Central Venous Disease*

procedure of angioplasty is completed.

approach (IOA) approach. Thirty-nine treatments were performed, with seven patients undergoing the IOA procedure for the second time more than 3 months after initial CVC placement. Dialysis access was established successfully in 38 of 39 (97%) implementations of the IOA procedure. Median intervention time was 43 minutes. No complications occurred. This appears to be a promising method, although this was an

If CVS is bypassed, and adequate inflow with axillary artery is available, the HeRO® device can be implanted, which will avoid the need for external TCC and

a.If the target lesion is in the subclavian vein or cephalic arch or left brachiocephalic vein, approach from arm cephalic, basilic, or rarely brachial vein is required, usually combined with femoral vein approach. In cases of tight CTO, to provide adequate support and stability to the procedure of angioplasty, the wire from the arm vein is passed all the way down to the femoral vein and snared out. The hydrophilic wire is then changed over to a stiff wire, and the

b.If attempting to put femoral vein or inferior vena cava (IVC) TCC and dealing with iliac vein or IVC stenosis, approach will be from the femoral vein, and

PTA with balloon dilatation is the primary basis for endovascular therapy. If symptoms are present, PTA is performed; however, patency is poor, so repeat procedures are often required. If it is a first PTA and there is no elastic recoil of the vein on table, one should not consider stenting. Recent studies using intravascular ultrasound (IVUS) for CVS showed that, although the lesion was sufficiently enlarged on angiography after PTA, IVUS demonstrated insufficient dilation or extrusion by the balloon catheter [20]. In such cases, repeat angioplasty with larger-size and higherpressure balloons can be tried, keeping in mind the risk of central venous rupture. Insertion of stents in such situation can be tried. However, numerous studies showed failure of stent use, especially in HD VA, because of neointimal hyperplasia

again recanalization is attempted with thin wire or sharp needle.

within the stent, leading to a lower patency rate than that of PTA [21, 22].

The stent graft (SG) is a structure that applies graft material to the inside or outside of the stent to create a physical barrier to NIH. Various studies and author's experience have been that even the SGs do not provide long-term venous patency. There have been reports of using drug-coated balloons for CVS; however, at pres-

Stenting for TCVO is appropriate in the following situations, provided there are associated hemodynamic or clinical abnormalities: acute elastic recoil (>50%) following PTA and recurrent stenosis within a 3-month period of PTA. If balloon angioplasty achieves insufficient dilation (e.g., severe recoil) or leads to dissection or acute occlusion of the affected vein, bailout stenting is performed. [15]. Balloon angioplasty is a basic treatment for central venous lesion, but stent implantation is sometimes required. The self-expandable or balloon-expandable stent is chosen by the lesion location and characteristics. The lesion in SCV is generally treated by self-expandable stent, and right BCV is treated by balloon-expandable stent. The organic lesion of innominate vein with plaque is treated by self-expandable stent. Note that the innominate venous stenosis is sometimes caused by compression between the right brachiocephalic artery and the sternum and this lesion is treated by balloon-expandable stent because the radial force of balloon-expandable stent is stronger than self-expandable stent. It is important to understand the indication

observational study and no comparison was made to any other methods.

*DOI: http://dx.doi.org/10.5772/intechopen.93030*

minimize risk of CRBSI.

ent, the benefit seems limited.

and stent selection for central venous PTA [15].

*Hemodialysis Vascular Access with Central Venous Disease DOI: http://dx.doi.org/10.5772/intechopen.93030*

*Cardiac Diseases - Novel Aspects of Cardiac Risk, Cardiorenal Pathology and Cardiac Interventions*

Once the procedure of angiography is decided, one needs to be ready with proper hardware, including various types of wires (0.35 and 0.14 regular and double length wires, hydrophilic wires, and stiff wires), various types of diagnostic and guiding catheters, larger-size high-pressure balloons, stents, or stent grafts. One may need large length vascular sheaths to provide stability to the catheter and

The indications to perform central vein angioplasty are either the patient is symptomatic with functioning vascular access in the upper limb, or the patient has had multiple vascular access failures in upper limb, and no reliable long-term vascular access is available. In such cases, the aim of central vein angioplasty is to create a passage to insert central dialysis catheter, which can be either TCC or hybrid graft if

If the target lesion is right brachiocephalic vein or SVC, the right IJV is punctured, lesion attempted to be crossed with 0.014′ hydrophilic wire. If that is not successful, the right femoral vein is punctured and the lesion approached. The combination of this approach from either side helps take simultaneous angiographic shoots to define site and extent of lesion in terms of its length and diameter. We have encountered several cases, in which the thinnest of wires, sometimes even the coronary wires, or CTO wires (chronic thrombotic occlusion) fail to cross the lesion. In such cases, recanalization is attempted, which is described as sharp needle recanalization. When traditional endovascular methods fail, experienced interventionalists may utilize sharp or radiofrequency (RF)-assisted recanalization techniques. Sharp recanalization techniques require the use of the back end of a wire, 20- to 22-gauge (15–20 cm) percutaneous or transseptal needles, or transjugular intrahepatic portosystemic shunt needles [17]. In the absence of any other alternatives, we have been doing it with a long Chiba needle. One has to have simultaneous projections in anteriorposterior and lateral views to be sure that the puncture is in the proper venous plain and perforation is avoided. There is no true vessel wall, and a stent is placed to reconstitute the vessel wall if this is being done for upper extremity vascular access preservation. Otherwise, a catheter is inserted after balloon angioplasty of target lesion and creating enough venous diameters to allow smooth passage of the dialysis catheter. Recently, a new device called Surfacer® Inside-Out® access catheter system is available. The Surfacer Device offers a new approach for repeated venous access in patients with thoracic central venous occlusion (TCVOs) that enables the avoidance of left-sided catheter placement in individuals awaiting creation or maturation of permanent AV access or in patients who have exhausted all thoracic venous access options [18]. The author has no personal experience of using it; however, it is meant to restore and preserve access in the chronically occluded veins. Its advantages include restoration and sustenance of access, reliable and repeatable central venous access to the right IJV, preserving viability of secondary central veins, and optimiza-

guide wire, especially when femoral venous access is used.

tion of the placement and maturation of permanent AV access.

TCVO [19], the authors divided TCVO as type 1, defined as any unilateral obstruction affecting either the internal jugular or subclavian vein. Type 2 includes all cases with ipsilateral occlusion of the brachiocephalic vein or ipsilateral obstruction of both internal jugular and subclavian veins. In TCVO type 3, both brachiocephalic veins are obstructed. Type 4 is characterized by central obstruction of the SVC. Thirtysix patients with TCVO treated in Vienna, Austria; Oxford, England; or Cologne, Germany, who required hemodialysis access between July 2016 and June 2018, with TCVO and history of multiple CVCs and AVF, were referred to the participating centers for vascular access. Thirty-two (89%) patients were eligible for the inside-out

**10.1 How are the target lesion approached?**

a reliable arterial inflow is available.

**176**

approach (IOA) approach. Thirty-nine treatments were performed, with seven patients undergoing the IOA procedure for the second time more than 3 months after initial CVC placement. Dialysis access was established successfully in 38 of 39 (97%) implementations of the IOA procedure. Median intervention time was 43 minutes. No complications occurred. This appears to be a promising method, although this was an observational study and no comparison was made to any other methods.

If CVS is bypassed, and adequate inflow with axillary artery is available, the HeRO® device can be implanted, which will avoid the need for external TCC and minimize risk of CRBSI.

PTA with balloon dilatation is the primary basis for endovascular therapy. If symptoms are present, PTA is performed; however, patency is poor, so repeat procedures are often required. If it is a first PTA and there is no elastic recoil of the vein on table, one should not consider stenting. Recent studies using intravascular ultrasound (IVUS) for CVS showed that, although the lesion was sufficiently enlarged on angiography after PTA, IVUS demonstrated insufficient dilation or extrusion by the balloon catheter [20]. In such cases, repeat angioplasty with larger-size and higherpressure balloons can be tried, keeping in mind the risk of central venous rupture. Insertion of stents in such situation can be tried. However, numerous studies showed failure of stent use, especially in HD VA, because of neointimal hyperplasia within the stent, leading to a lower patency rate than that of PTA [21, 22].

The stent graft (SG) is a structure that applies graft material to the inside or outside of the stent to create a physical barrier to NIH. Various studies and author's experience have been that even the SGs do not provide long-term venous patency. There have been reports of using drug-coated balloons for CVS; however, at present, the benefit seems limited.

Stenting for TCVO is appropriate in the following situations, provided there are associated hemodynamic or clinical abnormalities: acute elastic recoil (>50%) following PTA and recurrent stenosis within a 3-month period of PTA. If balloon angioplasty achieves insufficient dilation (e.g., severe recoil) or leads to dissection or acute occlusion of the affected vein, bailout stenting is performed. [15]. Balloon angioplasty is a basic treatment for central venous lesion, but stent implantation is sometimes required. The self-expandable or balloon-expandable stent is chosen by the lesion location and characteristics. The lesion in SCV is generally treated by self-expandable stent, and right BCV is treated by balloon-expandable stent. The organic lesion of innominate vein with plaque is treated by self-expandable stent. Note that the innominate venous stenosis is sometimes caused by compression between the right brachiocephalic artery and the sternum and this lesion is treated by balloon-expandable stent because the radial force of balloon-expandable stent is stronger than self-expandable stent. It is important to understand the indication and stent selection for central venous PTA [15].

It is also important to remember to choose a proper-sized stent. This is sometimes not possible to judge from the angiographic images, and what appears to be adequate angioplasty could be inadequate in terms of adequate vein diameter. IVUS is sometimes useful to guide the choice of proper balloon or stent size, as what appears to be an adequately treated vein could be having significant underlying stenosis, which is not possible to realize on conventional two-dimensional angiography. IVUS is an invasive modality that provides cross-sectional imaging of the veins but without the need for ionizing radiation or contrast administration. In addition to being a diagnostic tool that is easy and repeatable, it aids treatment decisionmaking. Though IVUS may be better suited than traditional venography to identify intraluminal narrowing and pre-/post-intervention outcomes, additional study is warranted to better characterize the value of IVUS in the VA-related CVS patient population. In a patient with CVS and prior allergy to iodinated contrast, angiography was performed using 1 cc of contrast, CVS confirmed, and the rest of the procedure of angioplasty and confirmation of adequate result was completed using IVUS (personal communication, Dr. Daniel Patel, Interventional Nephrologist, Volusia-Flagler Vascular Centre, Daytona Beach, Florida, USA).

If CRS is the cause for catheter malfunction, the same can be confirmed during catheter exchange procedure by doing pullback angiography prior to full removal of TCC. There can be only CRS, which can be tackled by balloon angioplasty and fibrin sheath disruption. Rarely (and in the authors' own experience), the CRS can be snared out. However, the CRS can be associated with CRAT. And it can become tricky to perform angioplasty, as the risk of pulmonary thromboembolism due to large CRAT, attached to TCC tip, is high. Sometimes, CRAT is attached to the wall of the right atrium. In such a case, if TCC is functioning well, the patient can be anticoagulated and kept under close observation. For a large CRAT or infected CRAT, attached to TCC tip, and where it is risky and not advisable to remove the CRAT, AngioVac thrombectomy device can be used. If these patients are poor candidates for conventional therapy of thrombolytics or surgical thromboembolectomy because of bleeding, failure of thrombolytics, or hemodynamic instability, they may benefit from percutaneous mechanical thrombectomy by AngioVac, which is proved to be effective for complete evacuation in most patients [23].

Surgical options may be considered for CVS, when the stenosis persists, and there are no alternative avenues to provide long-term reliable VA. One must assess the AVF for flow velocity, as this may be the cause of CVD. In such cases, inflow reduction either surgically or percutaneously can be performed. Another surgical option is unusual bypass including reconstruction surgery and claviculectomy or first rib resection if there is thoracic outlet syndrome. If an experienced vascular surgeon is available, the bypass surgery can be performed using graft (PTFE) from the brachial artery to ipsilateral or contralateral internal jugular veins or axillary or femoral veins. Direct connection to SVC or right atrium have also been attempted. One must remember that such surgeries are complicated and carries its own risks and complications.

There are occasions when there is coexistence of CVS and stenosis in the draining vein, either juxta-anastomotic or away from the site of anastomosis. In such situation, one must attempt and achieve patency of CVS lesion. Failure to do so can lead to severe swelling of the ipsilateral arm. The best way to relieve symptomatic CVS is closure of AVF. But it is not possible in patients, who have the last surviving access and shortage of vascular estate.

But, sometimes, there are more than one possible approach to a problem, and the opinion varies as per the specialist handling the case. For example, refer to **Figure 4**, a middle-aged lady on hemodialysis with CVS who had undergone angioplasty with stenting and resolution of right upper limb painful edema. She

**179**

**12. Conclusion**

**Figure 4.**

*Right SCV in-stent thrombosis.*

*Hemodialysis Vascular Access with Central Venous Disease*

1/3rd claviculectomy to relieve her symptoms.

**11. Cardiovascular consequences of AVF**

presented with the same symptoms 6 months later. The angiography image shows in-stent stenosis. It was difficult to negotiate the stenosis. Various opinions were sought. The interventional nephrologist found that it was the high-flow fistula (flow volume 2600 ml/min, very high) which was responsible for her symptoms, and the patient should undergo flow reduction procedure. The interventional radiologist said that attempt to do in-stent angioplasty, followed by stent placement within the stent, should be the first option. The vascular access surgeon said that the stenosis is due to external compression and the patient should undergo middle

Sometimes very-high-flow AVFs can lead to VH, progressive aneurysmal dilatation of vein with skin ulceration, hemodialysis access-induced distal ischemia, and high-output heart failure with or without pulmonary hypertension. AVFs have effects on cardiac functions related to the increase in preload and cardiac output (CO). It is difficult to define cardiovascular consequences due to AVF in a precise manner. This is due to the fact that patients requiring long-term hemodialysis tend to have volume overload due to water and salt retention. There could also be pressure load due to arterial sclerosis and hypertension and increased CO secondary to chronic anemia. In addition, many hemodialysis patients have significant pre-existing myocardial, valvular, or coronary heart disease, as the vascular calcification due to CKD-MBD (chronic kidney disease—mineral and bone disorder). Congestive heart failure (CHF) is highly prevalent among patients with ESRD. Approximately 35–40% of patients with ESRD have an established CHF diagnosis at initiation of hemodialysis. Worsening in cardiac functions soon after AVF creation has also been observed favoring a causative effect of the AVF on certain cardiac functions [24].

CVD is a common occurrence in HD patients, either due to mechanical or hemodynamic factors. It could be related to catheters or AVF. It can be symptomatic or asymptomatic. Interventions will be required in symptomatic patients and in those who have VA malfunction. There are various options, and one needs to choose the modality based on the patient's need. The outcomes cannot be predicted as each vein behaves differently. Proper knowledge of anatomical lesion, pathophysiology of the lesion, patient needs, and expertise available will determine the intervention

*DOI: http://dx.doi.org/10.5772/intechopen.93030*

*Hemodialysis Vascular Access with Central Venous Disease DOI: http://dx.doi.org/10.5772/intechopen.93030*

**Figure 4.** *Right SCV in-stent thrombosis.*

*Cardiac Diseases - Novel Aspects of Cardiac Risk, Cardiorenal Pathology and Cardiac Interventions*

It is also important to remember to choose a proper-sized stent. This is sometimes not possible to judge from the angiographic images, and what appears to be adequate angioplasty could be inadequate in terms of adequate vein diameter. IVUS is sometimes useful to guide the choice of proper balloon or stent size, as what appears to be an adequately treated vein could be having significant underlying stenosis, which is not possible to realize on conventional two-dimensional angiography. IVUS is an invasive modality that provides cross-sectional imaging of the veins but without the need for ionizing radiation or contrast administration. In addition to being a diagnostic tool that is easy and repeatable, it aids treatment decisionmaking. Though IVUS may be better suited than traditional venography to identify intraluminal narrowing and pre-/post-intervention outcomes, additional study is warranted to better characterize the value of IVUS in the VA-related CVS patient population. In a patient with CVS and prior allergy to iodinated contrast, angiography was performed using 1 cc of contrast, CVS confirmed, and the rest of the procedure of angioplasty and confirmation of adequate result was completed using IVUS (personal communication, Dr. Daniel Patel, Interventional Nephrologist,

If CRS is the cause for catheter malfunction, the same can be confirmed during catheter exchange procedure by doing pullback angiography prior to full removal of TCC. There can be only CRS, which can be tackled by balloon angioplasty and fibrin sheath disruption. Rarely (and in the authors' own experience), the CRS can be snared out. However, the CRS can be associated with CRAT. And it can become tricky to perform angioplasty, as the risk of pulmonary thromboembolism due to large CRAT, attached to TCC tip, is high. Sometimes, CRAT is attached to the wall of the right atrium. In such a case, if TCC is functioning well, the patient can be anticoagulated and kept under close observation. For a large CRAT or infected CRAT, attached to TCC tip, and where it is risky and not advisable to remove the CRAT, AngioVac thrombectomy device can be used. If these patients are poor candidates for conventional therapy of thrombolytics or surgical thromboembolectomy because of bleeding, failure of thrombolytics, or hemodynamic instability, they may benefit from percutaneous mechanical thrombectomy by AngioVac, which is

Volusia-Flagler Vascular Centre, Daytona Beach, Florida, USA).

proved to be effective for complete evacuation in most patients [23].

Surgical options may be considered for CVS, when the stenosis persists, and there are no alternative avenues to provide long-term reliable VA. One must assess the AVF for flow velocity, as this may be the cause of CVD. In such cases, inflow reduction either surgically or percutaneously can be performed. Another surgical option is unusual bypass including reconstruction surgery and claviculectomy or first rib resection if there is thoracic outlet syndrome. If an experienced vascular surgeon is available, the bypass surgery can be performed using graft (PTFE) from the brachial artery to ipsilateral or contralateral internal jugular veins or axillary or femoral veins. Direct connection to SVC or right atrium have also been attempted. One must remember that such surgeries are complicated and carries its own risks

There are occasions when there is coexistence of CVS and stenosis in the draining vein, either juxta-anastomotic or away from the site of anastomosis. In such situation, one must attempt and achieve patency of CVS lesion. Failure to do so can lead to severe swelling of the ipsilateral arm. The best way to relieve symptomatic CVS is closure of AVF. But it is not possible in patients, who have the last surviving

But, sometimes, there are more than one possible approach to a problem, and the opinion varies as per the specialist handling the case. For example, refer to **Figure 4**, a middle-aged lady on hemodialysis with CVS who had undergone angioplasty with stenting and resolution of right upper limb painful edema. She

**178**

and complications.

access and shortage of vascular estate.

presented with the same symptoms 6 months later. The angiography image shows in-stent stenosis. It was difficult to negotiate the stenosis. Various opinions were sought. The interventional nephrologist found that it was the high-flow fistula (flow volume 2600 ml/min, very high) which was responsible for her symptoms, and the patient should undergo flow reduction procedure. The interventional radiologist said that attempt to do in-stent angioplasty, followed by stent placement within the stent, should be the first option. The vascular access surgeon said that the stenosis is due to external compression and the patient should undergo middle 1/3rd claviculectomy to relieve her symptoms.


*Probiotics in Processed Dairy Products and Their Role in Gut Microbiota Health DOI: http://dx.doi.org/10.5772/intechopen.104482*

Molecular and antibacterial characterization is analyzed and kept in a test tube that contain 15% (v/v) glycerol at −20°C. Extraction and amplification of bacterial genomic DNA. Different kinds of bacteria colonies emerged on MRS agar surface following screening and phenotypic characterization. Screenings were performed on different 60 MRS agar plates that have tiny, round, matt, and white colonies, it was performed with 70 different biochemical characteristics of LAB showcasing the gram-positive and the catalase negative, including cocci, or in shape rods.


*2.2. Landscape, Soil, and Weather Data*

Landscape, soil, and weather data were collected to determine differences within and between fields for each location-year. Georeferenced landscape, soil, and weather data were assembled from the center point of each sub-plot (strip-plot for Missouri locations) using ArcGIS 10.1 (ESRI, Redlands CA, USA). Sub-plot elevations (m above sea level) were collected from the National Elevation Dataset [29]. Soil water-holding capacity (volume fraction), soil organic matter (%), soil texture, soil depth (cm), field slope, and soil erosion factors were gathered from the Soil Survey Geographic (SSURGO) database [30]. Soil texture data in SSURGO were used to rank textures by coarseness—clay (finest), silt, loam, and sand (coarsest)—using the USDA soil texture calculator [31].

A soil erosion index (SEI) was created using SSURGO [30] data, USDA Revised Universal Soil Loss Equation, version 2 (RUSLE2) data [32], and a modified universal soil loss equation to account for the physical factors of the fields [24]:

$$SEI = \begin{pmatrix} KF \times LS \times R \end{pmatrix} / TF \tag{1}$$

where *KF* is an erodibility factor due to water, *LS* is a soil length (*L*) and slope steepness (*S*) factor, *R* is the rainfall and runo ff factor from USDA RUSLE2 version <IP_ADDRESS> [32]; and *TF* is a soil tolerance factor.

Weather was measured by temperature [33], expressed as seasonal growing degree days. To calculate seasonal growing degree days, the positive values of daily average temperature minus 15.6 ◦C was summed over 1 April through 31 October for each site-year.

#### *2.3. Fertilizer N Management Net Returns*

Net returns for the FP, VRN 1, and VRN 2 treatments were estimated using sub-plot lint yields, fertilizer N rates, lint and N fertilizer prices, and partial budgeting costs for OS and VRN technologies (Table 2). Price and budget data are in real 2013 US dollars indexed using the annual Gross Domestic Product Price Deflator Index [34]. Crop revenues were estimated by multiplying lint yields for each N management treatment by the national average marketing year cotton lint price of USD 1.86 kg−1 received for 2011 through 2014 [35]. EQIP cost-share payments (NRCS precision nutrient management practice code number 590) for each state for 2011 through 2014 were also added to crop revenues. Estimated payments were USD 68.21 ha−1 in Mississippi [36], USD 68.46 ha−1 in Louisiana [37], USD 65.85 ha−1 in Tennessee [38], and USD 32.64 ha−1 in Missouri [39].

 The fertilizer N price is the national average marketing year fertilizer N prices received for 2011 through 2014 [40]. Following Stefanini et al. [24], budgeted skilled operator labor and equipment operating and ownership costs of USD 2.14 ha−1 and USD 2.45 ha−1, respectively, for OS of the crop canopy was assumed for GreenSeeker ™ sensors retrofitted to a boom sprayer measuring 24.7 m wide. The cost of yield monitoring data identifying yield productivity zones in the field was assumed to be used to augment OS information for the VRN 2 prescription and had a budgeted cost of USD 2.73 ha−1. In addition, the budgeted costs of a computer to manage yield monitor data of USD 0.31 ha−1 and reported cost of technical advice for incorporating yield monitor with OS information of USD 12.63 ha−1 [41], respectively, were included in the total cost for VRN 2. The cost of VRN application was estimated to be USD 6.60 ha−1 more than for the FP [41].


**2. Materials and Methods**

*Rock Physics Model Upscaling by Visco-Elastic Model*

Pore fluid dissolution, as an attenuation mechanism of seismic waves, will lead to dissolution and dissolution between gas and its surrounding liquid, which will lead to the attenuation of seismic waves. In the sphere area of each bubble, the gas dissolution rate can be expressed as [7]:

$$dn/dt = -4\Pi r D\_w \left(\mathbb{C}\_w - \frac{P\_f + 2\gamma/r}{RTK\_H}\right) \tag{1}$$

where *dn/dt* is the dissolution rate of gas, *r* is the bubble radius, *Dw* is the diffusion coefficient, *Cw* is the concentration, *Pf* is the pressure in the fluid, *γ* is the surface tension coefficient, *R* is the gas constant, *T* is the temperature, and *KH* is the Henry's Law constant.

Rock physics models provide velocity dispersion between the seismic data and logging data for specific rock properties. Attenuation curve *Qrock(f)* can be used for generating synthetic seismic records:

$$u(t,\omega) = u\_0 \exp(-i\omega t) \exp\left(-\frac{\omega t}{2Q\_{\text{rock}}(f)}\right) \exp\left(\frac{i\omega t}{\pi Q\_{\text{rock}}(f)} \ln\left|\frac{\omega}{\omega\_r}\right|\right) \tag{2}$$

Considering the explicit *Q*(*f*) expression in rock physics model are unavailable, viscoelastic models are upscaled with non-physical meaning parameters. Attenuation properties can then be well modeled by solving the following problem by using least-squares objective function [25,26]:

$$\min \sum\_{f} \left| Q\_{\text{rock}}(f) - Q\_{\text{visco}}(f) \right|^2 \tag{3}$$

SLS model can model most rock physics models [10], and the *QSLS(f)* can be expressed by:

$$Q\_{SLS}(f) = 1 + \frac{(2\pi f)^2 \mathbf{r}\_\sigma^2}{1 + \omega \left(2\pi f\right)^2 \mathbf{r}\_\sigma^2} \mathbf{r} / \frac{(2\pi f) \mathbf{r}\_\sigma^2}{1 + \left(2\pi f\right)^2 \mathbf{r}\_\sigma^2} \mathbf{r} \tag{4}$$

where *τσ* is stress relaxation time, and τ is strain relaxation time. Combining Equations (2) and (3), the upscaled *Q*(*f*) by the SLS model can be derived:

$$\min\_{\pi, \pi\_{\sigma}, L} \sum\_{f} \left| Q\_{\text{rock}}(f) - (1 + \sum\_{l=1}^{L} \frac{(2\pi f)^2 \tau\_{\sigma}(l)^2}{1 + (2\pi f)^2 \tau\_{\sigma}(l)^2} \tau(l)) / (\sum\_{l=1}^{L} \frac{(2\pi f) \tau\_{\sigma}(l)}{1 + (2\pi f)^2 \tau\_{\sigma}(l)^2} \tau(l))^2 \right| \tag{5}$$

where L is relaxation mechanisms, and *τ* = *τε τσ* − 1, *Q*rock(*f*) is the numerically modeled attenuation curve based on the rock physics model. Here, we use the wave-induced gas exsolution–dissolution (WIGED) model to calculate the *Q*rock(*f*), and the parameters used are listed in Table 1. The volumetric strain of the pore fluid is calculated, followed by the modulus *K*, and attenuation can be obtained by *Q*(*f*)−1 = *Im*(*K*(*f*)) *Re*(*K*(*f*)) .

**Table 1.** Parameters used in three rock physics models: the pore fluid dissolution model, the SLS model and the Pride model.

Well-to-seismic calibration based on rock physics model upscaling. The misfit between the seismic data and the logging data can then be calibrated by implementing the following procedures (Figure 1):

**Figure 1.** Procedures of the proposed well-to-seismic calibration method.

### **3. Synthetic Data Test**


**1. Introduction**

Near-infrared spectroscopy (NIRS) is a spectroscopic technique which uses the NIR region of the electromagnetic spectrum to gain information about natural samples through their absorption of NIR light. This method is used in several branches of science. In medicine, it was first used in adult patients, who were placed on by-pass during cardiac surgery to follow cerebral oxygenation, cerebral rSO2 (rSO2-c,) and thereby perfusion and metabolism of the brain. Its many other possibilities soon became apparent. Although the brain remains the main organ of interest in patients of all ages, other tissues are being studied as well. Aside from cardiac surgery clinicians in specialties such as sports medicine, plastic surgery (to assess flap viability), and neonatology apply NIRS in clinical settings. (Feng et al., 2001)

By the late 1980's the first studies on monitoring of regional oxygenation in the neonatal brain were published. (Delpy et al., 1987; Edwards et al., 1988) In 2004 on average one new article on NIRS was published in Pub Med every day. (Ferrari et at, 2004) Monitoring of vital signs in the ICUs has scientific and patient care related goals. One may be able to gain better understanding of physiology and be alerted to changes in patient status to be able to respond immediately.

The vulnerability of the neonate, especially of the newborn brain, to changes in oxygenation is an ever present concern as it is linked to long-term outcome. For that reason neonatologists are obligated to find ways to monitor their patients to be ahead of evolving pathology and avoid the severe impact of negative events.

As early as 1999 the NINDS and NIH hosted a workshop for experts in the fields of neurology and neonatology to discuss the use of NIRS for cerebral monitoring in infants. The panel determined that the best NIRS instrument should be selected and used in longitudinal, blinded studies. Obtained data would need to be compared with short term, intermediate and long term outcomes. The questions the panel suggested to investigate were the predictive value of NIRS and its usefulness in leading to timely interventions and prevention of long term injury. (www.ninds.nih.gov/news\_andevents/proceedings/

Use of Near-Infrared Spectroscopy in the Management of Patients in

or tissue oxygenation index (TOI).

al., 2006)

**1.3 Validation**

Neonatal Intensive Care Units – An Example of Implementation of a New Technology 7

NIRS monitors with somewhat different technology and algorithms available commercially (Wolf & Greisen, 2009) to measure the venous weighted regional oxygen saturation (rSO2)

Due to the small size and the thin covering layers of tissue of both term and preterm neonates, r-SO2/TOI measurements at a depth of 2-3 cm can reach brain, kidney, gut/ splanchnic circulation, liver and muscle. The access to these critical organs promises valuable physiologic information through monitoring by NIRS. Measurements of several sites can be recorded simultaneously. (Hoffman et al., 2003; McNeill et al., 2010, 2011)

NIRS measurements are organ specific and regional (rSO2), reflecting perfusion and metabolism by non-invasive measurement in real-time. They are not temperature, pulsatility or flow dependent. Thus they may offer advantages over traditional measures of perfusion such as capillary refill, blood pressure, and urine output, lactate, venous and arterial O2 which tend to alert the clinician once the disease process is further progressed. R-SO2 measurements cannot stand alone. While they may often be the first sign of change, they need to be interpreted in the context of other measurements such as mean arterial blood pressure (MABP), pulse oximetry (O2sat), blood gases, additionally in the research setting with measurements of cerebral blood flow (CBF) and cerebral blood volume (CBV). Evaluation of the link between the venous weighted NIRS readings and peripheral pulse oximetry, a measure of arterial O2, gives insight into oxygen supply and demand. Using a simple equation, the fractional extraction of oxygen (FTOE = SaO2-rSO2/SaO2) oxygen consumption can be calculated and oxygen supply can be assessed. (Lemmers et

NIRS was implemented by many enthusiastic clinicians without a vast body of previous research evidence. This phenomenon may be representative of an era of limited funding for larger studies linked with the promise of a non-invasive "safe" monitoring technology.

Before human application the initial research applying NIRS to measure rSO2 technology in the medical field occurred in the laboratory: One of the first examples of validation used a phantom brain model in which O2, N2, and CO2 content of a blood perfusate could be altered during measurements. The results correlated with findings in animal models. (Kurth et al., 1995) Later NIRS was further validated for the neonatologist in a newborn piglet model. The carotid, renal and mesenteric arteries were occluded and reperfused. These interventions led to rapid, simultaneous changes in rSO2 of the affected end-organs. (Wider, 2009) Furthermore, there have been validations in patients during intensive care, extracorporeal membrane oxygenation (ECMO) and cardiac surgery by comparing central blood samples with NIRS values. (Abdul-Khaliq et al., 2002; Benni et al., 2005; Nagdyman et al., 2004; Rais-Bahrami K et al, 2006; Weiss, 2005) Menke found reproducibility to be good as well. (Menke et al., 2003). The accuracy of data is impacted by light scattering, hemoglobin concentration and chromophores such as melanin and bilirubin. In the presence of a thicker overlying tissue layer, such as severe subcutaneous edema or excess subcutaneous fat, it may be impossible for the NIR light beam to reach the target organ. In the newborn modest changes in weight have a small effect on abdominal measurements while changes in hemoglobin over the first weeks of life can change measurements by 30-50%. (Ferrari et al.,

nirswkshop1999.htm) Once NIRS monitors became commercially available a few animal and many clinical trials were conducted. The clinical investigations were for the most part small, brief observational prospective studies. Also NIRS was introduced into daily practice by others at that time, years before normative data and validation studies had been obtained.

There is great potential to use the NIRS technology in the neonatal intensive care unit (NICU) since it is a portable, continuous, non-invasive bedside monitoring technique. Following the development of small and skin friendly sensors and FDA approval of some NIRS monitors for use in neonates, both research and clinical use of NIRS in the NICU increased exponentially. The number of research projects over the last 5-10 years is large. However, the trials, while dealing with questions important to understanding physiology and clinical care in the NICU, are small and almost exclusively conducted at single centers. Often no more than 10-20 patients are being followed. Very large NIRS related studies enrolled 40-90 patients. Many of the observations reported are of brief sampling periods, sometimes being no more than spot samples.

This chapter is a limited overview for non-clinicians such as engineers and science students, or clinicians who want to learn about a medical application of NIRS. The recent introduction of the NIRS technology into neonatal medicine is used as an example of how a new device came into use into use in the clinical setting over the last decade. Main areas of clinical use and supporting studies will be mentioned. Limitations of NIRS technology and controversies as well as future directions will be addressed. With the abundance of available literature this chapter cannot claim to be a reference. This is an exciting and rapidly advancing field with new studies published even as this article was sent to press. This chapter will demonstrate how a new technology is adopted into medical care, in this case the NICU.

### **1.1 Materials**

Pub Med and Google have been queried regarding NIRS in NICUs, abdominal/splanchnic, cerebral and renal measurements, utility, and of NIRS use as prognosticator.

#### **1.2 Technology and measurements**

The principle of how NIRS works in humans was excellently summarized by Cohn:

Near-infrared spectroscopy has been used as a tool to determine the redox state of lightabsorbing molecules. This technology is based on the Beer-Lambert Law, which states that light transmission through a solution with a dissolved solute decreases exponentially as the concentration of the solute increases. In mammalian tissue, only three compounds change their spectra when oxygenated: cytochrome *aa3*, myoglobin, and hemoglobin. Because the absorption spectra of oxyhemoglobin and deoxyhemoglobin differ, their relative concentrations within tissue change with oxygenation, and the relative concentrations of the types of hemoglobin can be determined. Because NIRS measurements are taken without regard to systole or diastole, and because only 20% of blood volume is intra-arterial, spectroscopic measurements are primarily indicative of the venous oxyhemoglobin concentration. In the near infrared region (700 –1,000 nm), light transmits through skin, bone, and muscle without attenuation. (Cohn et al., 2003) There are several FDA approved NIRS monitors with somewhat different technology and algorithms available commercially (Wolf & Greisen, 2009) to measure the venous weighted regional oxygen saturation (rSO2) or tissue oxygenation index (TOI).

Due to the small size and the thin covering layers of tissue of both term and preterm neonates, r-SO2/TOI measurements at a depth of 2-3 cm can reach brain, kidney, gut/ splanchnic circulation, liver and muscle. The access to these critical organs promises valuable physiologic information through monitoring by NIRS. Measurements of several sites can be recorded simultaneously. (Hoffman et al., 2003; McNeill et al., 2010, 2011)

NIRS measurements are organ specific and regional (rSO2), reflecting perfusion and metabolism by non-invasive measurement in real-time. They are not temperature, pulsatility or flow dependent. Thus they may offer advantages over traditional measures of perfusion such as capillary refill, blood pressure, and urine output, lactate, venous and arterial O2 which tend to alert the clinician once the disease process is further progressed. R-SO2 measurements cannot stand alone. While they may often be the first sign of change, they need to be interpreted in the context of other measurements such as mean arterial blood pressure (MABP), pulse oximetry (O2sat), blood gases, additionally in the research setting with measurements of cerebral blood flow (CBF) and cerebral blood volume (CBV). Evaluation of the link between the venous weighted NIRS readings and peripheral pulse oximetry, a measure of arterial O2, gives insight into oxygen supply and demand. Using a simple equation, the fractional extraction of oxygen (FTOE = SaO2-rSO2/SaO2) oxygen consumption can be calculated and oxygen supply can be assessed. (Lemmers et al., 2006)