2018 JAPAN Critical Limb Ischemia Database (JCLIMB) Annual Report

Since 2013, the Japanese Society for Vascular Surgery has started the project of nationwide registration and tracking database for patients with critical limb ischemia (CLI) who are treated by vascular surgeons. The purpose of this project is to clarify the current status of the medical practice for patients with CLI to contribute to the improvement of the quality of medical care. This database, called JAPAN CLI Database (JCLIMB), is created on the National Clinical Database and collects data of patients’ background, therapeutic measures, early results, and long-term prognosis as long as 5 years after the initial treatment. The limbs managed conservatively are also registered in the JCLIMB, together with those treated by surgery and/or endovascular treatment. In 2018, 1,145 CLI limbs (male 758 limbs, 66%) were registered by 90 facilities. Arteriosclerosis obliterans has accounted for 97% of the pathogenesis of these limbs. In this manuscript, the background data, ischemic status, treatment, and the early prognosis (within 1 month) of the registered limbs are reported. (This is a translation of Jpn J Vasc Surg 2020; 29: 365–393.)


Introduction
Recently, an increasing number of patients with critical limb ischemia (CLI) are undergoing medical care at clinical practice sites.Improving the outcome of treatment for these patients is an important and urgent issue.Since 2013, the Japanese Society for Vascular Surgery (JSVS) has initiated the project of a nationwide CLI registration and tracking database to obtain CLI epidemiological data that can be shared among the medical staff.The background of CLI limbs, contents of treatment, early outcome, and long-term outcome until 5 years after surgery, including non-surgical limbs, are registered in this database.The database was named JAPAN CLI Database (JCLIMB) and established on the National Clinical Database (NCD).The JCLIMB projectʼs primary objective is to clarify the current status of CLI treatment performed by vascular surgeons in Japan and inform physicians at practice sites, thus improving the quality of medical care.[3][4][5] This article reports the basic data registered in 2018.

JCLIMB
Registration details, including the definition of CLI, have already been described in the 2013 annual report. 1)CLI to be registered was defined according to the TASC II classification 6) : chronic ischemic rest pain, ulcers, or gangrene attributable to objectively proven arterial occlusive disease.CLI diagnosis should be confirmed by ankle pressure (AP) below 50 mmHg or by toe pressure (TP) below 30 mmHg in the limbs with rest pain and done by AP below 70 mmHg or by TP below 50 mmHg in the limbs with ulcer or gangrene.
The same limb can be registered in the JCLIMB only once within a 5-year tracking period.When the registered limb is treated at different times or at different institutions, such data should be added only to the tracking items of each limb in the JCLIMB, avoiding registration overlap.However, details of the procedure are registered each time in the NCD apart from the registration in the JCLIMB.On the other hand, the patient with bilateral CLI can be registered twice for each limb.Based on the NCD regulations, fixing the JCLIMB data are done as follows: Initial registration data: early April in the following year, tracking data early after treatment (1 month)/6 months after treatment: end of December in the following year, tracking data 1 year after treatment: end of Decem-ber after 2 years.
Tracking data 2 years after treatment: end of December after 3 years Tracking data 3 years after treatment: end of December after 4 years Tracking data 4 years after treatment: end of December after 5 years Tracking data 5 years after treatment: end of December after 6 years.As a general rule, the timing of tracking data registration is accepted within a ±2-month range until 12 months after treatment and within a ±3-month range thereafter.Although the day for tracking data fixing is specified, it is made flexible because, in some limbs, follow-up data might be revealed later.
It is very difficult to require facilities participating in the NCD to register CLI data since a great number of registration items in the JCLIMB would put too much burden on them.Thus, facilities wishing to participate were recruited.In total, 90 facilities, which registered CLI limbs in 2018 at the time of compiling in September 2020, are listed in the appendix.
Since the JCLIMB is positioned as a registry study on the NCD, patient consent to participate in the study and the ethical review of the study at the time of participation in the NCD were adopted.

Comments on the Aggregated Data in 2018
The initial registration data in 2018 were fixed in early April 2019, and the tracking data early after treatment (1 month) were fixed on December 31, 2019.At that time, 1,145 limbs, those of 758 males (66%) and 387 females (34%), were registered in 90 facilities.All data and extracted data on arteriosclerosis obliterans (ASO) were collected according to the registered items.Since ASO accounted for 97% of all limbs, the overall and ASO data showed similar tendencies.In the comments, ASO data were presented in parentheses.In addition, because the Society for Vascular Surgeryʼs (SVS) WIfI classification was reported in 2014 (Tables 1-1-1 to 1-1-3), 7) the JCLIMB made several changes and additions to the registered items, making the WIfI classification possible since 2015 (Tables 1-2-1 to 1-2-3).The total figure was not always consistent, mostly due to missing values, and an explanation for each inconsistency was added.

(1) Pretreatment patientsʼ background
Pretreatment patientsʼ background is shown in Tables 2-1 to 2-6.Good blood pressure control was defined as below 140/90 mmHg, without diabetes and renal failure, or below 130/80 mmHg with these diseases.Diabetes control was considered good when hemoglobin A1c was below 7.0% (National Glycohemoglobin Standardization Program value).Dyslipidemia control was considered good when low-density lipoprotein was below 100 and 80 mg/dL in the absence and presence of other arteriosclerotic diseases, respectively.The presence of heart failure was judged clinically.The patient was regarded as having heart failure based on a history of admission due to heart failure, clinical symptoms of heart failure, a diagnosis of heart failure was confirmed by echocardiography, or reduced cardiac function on echocardiography even with no clinical heart failure symptoms.Renal dysfunction was graded following the new chronic kidney disease severity classification of the "Clinical Practice Guidebook for Diagnosis and Treatment of Chronic Kidney Disease 2012" 8) : renal dysfunction was absent when the estimated glomerular filtration rate (eGFR) (mL/min/1.73m 2 ) was 60 or higher, and it was graded as G3a, G3b, G4, and G5 when eGFR was 45-59, 30-44, 15-29, and below 15, respectively.An eGFR below 15 in hemodialysis patients was graded as G5D.

(2) Conditions of limb ischemia
Limb ischemia pretreatment conditions are shown in Tables 3-1 to 3-6.Regarding the walking function (Taylor classification), 9) patients who could walk outdoors or indoors independently, including with a cane, were regarded as "ambulatory," and those unable to walk but able to stand on their own legs during transfer from the bed to a wheel chair were designated as "ambulatory/homebound." Regarding the state of local tissue defect (Texas University classification), 10) the most severe lesion, the main treatment target, was evaluated.Skin perfusion pressure (SPP) was measured on the foot (base of the toe, dorsum of the foot, or sole), and a lower value was adopted.To perform the WIfI classification, the sites of ulcer and gangrene were registered separately.Although SPP is widely used as an objective index for evaluating ischemia in Japan, ischemic grading criteria using SPP is not shown in the WIfI classification, in which TP is given top priority.
The Japanese Society for Vascular Surgery JCLIMB Committee, NCD JCLIMB Analytical Team Therefore, in the JCLIMB, the SPP value was converted to TP using the conversion equation SPP=0.6853×TP+14.48 from the correlation data of SPP and TP reported in Japan 11) and applied for WIfI ischemic grading (Table 1

-2-2).
The lesion was considered infected when it showed two or more of the following findings: local swelling or induration, erythema >0.5 cm around the ulcer, local tenderness or pain, local warmth, and purulent discharge (thick, opaque to white, or sanguineous secretion).In addition, local infections involving only the skin and the subcutaneous tissue, and those involving structures deeper than the skin and subcutaneous tissues, were registered separately.Local infections involving only the skin and the subcutaneous tissue were differentiated based on the size of the erythema around the ulcer, ≦2 or >2 cm.
Systemic inflammatory response syndrome, indicating systemic infection, was manifested by two or more of the following signs: temperature >38°C or <36°C, heart rate >90 beats/min, respiratory rate >20 breaths/min or PaCO 2 <32 mmHg, or white blood cell count >12,000 or <4,000 cu/mm or 10% immature (band) forms.The arteries in the ankle joint region were classified as foot arteries.
The problems and considerations on these spreadsheets are described below.In Table 3-3, the total number of limbs in the TASC II classification differed compared with the number in each column of the site of occlusion.In the "aortoiliac" lesion, a decreased number of that in the TASC II classification may have been due to input omission.In the "femoropopliteal" lesion, an increased number of that in the TASC II classification may have been due to including the crural lesions.
In Table 3-6, there was some dissociation between the R and Wound grades.This may be because of the R gradeʼs obscure definition.For example, extensive gangrene involving the forefoot is classified in R5 and W3, whereas a shallow ulcer without exposure of the distal leg bone is classified in R6 and W1.
In Table 3-6, 97 limbs (93 limbs) were registered as Ischemic grade 0 in the WIfI classification.By definition, a limb with Ischemic grade 0 has a TP of 60 mmHg or more (SPP 56 mmHg or more in the JCLIMB) or AP higher than 100 mmHg, or if arterial calcification precludes reliable AP or TP measurements, TcPO 2 60 mmHg or more (Table 1

-1-2).
There should be no limb with Ischemic grade 0 since CLI registered in the JCLIMB is defined according to the TASC II classification.The limbs might be clinically judged to be CLI irrespective of the objective ischemic index, although details are unknown.
In Table 3-6, there were 21 limbs (20 limbs) in which infection was confirmed in R4 limbs, despite the absence of a local wound by definition of R4.This may occur because tissue loss is not always requisite for fI grade.
In Table 3-6, because ischemic grade data were registered in only 893 limbs (864 limbs) among 1,145 limbs (1,105 limbs), the WIfI classification could be implemented for these 893 limbs (864 limbs).The limbs clinically judged to be CLI could be registered without their objective ischemic index.
(3) Treatment Tables 4-1 to 4-6 show the CLI treatment data.Revascularizations of the affected limbs were performed in 96% (96%) of the registered limbs, and primary major amputations were performed in 1.7% (1.5%) of the registered limbs.Among the surgical reconstruction procedures, distal bypass accounted for 50% (49%).Endovascular treatment (EVT), including EVT alone and hybrid treatment with surgical reconstruction, accounted for 55% (55%) of the total revascularization procedures.EVT applied to the crural or foot artery accounted for 40% (40%) of the total EVT.
The problems and considerations on these spreadsheets are described below.In Table 4-1, the sum of the number of cells in treatment is larger than the sum of the number of registered limbs, 1,145 (1,105), because more than one treatment method can be selected.In Table 4-1, the discrepancy in the number of major amputation to the number of detail of amputation was caused by "unused."In the column of "vein usage" in Table 4-3, how the autologous veins were used was described when they were selected as vascular conduits.The sum of the number in the column of vein usage, "in-situ," "non-reversed," "reversed," and "spliced," is larger than the sum of the number in the column of vein in vascular prosthesis.It could be because of selecting multiple vein usage for arterial reconstruction in a limb.Two veins were used in 10 limbs.Vascular prosthesis (−) included an endarterectomy without a patch angioplasty.In Table 4-4, the sum of the number of proximal anastomosis is not equal to the sum of the number of distal anastomosis.This was because multiple arteries could be selected in each anastomosis.The sum of the number of distal (crural/foot) bypass in Table 4-6 summarizes the vascular grafts used for infrainguinal arterial reconstruction.For example, the total number of vascular graft in the column of femoralproximal popliteal artery bypass was 72 (71), which was higher than 66 (65), the number of actual applications in Table 4-2.This was because multiple graft materials could be selected when multiple procedures, such as a bypass procedure and thromboendarterectomy (TEA), can be performed simultaneously for arterial reconstruction in a lower limb.When TEA without patch angioplasty was performed, "unused" was selected.

(4) Outcomes of early (1 month) after treatment
Tables 5-1 to 5-8 show the outcomes of early (1 month) after treatment.At the time of summary count at the end of March 2019, follow-up data 1 month after treatment were obtained in 993 limbs (87%), including 956 limbs (87%) with ASO.Data were collected according to the severity of the local limb conditions (Rutherford classification) and treatment measures (EVT alone or surgical reconstruction with/without EVT).The mortality rate was 2.3% (2.3%) in the whole series, and the mortality rates were 2.8% (2.8%) and 1.7% (1.5%) treated by EVT alone and by surgical reconstruction with/without EVT, respectively.The most common cause of death was cardiac disease, which accounted for 22% (23%) of all deaths.Postoperative complications were cardiac disease in 3.4% (3.5%), cerebrovascular disease in 1.3% (1.3%), pneumonia in 1.7% (1.7%), and wound complication in 4.3% (4.3%).Complications at the puncture site were noted in 1.9% (2.0%) of the limbs treated by EVT alone.
The problems, comments, and considerations on these spreadsheets are described below.The number of "bypass graft/EVT condition," "clinical limb symptoms," "ischemic wound," and "ambulatory function at discharge" did not match (Table 5-5).The total number of "ambulatory function at discharge" was 993 (956), which was equal to the number of life prognoses (Table 5-1), indicating no "unused."The number of "bypass graft/EVT condition" was not equal to the number of "ambulatory function at discharge" because the objectives of "bypass graft/EVT condition" were the limbs of survivors with arterial reconstruction and because more than one condition could be selected.The number of "clinical symptoms of limb" and "ischemic wound" was not identical.They must be identical because their objectives were survivor without major amputations.This is speculated to be due to the presence of "unused."The discrepancy in the total number of "life prognosis," "clinical limb symptom," and "amputation" is due to the difference of condition for aggregation of data.In Table 5-3, the registration of complication at the puncture site in non-reconstruction appears to be odd.The registration of complication at the puncture site was required in the limbs where PTA/STENT was selected in the revascularization method.Since multiple treatment methods can be selected, complications at the puncture site was registered in non-reconstruction and surgical reconstruction.
The number of the limbs of survivors with EVT was 459 (448 limbs) (Table 5-1), which was 13 (13) limbs less than the sum of the number in the column of minor reintervention or major reintervention in the row of the limbs with EVT; 472 limbs (461 limbs) (Table 5-6).The number of the limbs of survivors with surgical reconstruction was 471 (449 limbs) (Table 5-1), which was 5 (5) limbs less than the sum of the number in the column of minor reintervention or major reintervention in the row of the limbs with surgical reconstruction; 476 limbs (454 limbs) (Table 5-6).This is speculated to be due to death after reintervention.In Table 5-6, the objective for input of "revision for those excluding good bypass graft/EVT condition" is the limb registered in stenosis, occlusion, deterioration, anastomosis disruption (aneurysm), infection, and others of "bypass graft/EVT condition."The total number of "the contralateral limb occlusive lesions" in Table 5

-7 is equal
The Japanese Society for Vascular Surgery JCLIMB Committee, NCD JCLIMB Analytical Team to that of "life prognosis" in Table 5-1.The information of the contralateral limb at death was registered in a dead case.The sum of the number of "treatment for contralateral limb" is less than that of "the contralateral limb occlusive lesions" because the objectives of "treatment for contralateral limb" excluded the limbs of (−) in "the contralateral limb occlusive lesions."Since multiple registrations were possible, the sum of the number of "treatment for contralateral limb" was more than that of (−) in "the contralateral limb occlusive lesions."When a patient died within 1 month, the information of "newly diagnosed malignant neoplasm" at death was registered in Table 5-8.
In addition to the above, there were some parts where the total number does not match in Tables 5-1 to 5-8.It might be because several items had multiple choices or missing values.

Conclusion
Vascular surgeonsʼ contribution in participating facilities registered a sufficient amount of detailed data during busy clinical practice, which has been gradually clarifying the current status of CLI treatment in Japan.Data on CLI in 2018 were clarified, after annual data in 2013-2017.The JCLIMB Committee is planning to continue publishing an annual report in the future.In 2017, the new concept, "chronic limb threatening ischemia," was proposed instead of CLI, 13) and a new clinical guideline, the Global Vascular Guideline, was published instead of TASC in 2019. 14)he JCLIMB Committee ought to revise the survey items according to the Global Vascular Guideline, and a new registration form, which can be used in 2021, is being prepared.
The JCLIMB Committee expects that these study results will be fed back to clinical situations to help develop medical care for CLI and clinical studies using these data are ongoing.Facilities can participate in the JCLIMB at any time by contacting the JSVS secretariat for details.

Participant Facilities (84 Facilities in the Order of the Japanese Syllabary by Prefecture, Corporate Names are Omitted as a Rule)
Involving only the skin and the subcutaneous tissue (Erythema around the ulcer; 0.5-2 cm) Involving only the skin and the subcutaneous tissue (Erythema around the ulcer; >2 cm), or involving structures deeper than skin and subcutaneous tissues (e.g., abscess, osteomyelitis, septic arthritis, fasciitis) The Japanese Society for Vascular Surgery JCLIMB Committee, NCD JCLIMB Analytical Team The Japanese Society for Vascular Surgery JCLIMB Committee, NCD JCLIMB Analytical Team  The Japanese Society for Vascular Surgery JCLIMB Committee, NCD JCLIMB Analytical Team

*2)
Local infection at skin and subcutaneous tissue was classified by the spreading of erythema (≦2.0 cm or >2 cm) around the ulcer/gangrene.

*4)
The signs of SIRS are manifested by two or more of the following: ①Temperature >38 or <36°C, ②Heart rate >90 beats/min, ③Respiratory rate >20 breaths/min or PaCO  The Japanese Society for Vascular Surgery JCLIMB Committee, NCD JCLIMB Analytical Team   The Japanese Society for Vascular Surgery JCLIMB Committee, NCD JCLIMB Analytical Team      The Japanese Society for Vascular Surgery JCLIMB Committee, NCD JCLIMB Analytical Team

GI: gastrointestinal
The Japanese Society for Vascular Surgery JCLIMB Committee, NCD JCLIMB Analytical Team   The Japanese Society for Vascular Surgery JCLIMB Committee, NCD JCLIMB Analytical Team  The Japanese Society for Vascular Surgery JCLIMB Committee, NCD JCLIMB Analytical Team

Table 4 -2 is
not equal to the sum of the number of distal anastomosis in

Table 4 -4. This
was because multiple anastomosis sites could be selected in distal bypass in

Table 1 -1-2 Ischemia
ABI: ankle brachial (pressure) index, PVR: pulse volume recording, SPP: skin perfusion pressure, TP: toe pressure, TcPO 2 : transcutaneous oximetry Patients with diabetes should have TP measurements.If arterial calcification precludes reliable ABI or TP measurements, ischemia should be documented by TcPO 2 , SPP, PVR.If TP and ABI measurements result or in different grades, TP will be the primary determinant of ischemia grade.Flat or minimally pulsatile forefoot PVR= grade 3.

Table 1 -1-3 Foot infection
* SVS adaptation of Infectious Diseases Society of America (IDSA) and International Working Group on the Diabetic Foot (IWGDF) perfusion, extent/size, PACO 2 : Partial pressure of arterial carbon dioxide, SIRS: systemic inflammatory response syndrome.An Ischemia may complicate and increase the severity of any infection.Systemic infection may sometimes manifest with other clinical findings, such as hypo-tension, confusion, vomiting, or evidence of metabolic disturbances, such as acidosis, severe hyperglycemia, newonset azotemia.Table 1-2 SVS WIfI classification: Correlation of WIfI and items in JCLIMB

Table 2 - 4
Patients background 4 *including palliative therapy or recurrence

Table 2 -
I: superficial, not involving tendon, capsule, or bone, II: penetrating to tendon/capsule, III: penetrating to bone or joint)

Table 5
Outcomes early (one month) after treatment therapeutic measures: EVT (only EVT without surgical reconstruction), Surgical reconstruciton (surgical reconstruction with or without EVT)

Table 5 - 1
Life prognosis/causes of death

Table 5 - 5
Condition of the limbs