2018/11/13  · circulation 2007; 116: 2544-2552 ,7=@; a56>82:@9

51
2018/11/13 !"# PYG6

Upload: others

Post on 03-Aug-2020

3 views

Category:

Documents


0 download

TRANSCRIPT

Page 1: 2018/11/13  · Circulation 2007; 116: 2544-2552 ,7=@; A56>82:@9

�������������� �

2018/11/13�!"�# ���� �����

PYG6����

Page 2: 2018/11/13  · Circulation 2007; 116: 2544-2552 ,7=@; A56>82:@9

����

N Engl J Med 2018; 379: 1224-33.

�������������������6%���� !#"$� �

Page 3: 2018/11/13  · Circulation 2007; 116: 2544-2552 ,7=@; A56>82:@9

*�

• 76#(�• ��$`� �<�-!�=CKD=

COPD• EF40%=severe ASO�����*�>���%+�=. OCAGL3�)�Y4S=AVR_CABG�2>

�'=����1LHb7.9LFH>51&61YFH�D@@LFUACa

61O;�PHb@EJY,�NGXQ@@LGCa

�3LP�18D�E="1T9�:NZI>3�ICUR��>1�P��FKBW=[\^]CVO�1P�EM@>��NCOPD?W=7/P�0>

Page 4: 2018/11/13  · Circulation 2007; 116: 2544-2552 ,7=@; A56>82:@9

Background

Page 5: 2018/11/13  · Circulation 2007; 116: 2544-2552 ,7=@; A56>82:@9

��&���-��%40��-��(6!7�1'"��,�89;:<7���-3)5'+#6��

�� 2)/�� .��&��%40��89;:<-!7�$6��

����&89;:<-�$6!- (62*.��

Page 6: 2018/11/13  · Circulation 2007; 116: 2544-2552 ,7=@; A56>82:@9

��&���-��%40��-��(6!7�1'"��,�89;:<7���-3)5'+#6��

�� 2)/�� .��&��%40��89;:<-!7�$6��

����&89;:<-�$6!- (62*.��

Page 7: 2018/11/13  · Circulation 2007; 116: 2544-2552 ,7=@; A56>82:@9

Circulation 2008; 117: 478-84.

P 18���>���$C��9:�&�(�#

I (�,'"RHb<12.5g/dLSØ Hb<9.5g/dL?0�

C (�1,'"

O 4Primary outcome5/���3%�3AKI>)

ENJ7���/>��*GOQM !

(�,'"?Primary outcome8��=27;:

Rodds ratio, 1.8; 95% CI, 1.2 to 2.7ST� .PHILDKF��6B@

propensity-score matchingR-'C�AS<+��

Page 8: 2018/11/13  · Circulation 2007; 116: 2544-2552 ,7=@; A56>82:@9

• �������$#"���������� !������� ����!�����!�

Can J Anaesth 2013; 60: 168-75.

Page 9: 2018/11/13  · Circulation 2007; 116: 2544-2552 ,7=@; A56>82:@9

��&���-��%40��-��(6!7�1'"��,�89;:<7���-3)5'+#6��

�� 2)/�� .��&��%40��89;:<-!7�$6��

����&89;:<-�$6!- (62*.��

Page 10: 2018/11/13  · Circulation 2007; 116: 2544-2552 ,7=@; A56>82:@9

Circulation 2007; 116: 2544-2552

��,7=@;��A56>82:@9<@8B

��A���)���)�$�BAadjusted odds ratio, 3.38; 95% CI, 2.60 to 4.40B#$5<?;A����) ��)!'�BAadjusted odds ratio, 3.35; 95% CI, 2.68 to 4.35B

031&$�/��1 �

P �"�%4�-.16���2��

I %�&$�C %�(&$�

O *Primary outcome+��A���)���)�$�B#$5<?;A����) ��)!'�B

Page 11: 2018/11/13  · Circulation 2007; 116: 2544-2552 ,7=@; A56>82:@9

Circulation 2007; 116: 2544-2552

�Secondary outcome����%�������4.25&�30���%adjusted odds ratio, 6.69; 95% CI, 3.66 to 15.1; P<0.0001&31��1%adjusted odds ratio, 2.59; 95% CI, 1.68 to 4.18; P<0.0001&>1%adjusted odds ratio, 1.32; 95% CI, 1.08 to 1.64; P=0.003&

→ �����$"���� #!������!����

Page 12: 2018/11/13  · Circulation 2007; 116: 2544-2552 ,7=@; A56>82:@9

N Engl J Med 2011; 365: 2453-62.

P �)$!�@��D0 FC;50���<3�'22�+�3���?Hb<10g/dL=>:9�&

I -)�/%NHb<8g/dLOC -)1�/%NHb<10g/dLOO ��3��>8?.�@�*6<7>4

GKLHMHJI47�,@��,RCT31"��

30�5EB60��� =C?���>8

FOCUS

1�(�+@RCT<A#��� ?���>8

Page 13: 2018/11/13  · Circulation 2007; 116: 2544-2552 ,7=@; A56>82:@9

P �$���6� 9�*��:8150���2-",,�%�3���5Hb<10g/dL340/�!

I '$�) BHb<8g/dLC

C '$+�) BHb<10g/dLC

O (����

;?@<A<>=47�&6�&RCT-+��� Lancet 2015; 385: 1183-89.

FOCUS

(����8���4.

(hazard ratio, 1.04; 95% CI, 0.91 to 1.20; P=0.56C

+�#�%6RCT27���������4.

Page 14: 2018/11/13  · Circulation 2007; 116: 2544-2552 ,7=@; A56>82:@9

PSXT17K�6�. ;A� ;RCTA@,&�

N Engl J Med 2015; 372: 977-1008.

=9�?2I@�?2H"��JF[odds ratio, 1.11; 95% CI, 0.91 to 1.34; P=0.30\

�6�:�K<9*=9�?LA=9�� ��N�DA-#7�OQURWL@�

P @1�K�6�:N�EG16'��HA:�Hb<9g/dL or Hct<27%K�3

I =9�?2[Hb<7.5g/dL or Hct<22%\

C =9@�?2[Hb<9.0g/dL or Hct<27%\

O BPrimary outcomeC)�(��3Z!��K�$[�9+A>�$\MGL89PVYU[4��A�/%�A5089AAKI\K��

TITRe2

Page 15: 2018/11/13  · Circulation 2007; 116: 2544-2552 ,7=@; A56>82:@9

N Engl J Med 2015; 372: 977-1008.

30�����������������90������� ���������4.2% vs. 2.6%; HR 1.64; 95% CI, 1.00 to 2.67; P=0.045�

TITRe2

���…

Page 16: 2018/11/13  · Circulation 2007; 116: 2544-2552 ,7=@; A56>82:@9

Background• ����8*'�����2��WD@8�,6��1)(.'"��#0"�%�#8�!,6TRICS� &8'+73/2 &2limitation8��,6-4' �(�$5�/��

Ø ��]����^

=JE]22^ 9SW=]8^ <\DHVW9]12^KU\C\V[I]5^ ��]2^ RY\B9]1^B[>Q\X]1^ B[>Q\X]1^ :[I]2^G[R\@]1^ I:F]2^ D:D]2^DP:[]4^ ?WBT]1^ X\RK9]1^;COH]1^ ;COH]1^ :DV;X]2^NVCX]1^ AZ[L9]5^ �9MW=]1^

Page 17: 2018/11/13  · Circulation 2007; 116: 2544-2552 ,7=@; A56>82:@9

�B,FC-% FRCTFC��;E N Engl J Med 2017; 377: 2133-44.

8�28�?QVprimary outcomeT ��SM

_11.4% vs. 12.5%, odds ratio, 0.90;95% CI, 0.76 to 1.07`

→TITRe2;ERD�MP0"

P ���3Z(MP�6�8Z�LX�.���U'�]\[Z NX18&��U�2

I <7���_Hb<7.5g/dL8�^8�`C <7C�@1_Hb < 9.5g/dL8�^8�ICUa

Hb < 8.5g/dL8�CICU)$`O GPrimary outcomeH8�28�IXJV=AWQ_JOY�J�`UF'�F�/#�F4��F>!Z�K�:+*5�U9�outcome

TRICS�

Page 18: 2018/11/13  · Circulation 2007; 116: 2544-2552 ,7=@; A56>82:@9

��&��&��

�����% �$������'���) �#(!0

TRICS���% "(6/�&�*+-,.)��

Page 19: 2018/11/13  · Circulation 2007; 116: 2544-2552 ,7=@; A56>82:@9

����

N Engl J Med 2018; 379: 1224-33.

�������������������6%���� !#"$� �

Page 20: 2018/11/13  · Circulation 2007; 116: 2544-2552 ,7=@; A56>82:@9

Methods

Page 21: 2018/11/13  · Circulation 2007; 116: 2544-2552 ,7=@; A56>82:@9

Study design

• ���• ��4��primary outcome��,��5• ���!• �)+���+IRB*����%.)#-"• ��&'1302 ������$�!��/�('"

Page 22: 2018/11/13  · Circulation 2007; 116: 2544-2552 ,7=@; A56>82:@9

PICOPatient �.�1C�?B�&���HEuroSCORE�≧6I

A"�FEDC�@B��H18!��AI�*Intervention 6/���KHb < 7.5g/dL H1�;1�IComparison 6/: 8)KHb < 9.5g/dL H1�;1�ICUI

Hb < 8.5g/dL H1�:ICU# IOutcome <Primary outcome>

1�6G��A;"�;�'��;,��;7�C�>�4%$-�A2�outcome

<Secondary outcome=• Expanded secondary composite outcome: Primary outcomeJ1�6G��AER�5;��9;��+/0��1A2�outcome• composite outcomeA�3(H1�6G��I

Page 23: 2018/11/13  · Circulation 2007; 116: 2544-2552 ,7=@; A56>82:@9

Inclusion criteria• 18,��• ��!@b4WY!E'Gb�U`��• G�EuroSCORE�≧6• �%T _aZS`

Ø EuroSCORE�scale 0�47[fecTPS<R!E'G�^-�gfdTPSV\b:�X`O8h

�QR#�RCOPDR!E� C5$R;>�7+BN�RL!G(�RF/CrR. #!D0RK6]G�1&R���3!6R��+BR)I^!=*�R@PF�6R?"RCABG�2��RAJ� C'GR*���M9H

Eur J Cardiothorac Surg 1999; 16: 9-13.

Page 24: 2018/11/13  · Circulation 2007; 116: 2544-2552 ,7=@; A56>82:@9

Exclusion criteria• "�$�5(24-'��• "�$�5��)*��• !�"#�89?:=6<;.��),'*��• ���5(3��• VAD��/*1+(/�#5(3��• ��%���/��@��� �/&3 �0<>7;�/�.�����5(3A

Page 25: 2018/11/13  · Circulation 2007; 116: 2544-2552 ,7=@; A56>82:@9

InterventionIntervention? Control?

strategy KD�S KDU�S

JD7KDR� Hb < 7.5g/dL |F�VF%} Hb < 9.5g/dL |F�VF%ICU}Hb < 8.5g/dL |F%UICU;3}

Hb6� !dZcjVF�V�"'A�9�{�{%VICU#�1V1, 2, 3, 5, 7, 9, 11/<

KD-5 1��fJD7p,�[VHb�I R��fHb6�1YmKDhbf1Q�S

F�~21QICU~181Q�|step-down unit=HCUp�i}�C;3~401Q

KDvytsx�1�4H�

(Md�D1V�Deln&8�)���1→4DO+%=_eVWnXg�4%241Q�e�P

]fKD rquwqzk.G*@e�`XaVNE�f�Dk��:$e [a,��B

��>�2Q F%28/h^gLTfX\oY0X-

Page 26: 2018/11/13  · Circulation 2007; 116: 2544-2552 ,7=@; A56>82:@9

Statistical analysis• ARHOA>DV���85%T.�KSBR3%845�U���,1:primary outcome9�46:ARHOA>D+

• Per-protocol*�• .�KSBRV��,18�:3%T0.025��αPJOU• -�Odds�;��:/$7-�V�23��3&�#3�):%03��:'"�3?P=EFR?N=MRC3IL@QGR3���(

• ��VKaplan-Meier curves3log-rank test7� • *�;R statistical package version 3.4.3<�!

Page 27: 2018/11/13  · Circulation 2007; 116: 2544-2552 ,7=@; A56>82:@9

• ����� ��• ���• ��������• ���

Subgroup analyses

Page 28: 2018/11/13  · Circulation 2007; 116: 2544-2552 ,7=@; A56>82:@9

Results

Page 29: 2018/11/13  · Circulation 2007; 116: 2544-2552 ,7=@; A56>82:@9

5243�19��74�������

per-protocol�4860�

�� �2430��

modified ITT�5092�

6���Primary outcome

96%

Page 30: 2018/11/13  · Circulation 2007; 116: 2544-2552 ,7=@; A56>82:@9

��

����� vs.������• �� $��� �• ��� 72�• EuroSCORE�7.9 vs. 7.8• ��Hb 13.1 vs. 13.1g/dL• ���Hb 9.4 vs. 10.2g/dL• ����CABG!# 25.6% vs. 26.5%Valve!# 28.9% vs. 29.5%CABG+valve 19.1% vs. 19.4%

���Hb"����������

Page 31: 2018/11/13  · Circulation 2007; 116: 2544-2552 ,7=@; A56>82:@9

����

����� vs.������

• ����� 52.3% vs. 72.6%

• �����$����$��%��"

���� 23.5% vs. 27.1%����� 28.8% vs. 29.5%

�����!%���� �"�"&���'��#��

Page 32: 2018/11/13  · Circulation 2007; 116: 2544-2552 ,7=@; A56>82:@9

Primary outcomes

• !�#�($#�*�� )'402/2317�.17.4%/ vs. 402/2347�.17.4%/.Odds Ratio, 1.02; 95% CI, 0.87 to 1.18/

<Primary outcome>��6-���+%���%����%��%"�,�&� �����+��outcome

Page 33: 2018/11/13  · Circulation 2007; 116: 2544-2552 ,7=@; A56>82:@9

Secondary outcomes

• ���� �����

���141/2291��6.2%�vs. ��149/2318��6.4%��Odds Ratio, 0.95; 95% CI, 0.75 to 1.21�

Page 34: 2018/11/13  · Circulation 2007; 116: 2544-2552 ,7=@; A56>82:@9

• ����� ����"���!�1015/2318�%43.8%& vs. 1006/2348�%42.8%&%Odds Ratio, 1.04; 95% CI, 0.93 to 1.17&

Secondary outcomes�Expanded secondary composite outcome�Primary outcome'� 6$���#ER��������������#�outcome

Page 35: 2018/11/13  · Circulation 2007; 116: 2544-2552 ,7=@; A56>82:@9

Subgroup analyses of the primary outcome

• 75����������

����� ��

• 75���������

����� ��

Page 36: 2018/11/13  · Circulation 2007; 116: 2544-2552 ,7=@; A56>82:@9

Sensitivity analyses of the primary outcome

��4'�46;7����05)����1��-9��+�8:.A• "�>@=<?3�-970%��4# • 80%��4# • 100%4# • >@=<?��;,.��4&�• ���%28�$0!��"�;,2*/.��• (�3Hb<9.5g/dl3282*/.��

Page 37: 2018/11/13  · Circulation 2007; 116: 2544-2552 ,7=@; A56>82:@9

Discussion

Page 38: 2018/11/13  · Circulation 2007; 116: 2544-2552 ,7=@; A56>82:@9

Finding• TRICS�;EX6g c_fh^bdTYF�4�7�W�+���X%�ea`]!P\�0WLISF<5(>5�A/YD�A/U&=OSF�%�F�,#�F25-C�F?"]�J�9*)3��M[V\primary compositeoutcomeND �THRQG

• 6g �'TFprimary composite outcomeW�KF�BFER�:F�156�7]�Zexpanded composite outcomeX�$�8.WLISF>5�A/UD�A/UX@W!��YVMRQG

Page 39: 2018/11/13  · Circulation 2007; 116: 2544-2552 ,7=@; A56>82:@9

H?a@�#�noqpr• H?aK?dS\lg@�d1$TifN$#��FcO�Z_Sk�<�V !Yl_SkR

• H?D0�d79M6�8d)�eQ�M6G>m�WJXZQ#�bnoqprm N[k�<�V3�Yl_SkR

PLoS One 2017; 12: e0180165.Am Heart J 2017; 185: 140-9.

Circulation 2008; 117: 478-84.J Thorac Cardiovasc Surg 2012; 144: 654-662.

Ann Thorac Surg 2013; 96: 478-85.Ann Thorac Surg 2003; 76: 784-92.

Circulation 2007; 116: 471-9.Can J Anaesth 2015; 62: 377-84.

• C�24eI?,K?aQ@�10��d(�+s�B.�:�+d��adOLm3Z_SkR

Ann Thorac Surg 2012; 94: 460-7.Ann Thorac Surg 2002; 74: 1180-6.Ann Thorac Surg 2006; 81: 1650-7.

Circulation 2007; 116: 2544-52.

• ��aZ_QK?d-E5��%ci^_Q-��a*/D0�%d�;mg]jZQ�&h=�P�m�WJX[�<�V3�Yl_SkR

Transfusion 2018; 58: 804-15.`eQK?cikH?dA'Vnoqprm"�[kUt

Page 40: 2018/11/13  · Circulation 2007; 116: 2544-2552 ,7=@; A56>82:@9

P � �#=/318���7��

I #��$�"+:C #��$�"51O #�30����

?AD>��%��.@CEB��Ann Thorac Surg 2013; 96: 478-85.

�$�"!�-#���7(��4+;Fodds ratio, 3.45; 95% CI, 2.78 to 4.28G

1,1*27��5�)8&"�'"69: �0<;

Page 41: 2018/11/13  · Circulation 2007; 116: 2544-2552 ,7=@; A56>82:@9

• D<[G<^OWfa=�^."Pc`J"!��B]K�UZOe�9�Q� TfZOeN

• D<@-�^46I3�5^&�_M�I3C;g�RFSUM!�\hikjlg JVe�9�Q0�TfZOeN

PLoS One 2017; 12: e0180165.Am Heart J 2017; 185: 140-9.

Circulation 2008; 117: 478-84.J Thorac Cardiovasc Surg 2012; 144: 654-662.

Ann Thorac Surg 2013; 96: 478-85.Ann Thorac Surg 2003; 76: 784-92.

Circulation 2007; 116: 471-9.Can J Anaesth 2015; 62: 377-84.

• ?�/1_E<)G<[M=�10��^%�(m�>+�7�(^��[^KHg0UZRXN

Ann Thorac Surg 2012; 94: 460-7.Ann Thorac Surg 2002; 74: 1180-6.Ann Thorac Surg 2006; 81: 1650-7.

Circulation 2007; 116: 2544-52.

• ��[UZMG<^*A2��#]cYZM*��[',@-�#^�8gaXdUM�$b:�L�g�RFSV�9�Q0�TfZOeN

Transfusion 2018; 58: 804-15.

D</G<[=�!�hikjl

Page 42: 2018/11/13  · Circulation 2007; 116: 2544-2552 ,7=@; A56>82:@9

1/D�5

• �-�0�G�5#H�G&(D�.@C;A:Ann Thorac Surg 2014; 98: 1274-80.

Transfusion 2013; 53: 1688-97.

• �5G�"��FH�89��3��*$�9�;'�)!% �9�5�4G�290���90�,�9�� +6�>�ILK:

Transfusion 2013; 53: 1688-97.J Thorac Cardiovasc Surg 2001; 122: 278-86.J Thorac Cardiovasc Surg 2014; 147: 1013-8.

• �5F<?K1/G�7H�J=DEBC;E;:

Page 43: 2018/11/13  · Circulation 2007; 116: 2544-2552 ,7=@; A56>82:@9

30���5���Godds ratio, 1.01; 95% CI, 0.45 to 2.25; P=0.991H30���5��%Godds ratio, 0.92; 95% CI, 0.78 to 1.08; P=0.313H1 ���GHR, 0.87; 95% CI, 0.65 to 1.16; P=0.344H(.<:"%��Hb2&��

→!�3��%E���35$#�6 94*0/

CAM

ULAT

IVE

SURV

IVAL

J Thorac Cardiovasc Surg 2015; 150: 1322-8

P ���585��=,'��-1"%-/��GN=1044H

I "%�Hb≦8g/dLGn=153HC "%�Hb>8g/dLGn=891HO 30���5���);7��%'1 ���

>CD?��'��+@BFA��

Page 44: 2018/11/13  · Circulation 2007; 116: 2544-2552 ,7=@; A56>82:@9

• ����� ��������!����������� �������

������

Page 45: 2018/11/13  · Circulation 2007; 116: 2544-2552 ,7=@; A56>82:@9

�%�

• "�$� ERCT7IG[TNW\RSAF3+#�0F1�0B�*=@��NOVQZD���9C6;BM�=@6K93-���D/=@F��DF(�<L@6C8?>4

• �� HAF3RCTD7:K�-XP]^NUY�.FTITRe2'2E90�A5?>4

• TRICS�'2FTITRe2'2E�!�2���3,)�.2�A5J3�� F$�+#��E-�NOVQZD/=@3+#�0E1��M&�=>4

Page 46: 2018/11/13  · Circulation 2007; 116: 2544-2552 ,7=@; A56>82:@9

N Engl J Med 2017; 377: 2133-44.

28 "4��9:>;?D���$5��9:>;?4@=<��375���05# ,2).- Bodds ratio, 1.17; 95% CI, 0.91 to 1.50C75���05# ,/(- Bodds ratio, 0.70; 95% CI, 0.54 to 0.89C

6A�"4!�9:>;?D75���05��%�$�0@=<*�).-75���05���$�0@=<*�).-

���

&'��3,/+��*�876��4��1��

TRICS�

Page 47: 2018/11/13  · Circulation 2007; 116: 2544-2552 ,7=@; A56>82:@9

:.A�X�F[@RV

���0XQed$&5D

• EF�*]:.@=�� r�>7-G�"G����"sf�3WOZJGIdJ]G:.b8.[cd��C[LJV�F@=�\ !NIdX\�4f'VdPXNWOdH

• ghmio[�Td�F[�SU:.\�C\ !\+�XZdpinlo]G�,�/�*f�6XRV���2Td�0NIdH

• �$&\#1]G�/�:.\$&[?�<9f(_;`�)f%RVJdH

• :.A�N�F[�SV!Zd^OMYKM]G8.[�TdqkjNEJB[LJVa�2Qed�0NIdH

Page 48: 2018/11/13  · Circulation 2007; 116: 2544-2552 ,7=@; A56>82:@9

Limitations• !25hm28��UsVmHM�R<��kF?���|��uJ�_bs�@mj\Rcl�l��{���+�oF?kX]s�.u��as^iZh[jYedS

• vx�z����mODI7R/MBKR�������~���un%Tj� )Yq�qtdS�y��v��*tZR,�l(08k�sim9Wk\VZRV\fYl�y��v��Z&>`d;�mUsS_qkR'�l,�m�;hUedS

• Primary outcome���m�:l96%h�-;hUedS&>`d���l�\mpilot studyl�:kUrRpilot studyhmL GEm25�}w�h,�_tgVjYedS

• P1$�kps�wv�l;�mN�h[jVZR%Tj���"kps6#mR��A"l6#i�=`gXrR!CQ6#l3��Z4�_tsS

Page 49: 2018/11/13  · Circulation 2007; 116: 2544-2552 ,7=@; A56>82:@9

Conclusions��<[ZQ�?*I�"@I.-�AHW6'I

�: =\�NY�4���W+�_^]\$PY���7V�PYI

F3C;E�/cHb < 7.5g/dL a=�I=�bXI�%3C;E�/cHb < 9.5g/dL a=�I=�ICUb

Hb < 8.5g/dL a=�GICU0)bU,BOSI

=�6`#��W�+�I�5(�I8��ID&\�L!?219��W>�outcomeMG��TKRQJ

Page 50: 2018/11/13  · Circulation 2007; 116: 2544-2552 ,7=@; A56>82:@9

�% �.BHD8?N:

• RCTFA*�QRTSVG0��;&�=O3�.BJ# ("F97A("�-;�I>74

• 75���G� F?N("��F+>AJ3��/BH("�-BK7@P84

• ("��F9<N2G$�H� G��'1CEN4

• (",�G��KMJ3�5GHb��GXUW:LG��;)$B6N�!�;6N4

Page 51: 2018/11/13  · Circulation 2007; 116: 2544-2552 ,7=@; A56>82:@9

4�

• 76,2�• %�-r��H�7)�ICKDI

COPD• EF40%Isevere AS\�����4�J���.5�I8(\CAGY3'3�h?aIAVRqCABG$<J

�1I��&";YHb7.9YRTJ@;0A;hRT#PLLYRdMOs

A;\G�]HbLQWh6�[Sg^LLYSOs

!=Y]�;DP�QI+;bE&F[ iUJ=�ICU_��J;�]��RXNfIkmpoOe\�;]�QZLJ%�[COPDKfIC9�]�:J

ljnp\";YIHb7.5h��g^A;R`RdMJTURIkmpoOe\�;P�/[�RTfI

;<� P���[ZVT��]IBcOZA;h*>R`RdMJ