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Acquired immunodeficiency syndrome, a complication of cardiothoracic surgery
J THORAC CARDIOVASC SURG 1989;97:126-9
Acquired immunodeficiency syndrome, a complication of cardiothoracic surgery We identified 13 patients who contracted acquired immunodeficiency syndrome or human immunodeficiency virus--related disease after a cardiothoracic operation. The operati~ were perfonJJect between January 1981 and November 1984, and the diagnosis of human immunodeficiency virus--related disease was established from 26 to 54 months after operation. The survival time from diagnosis ranged from 8 days to 14 months in the 10 patients who have died. A clinical iDness developed in three of the patients immediately postoperatively that was consistent with primary human imniunodeficiency vims mononucleosis. The clinical features included a widevariety of opportunistic infections, but an abnormally high percentage of the patients first showed symptomsof dementiaor neoplasticdisease. In many patients, the diagnosis was not suspected for a prolonged period of time. On the basis of the prolonged incubation period, the incidence of this disease is 6kely to increase for several more years.
Mark Schiff, MD, Allan Katz, MD, Bruce Farber, MD, and Mark Kaplan, MD, Manhasset and New York, N.Y.
Acquired immunodeficiency syndrome (AIDS), described in 1981, has become an increasing public health problem in the United States and worldwide. As of this writing, 52,000 cases have been reported in this country, and the 3-year mortality rate exceeds 90%. Approximately 2% of the cases in the United States have resulted from transfusion of blood or blood products.' Since 1983, we have observed 25 cases of transfusion-related human immunodeficiency virus (HIV) infection in a cohort of 435 patients with antibody to HIV. Within this group, 13 patients acquired the disease after cardiothoracic operation. The relatively high incidence of AIDS after cardiothoracic operation seems worthy of investigation to determine whether any unusual features are present in this group. The clinical features of this illness are presented to enable physicians caring for these patients to recognize this devastating complication of cardiothoracic operation.
Methods We have attempted to detect HIV infection in hospitalized patients by serologic assay since June 1984. Initial assays were
From the Departmentof Medicine, Divisions of Pulmonary Medicine and Infectious Disease & Immunology, North Shore University Hospital, Manhasset, N.Y., and the Department of Medicine, Cornell University Medical College, New York, N.Y. Received for publication Dec. 4, 1987. Accepted for publication July 12, 1988. Address for reprints: Mark Schiff, MD, Division of Pulmonary Medicine, North Shore University Hospital, 300 Community Dr., Manhasset, NY 11030.
126
done in the Laboratory of Tumor and Cell Biology of the National Cancer Institute in conjunction with Dr. M. G. Sarngadharan and Dr. Robert C. Gallo and were later done in our own laboratory. Patients entered in this study had serologic tests performed after informed consent was obtained. Serum was stored at -20 C. This study was approved by our investigational review board. Antibody to HIV was detected with the use of standard enzyme-linked immunosorbent assays and confirmed by Western blot tests with human T-cell Iymphotrophic virus III antigen prepared by growing an HIV isolate in the H 9 cell line. Antigen was purified by sucrose density gradient centrifugation and disrupted by lysing antigen with radioimmunoprecipitation antigen buffer as previously described.' Western blot tests were done on 3 mm strips of antigen separated first in 12% Laemelli gels and then transferred to nitrocellulose eiectrophoretically. Antibody was detected after strips were soaked in serum at a dilution of 1:50. Antibody bands were visualized with the use of horseradish peroxidase conjugated goat anti-human antibody and appropriate substrate. Identification of the P21 and P41 bands was required tor diagnosis of HIV. T-cell subset tests were performed by methods previously described.' We 4 have been systematically screening patients at high risk for HIV infection since the discovery of HIV in samples contributed from our patients. All patients with clinical features of HIV infection, class IV, as defined by the Centers for Disease Control,' were tested after informed consent was obtained. Screening has been targeted particularly toward patients in the identified high-risk groups including those with a history of blood transfusion. The subjects of this report had no known risk factors other than transfusion in association with cardiac operation. 0
Results Thirteen patients had HIV infection with one or more features of AIDS after undergoing cardiothoracic oper-
Volume 97 Number 1
Development of AIDS after cardiothoracic surgery
January 1989
127
Table I Patient
Age* (yr)
Sex
I
2
54 62
M M
3 4
62 73
M
5 6 7 8 9 10
55 58 60 7
M M M
II
12 13
60
23 66 47 57
F
F F M
F M M
Date of operation
1/81 7/81 3/83 [repeat] 9/81 3/82 6/82 [repeat] 5/82 6/82 8/82 4/81 11/84 11/81 3/83 10/82 3/83
Type of operation
Date of HIV Dxt
Date of death
CABG CABG
6/83 4/84
7/84 3/85
CABG CABG
7/84 6/85
11/84 11/85
Aortic valve replacement CABG CABG Tetralogy of Fallot repair Aortic valve replacement Tetralogy of Fallot repair CABG CABG CABG
3/86 9/86 4/86 10/85 1/87 6/86 2/86 10/87 1/87
5/86 9/86 6/87 Alive Alive 10/86 2/86 Alive Alive
CABG, Coronary artery bypass grafting; Dx, diagnosis. •Age of patient at time of AIDS diagnosis. tDate at which the patient first required treatment for an opportunistic infection that confirmed the diagnosis of AIDS.
ation; 10 of these have died. The age range at the time of diagnosis was 7 to 73 years. The operations were performed between January 1981 and November 1984, all but three in 1981 and 1982. The patients exhibited manifestations of HIV infection leading to diagnosis from June 1983 to October 1987. The operations performed included coronary artery bypass grafting (11 operations in nine patients), aortic valve replacement (twopatients), and correction of tetralogy of Fallot (two patients). The diagnosis of AIDS or AIDS-related complex was established between 26 and 54 months after operation, and survival from time of diagnosis ranged from 8 days to 14 months in the 10 patients who havedied (see Table I). The clinical features of AIDS in our patients included a variety of infections. Seven patients had a single episode of Pneumocystis carinii pneumonia. Four patients had disseminated Mycobacterium avium-intracellulare isolated from blood and stool, Candida esophagitis was found in four cases, and Cryptosporidium was isolated from stool in two patients.A number of bacterial and viral infections were also seen and are detailed in Table II. A variety of neoplastic conditions occurred in our patients as well. Two patients had colon cancer, one had thyroid cancer with metastatic disease, three had lymphomas, and one had Kaposi's sarcoma. One had multiplebasal cell carcinoma of the skin. Three of these tumors occurred in a single patient (colon carcinoma, Kaposi's sarcoma, diffuse histocytic lymphoma). Five of 13 patients initially showed symptoms of progressive dementia, and dementia or other disturbances of psychomotor function developed in five more patients (see Table 11). Early signs included memory
loss, confusion, and lethargy. These findings often preceded a definite diagnosis of AIDS. The encephalopathy was rapidly progressive over 3 to 6 months. Six patients became immobile, incontinent, and essentially nonverbal by the time of final hospitalization. One patient had received psychiatric treatment for depression before the diagnosis became apparent. Several miscellaneous features of disease in our patients deserve comment. The operations were performed in 10 different hospitals, but all patients received blood from The Greater New York Blood Program. We do not have information regarding the proportion of transfusions in these institutions used to support the cardiac surgery programs. Three patients had a febrile illness documented in the postoperative period, each with atypical lymphocytes noted on peripheral smear. Serum from three spouses (of seven tested) was positive for HIV. AIDS has not developed in these three spouses, but two have lymphadenopathy and two appear to have early signs of dementia. In one of these cases, female-to-male transmission of the virus occurred. None of the spouses tested had any other known risk factor for HIV infection.
Discussion Among the cases of transfusion-related HIV infection seen in our institution, those involving cardiothoracic operations account for 40%. The relatively large number of cases we have seen relates to our proximity to New York, a metropolitan area with early and subsequently heavy prevalence of HIV -infected persons. It was therefore inevitable that this infection would affect the blood donor pool in our region. A unit of HIV-infected blood
The Journal 01 Thoracic and Cardiovascular
1 2 8 Schiff et al.
Surgery
Table II Patient
T-cell subset ratio (T4-T8) 0.3
2
0.07
3
0.4 0.1
4
0.26
5 6 7
0.26
8 9 10
0.9 0.5 0.05
ND
11
ND
12 13
0.04 0.3
Infections
Neoplasias
Candida esophagitis, herpetic stomatitis, PCP,
disseminated MAl PCP, Klebsiella, Pseudomonas, Staphylococcus aureus pneumonia, HSV, MAl, Cryptosporidium (stool) Candida esophagitis HSV, MAl, PCP Pseudomonas pneumonia, Escherichia coli sepsis, Campylobacter (stool) Candida esophagitis, Cryptosporidium, PCP PCP, herpes zoster Disseminated Mycobacterium tuberculosis Candida
Lymphadenopathy PCP PCP Chronic sinusitis Chronic diarrhea, weight loss
Dementia
Kaposi's sarcoma, DHL, colon None
Severe depression
Colon None
Severe depression dementia Severe dementia
DHL None Multiple basal cell cancers None Thyroid carcinoma Large cell lymphoma None None None
Dementia Severe dementia Severe dementia
Parkinson's disease
Psychomotor retardation None Retarded from birth Unknown Depression None
PCP, Pneumocystis carinii pneumonia; DHL, diffuse histiocytic lymphoma; HSV, herpes simplex virus; MAl, Mycobacterium avium-imracellulare; ND, not done.
has a high likelihood of transmitting infection to the recipient. Current data suggest at least 90% of persons who received such blood have become HIV antibody positive.v" Most of our cases were diagnosed after a clinical illness arose. The median latency from time of operation to diagnosiswas nearly 3 years. Most of our patients had been ill from 3 to 6 months preceding diagnosis. The disease tended to be rapidly progressive in these patients, with survival less than 1 year in all but one case. The clinicalfeatures seen in our patients have all been described in AIDS but the prevalence of central nervous system involvement and neoplasm was uniquely high,"" The opportunistic infections were similar to those described in the AIDS populationat large and included Pneumocystis carinii pneumonia, Mycobacterium infections, and Candida in many cases. There were several episodes of bacterial sepsis, pneumonia, and diarrhea consistent with depressed immunity in these patients. The T4:T8 ratio averaged 0.3 at the time of diagnosis, which indicated severe depression in helper T-cell numbers. Of note was a clinical illness in three patients immediately postoperatively consistent with HIV viremia as previously described by Ho and associates." This illness, consisting of a mononucleosis-like syndromewith fever, malaise, and lymphocytosis, may be confusing in the patient having a cardiac operation. It can be mistaken for postperfusion syndrome or postpericardiotomy syndrome. The incidence of severe progressive
dementia in many of our patients was noteworthy. This syndromeis thought to be due to direct HIV infection of brain tissue. Clinical features are those of a rapidly progressive dementia beginningwith apathy, depression, and memory lossand developing into full-blown dementia.' Although 60% to 90% of patients with AIDS have some neurologic manifestations, the presence of AIDS dementia in virtually all of our patients represents a higher percentage than that usually reported.' The presence of severe dementia at the onset of illness has been uncommon among our remaining AIDS population. We can only speculate as to the reasons for this. Postmortem studies show that neuropathic changes are present in 90% of patients dying of AIDS. 10 Because an older age group is at risk for AIDS after cardiothoracic operation, the neurologic involvement may become clinically evident earlier. Recognition of this syndrome, the earliest presenting sign in many of our patients, is important. Symptoms may otherwise be attributed to depression or Alzheimer's disease. Evaluation of these patients for other AIDS-related manifestations that may affect the central nervous system is important. None of our patients had serologic evidence of syphilis or toxoplasmosis or evidence of central nervous systemlymphoma on computed tomographic scan. We also observed a high incidence of neoplastic disease in these patients: two had coloncancer, one had thyroid cancer, one had multiple basal carcinoma, three had lymphoma, and one had Kaposi's sarcoma. Well
Volume 97 Number 1 January 1989
have previouslyreported a high incidence of solid tumors and lymphomas in patients with HIV infection in our institution. The incidence of lymphoma in patients with AIDS is known to be increased. The incidence of solid tumors in these patients may simply reflect the chance concurrence of these two diseases. Alternatively, it may be a consequence of disordered immune function. Presumably, the progressive loss of the immune function including the surveillance function allows the expression of latent tumors. The high prevalence of solid tumors and lymphomas in this small group of patients may reflect the increase in endemicity of cancer in this age group, which becomes manifest after collapse of the immune system. The advent of HIV antibody screening of banked blood will greatly reduce the threat of HIV infection in patients undergoing cardiothoracic operations in the future.' However, latency of this disease was 3 years in our patients. This implies that a large group of patients are still at risk. The number of AIDS cases has increased greatly since 1981; and the number of symptom-free infected persons is thought to be much larger. Thus the incidence of infection in the donor pool may well have been increasing up to the advent of large-scale screening in May 1985. The risk of contracting AIDS after operation might therefore be expected to peak in 1988. Alternatively, this may represent an early peak with additional cases developing with time. A recent estimate of the latency of HIV infections after transfusion is 54 months." Awareness of this problem, and early detection of cases, would be helpful in limiting further spread of the disease. We know, for example, that three spouses of seven tested among our patients have acquired the infection. This is a high proportion, in light of the significance of this disease. In addition, affected patients, once identified, might be offered azothymidine" in hopes of reducing morbidity and extending their lives. REFERENCES 1. Centers for Disease Control. Human immunodeficiency virus infection in transfusion recipients and their family members. MMWR 1987;36:137-40.
Development of AIDS after cardiothoracic surgery
129
2. Sarngadharan MG, Popovic M, Bruch L, Schurpbach J, Gallo RC. Antibodies reactive with human T-1ymphotrophic retroviruses in the serum of patients with AIDS. Science 1984;224:506-8. 3. Pahwa S, Kaplan MH, Fikrig S, et al. Spectrum of human T-cell lymphotrophic virus type III infection in children. JAMA 1986;255:2299-305. 4. Gallo RC, Salahuddin SZ, Popovic M, et al. Frequent detection and isolation of cytopathic retroviruses (HTLV 1Il) from patients with AIDS and at risk for AIDS. Science 1984;224:500-3. 5. Centers for Disease Control. Classification system for human T-lymphotrophic virus type IIljlymphadenopathy-associated virus infection. MMWR 1986;35:334-9. 6. Hove JR. Transfusion-associated hepatitis and AIDS: what is the risk. N Engl J Med 1987;317:242-5. 7. Snider WO, Simpson DM, Nielson S, Gold JWM, Metreka CE, Posner JB. Neurologic complications of acquired immunodeficiency syndrome: analysis of 50 patients. Ann Neurol 1983;14:403-18. 8. Ho DD, Pomeranz RJ, Kaplan Jc. Pathogenesis of infection with human immunodeficiency virus. N Engl J Med 1987;317:278-86. 9. Ho DD, Samgadharan MG, Resnick L, et al. Primary human T-lymphotrophic virus type III infection. Ann Intern Med 1985;103:880-3. 10. Neilson SL, Petito CK, Winachor CD, Posner JB. Subacute encephalitis in acquired immunodeficiency syndrome: a post-mortem study. Am J Clin Pathol 1984; 82:678-82. 11. Kaplan MH, Susin M, Pahwa SG, et al. Neoplastic complications of HTLV-1Il infection. Am J Med 1987;82:389-95. 12. Lui KJ, Lawrence ON, Morgan WM, et al. A mode1based approach for estimating the mean incubation period of transfusion associated acquired immunodeficiency syndrome. Proc Nat! Acad Sci USA 1986;83:3051-5. 13. Fishel MA, Richman DD, Grieco MH, et al. The efficacy of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS related complex. N Engl J Med 1987:317:185-91.
Acquired immunodeficiency syndrome, a complication of cardiothoracic surgery We identified 13 patients who contracted acquired immunodeficiency syndrome or human immunodeficiency virus--related disease after a cardiothoracic operation. The operati~ were perfonJJect between January 1981 and November 1984, and the diagnosis of human immunodeficiency virus--related disease was established from 26 to 54 months after operation. The survival time from diagnosis ranged from 8 days to 14 months in the 10 patients who have died. A clinical iDness developed in three of the patients immediately postoperatively that was consistent with primary human imniunodeficiency vims mononucleosis. The clinical features included a widevariety of opportunistic infections, but an abnormally high percentage of the patients first showed symptomsof dementiaor neoplasticdisease. In many patients, the diagnosis was not suspected for a prolonged period of time. On the basis of the prolonged incubation period, the incidence of this disease is 6kely to increase for several more years.
Mark Schiff, MD, Allan Katz, MD, Bruce Farber, MD, and Mark Kaplan, MD, Manhasset and New York, N.Y.
Acquired immunodeficiency syndrome (AIDS), described in 1981, has become an increasing public health problem in the United States and worldwide. As of this writing, 52,000 cases have been reported in this country, and the 3-year mortality rate exceeds 90%. Approximately 2% of the cases in the United States have resulted from transfusion of blood or blood products.' Since 1983, we have observed 25 cases of transfusion-related human immunodeficiency virus (HIV) infection in a cohort of 435 patients with antibody to HIV. Within this group, 13 patients acquired the disease after cardiothoracic operation. The relatively high incidence of AIDS after cardiothoracic operation seems worthy of investigation to determine whether any unusual features are present in this group. The clinical features of this illness are presented to enable physicians caring for these patients to recognize this devastating complication of cardiothoracic operation.
Methods We have attempted to detect HIV infection in hospitalized patients by serologic assay since June 1984. Initial assays were
From the Departmentof Medicine, Divisions of Pulmonary Medicine and Infectious Disease & Immunology, North Shore University Hospital, Manhasset, N.Y., and the Department of Medicine, Cornell University Medical College, New York, N.Y. Received for publication Dec. 4, 1987. Accepted for publication July 12, 1988. Address for reprints: Mark Schiff, MD, Division of Pulmonary Medicine, North Shore University Hospital, 300 Community Dr., Manhasset, NY 11030.
126
done in the Laboratory of Tumor and Cell Biology of the National Cancer Institute in conjunction with Dr. M. G. Sarngadharan and Dr. Robert C. Gallo and were later done in our own laboratory. Patients entered in this study had serologic tests performed after informed consent was obtained. Serum was stored at -20 C. This study was approved by our investigational review board. Antibody to HIV was detected with the use of standard enzyme-linked immunosorbent assays and confirmed by Western blot tests with human T-cell Iymphotrophic virus III antigen prepared by growing an HIV isolate in the H 9 cell line. Antigen was purified by sucrose density gradient centrifugation and disrupted by lysing antigen with radioimmunoprecipitation antigen buffer as previously described.' Western blot tests were done on 3 mm strips of antigen separated first in 12% Laemelli gels and then transferred to nitrocellulose eiectrophoretically. Antibody was detected after strips were soaked in serum at a dilution of 1:50. Antibody bands were visualized with the use of horseradish peroxidase conjugated goat anti-human antibody and appropriate substrate. Identification of the P21 and P41 bands was required tor diagnosis of HIV. T-cell subset tests were performed by methods previously described.' We 4 have been systematically screening patients at high risk for HIV infection since the discovery of HIV in samples contributed from our patients. All patients with clinical features of HIV infection, class IV, as defined by the Centers for Disease Control,' were tested after informed consent was obtained. Screening has been targeted particularly toward patients in the identified high-risk groups including those with a history of blood transfusion. The subjects of this report had no known risk factors other than transfusion in association with cardiac operation. 0
Results Thirteen patients had HIV infection with one or more features of AIDS after undergoing cardiothoracic oper-
Volume 97 Number 1
Development of AIDS after cardiothoracic surgery
January 1989
127
Table I Patient
Age* (yr)
Sex
I
2
54 62
M M
3 4
62 73
M
5 6 7 8 9 10
55 58 60 7
M M M
II
12 13
60
23 66 47 57
F
F F M
F M M
Date of operation
1/81 7/81 3/83 [repeat] 9/81 3/82 6/82 [repeat] 5/82 6/82 8/82 4/81 11/84 11/81 3/83 10/82 3/83
Type of operation
Date of HIV Dxt
Date of death
CABG CABG
6/83 4/84
7/84 3/85
CABG CABG
7/84 6/85
11/84 11/85
Aortic valve replacement CABG CABG Tetralogy of Fallot repair Aortic valve replacement Tetralogy of Fallot repair CABG CABG CABG
3/86 9/86 4/86 10/85 1/87 6/86 2/86 10/87 1/87
5/86 9/86 6/87 Alive Alive 10/86 2/86 Alive Alive
CABG, Coronary artery bypass grafting; Dx, diagnosis. •Age of patient at time of AIDS diagnosis. tDate at which the patient first required treatment for an opportunistic infection that confirmed the diagnosis of AIDS.
ation; 10 of these have died. The age range at the time of diagnosis was 7 to 73 years. The operations were performed between January 1981 and November 1984, all but three in 1981 and 1982. The patients exhibited manifestations of HIV infection leading to diagnosis from June 1983 to October 1987. The operations performed included coronary artery bypass grafting (11 operations in nine patients), aortic valve replacement (twopatients), and correction of tetralogy of Fallot (two patients). The diagnosis of AIDS or AIDS-related complex was established between 26 and 54 months after operation, and survival from time of diagnosis ranged from 8 days to 14 months in the 10 patients who havedied (see Table I). The clinical features of AIDS in our patients included a variety of infections. Seven patients had a single episode of Pneumocystis carinii pneumonia. Four patients had disseminated Mycobacterium avium-intracellulare isolated from blood and stool, Candida esophagitis was found in four cases, and Cryptosporidium was isolated from stool in two patients.A number of bacterial and viral infections were also seen and are detailed in Table II. A variety of neoplastic conditions occurred in our patients as well. Two patients had colon cancer, one had thyroid cancer with metastatic disease, three had lymphomas, and one had Kaposi's sarcoma. One had multiplebasal cell carcinoma of the skin. Three of these tumors occurred in a single patient (colon carcinoma, Kaposi's sarcoma, diffuse histocytic lymphoma). Five of 13 patients initially showed symptoms of progressive dementia, and dementia or other disturbances of psychomotor function developed in five more patients (see Table 11). Early signs included memory
loss, confusion, and lethargy. These findings often preceded a definite diagnosis of AIDS. The encephalopathy was rapidly progressive over 3 to 6 months. Six patients became immobile, incontinent, and essentially nonverbal by the time of final hospitalization. One patient had received psychiatric treatment for depression before the diagnosis became apparent. Several miscellaneous features of disease in our patients deserve comment. The operations were performed in 10 different hospitals, but all patients received blood from The Greater New York Blood Program. We do not have information regarding the proportion of transfusions in these institutions used to support the cardiac surgery programs. Three patients had a febrile illness documented in the postoperative period, each with atypical lymphocytes noted on peripheral smear. Serum from three spouses (of seven tested) was positive for HIV. AIDS has not developed in these three spouses, but two have lymphadenopathy and two appear to have early signs of dementia. In one of these cases, female-to-male transmission of the virus occurred. None of the spouses tested had any other known risk factor for HIV infection.
Discussion Among the cases of transfusion-related HIV infection seen in our institution, those involving cardiothoracic operations account for 40%. The relatively large number of cases we have seen relates to our proximity to New York, a metropolitan area with early and subsequently heavy prevalence of HIV -infected persons. It was therefore inevitable that this infection would affect the blood donor pool in our region. A unit of HIV-infected blood
The Journal 01 Thoracic and Cardiovascular
1 2 8 Schiff et al.
Surgery
Table II Patient
T-cell subset ratio (T4-T8) 0.3
2
0.07
3
0.4 0.1
4
0.26
5 6 7
0.26
8 9 10
0.9 0.5 0.05
ND
11
ND
12 13
0.04 0.3
Infections
Neoplasias
Candida esophagitis, herpetic stomatitis, PCP,
disseminated MAl PCP, Klebsiella, Pseudomonas, Staphylococcus aureus pneumonia, HSV, MAl, Cryptosporidium (stool) Candida esophagitis HSV, MAl, PCP Pseudomonas pneumonia, Escherichia coli sepsis, Campylobacter (stool) Candida esophagitis, Cryptosporidium, PCP PCP, herpes zoster Disseminated Mycobacterium tuberculosis Candida
Lymphadenopathy PCP PCP Chronic sinusitis Chronic diarrhea, weight loss
Dementia
Kaposi's sarcoma, DHL, colon None
Severe depression
Colon None
Severe depression dementia Severe dementia
DHL None Multiple basal cell cancers None Thyroid carcinoma Large cell lymphoma None None None
Dementia Severe dementia Severe dementia
Parkinson's disease
Psychomotor retardation None Retarded from birth Unknown Depression None
PCP, Pneumocystis carinii pneumonia; DHL, diffuse histiocytic lymphoma; HSV, herpes simplex virus; MAl, Mycobacterium avium-imracellulare; ND, not done.
has a high likelihood of transmitting infection to the recipient. Current data suggest at least 90% of persons who received such blood have become HIV antibody positive.v" Most of our cases were diagnosed after a clinical illness arose. The median latency from time of operation to diagnosiswas nearly 3 years. Most of our patients had been ill from 3 to 6 months preceding diagnosis. The disease tended to be rapidly progressive in these patients, with survival less than 1 year in all but one case. The clinicalfeatures seen in our patients have all been described in AIDS but the prevalence of central nervous system involvement and neoplasm was uniquely high,"" The opportunistic infections were similar to those described in the AIDS populationat large and included Pneumocystis carinii pneumonia, Mycobacterium infections, and Candida in many cases. There were several episodes of bacterial sepsis, pneumonia, and diarrhea consistent with depressed immunity in these patients. The T4:T8 ratio averaged 0.3 at the time of diagnosis, which indicated severe depression in helper T-cell numbers. Of note was a clinical illness in three patients immediately postoperatively consistent with HIV viremia as previously described by Ho and associates." This illness, consisting of a mononucleosis-like syndromewith fever, malaise, and lymphocytosis, may be confusing in the patient having a cardiac operation. It can be mistaken for postperfusion syndrome or postpericardiotomy syndrome. The incidence of severe progressive
dementia in many of our patients was noteworthy. This syndromeis thought to be due to direct HIV infection of brain tissue. Clinical features are those of a rapidly progressive dementia beginningwith apathy, depression, and memory lossand developing into full-blown dementia.' Although 60% to 90% of patients with AIDS have some neurologic manifestations, the presence of AIDS dementia in virtually all of our patients represents a higher percentage than that usually reported.' The presence of severe dementia at the onset of illness has been uncommon among our remaining AIDS population. We can only speculate as to the reasons for this. Postmortem studies show that neuropathic changes are present in 90% of patients dying of AIDS. 10 Because an older age group is at risk for AIDS after cardiothoracic operation, the neurologic involvement may become clinically evident earlier. Recognition of this syndrome, the earliest presenting sign in many of our patients, is important. Symptoms may otherwise be attributed to depression or Alzheimer's disease. Evaluation of these patients for other AIDS-related manifestations that may affect the central nervous system is important. None of our patients had serologic evidence of syphilis or toxoplasmosis or evidence of central nervous systemlymphoma on computed tomographic scan. We also observed a high incidence of neoplastic disease in these patients: two had coloncancer, one had thyroid cancer, one had multiple basal carcinoma, three had lymphoma, and one had Kaposi's sarcoma. Well
Volume 97 Number 1 January 1989
have previouslyreported a high incidence of solid tumors and lymphomas in patients with HIV infection in our institution. The incidence of lymphoma in patients with AIDS is known to be increased. The incidence of solid tumors in these patients may simply reflect the chance concurrence of these two diseases. Alternatively, it may be a consequence of disordered immune function. Presumably, the progressive loss of the immune function including the surveillance function allows the expression of latent tumors. The high prevalence of solid tumors and lymphomas in this small group of patients may reflect the increase in endemicity of cancer in this age group, which becomes manifest after collapse of the immune system. The advent of HIV antibody screening of banked blood will greatly reduce the threat of HIV infection in patients undergoing cardiothoracic operations in the future.' However, latency of this disease was 3 years in our patients. This implies that a large group of patients are still at risk. The number of AIDS cases has increased greatly since 1981; and the number of symptom-free infected persons is thought to be much larger. Thus the incidence of infection in the donor pool may well have been increasing up to the advent of large-scale screening in May 1985. The risk of contracting AIDS after operation might therefore be expected to peak in 1988. Alternatively, this may represent an early peak with additional cases developing with time. A recent estimate of the latency of HIV infections after transfusion is 54 months." Awareness of this problem, and early detection of cases, would be helpful in limiting further spread of the disease. We know, for example, that three spouses of seven tested among our patients have acquired the infection. This is a high proportion, in light of the significance of this disease. In addition, affected patients, once identified, might be offered azothymidine" in hopes of reducing morbidity and extending their lives. REFERENCES 1. Centers for Disease Control. Human immunodeficiency virus infection in transfusion recipients and their family members. MMWR 1987;36:137-40.
Development of AIDS after cardiothoracic surgery
129
2. Sarngadharan MG, Popovic M, Bruch L, Schurpbach J, Gallo RC. Antibodies reactive with human T-1ymphotrophic retroviruses in the serum of patients with AIDS. Science 1984;224:506-8. 3. Pahwa S, Kaplan MH, Fikrig S, et al. Spectrum of human T-cell lymphotrophic virus type III infection in children. JAMA 1986;255:2299-305. 4. Gallo RC, Salahuddin SZ, Popovic M, et al. Frequent detection and isolation of cytopathic retroviruses (HTLV 1Il) from patients with AIDS and at risk for AIDS. Science 1984;224:500-3. 5. Centers for Disease Control. Classification system for human T-lymphotrophic virus type IIljlymphadenopathy-associated virus infection. MMWR 1986;35:334-9. 6. Hove JR. Transfusion-associated hepatitis and AIDS: what is the risk. N Engl J Med 1987;317:242-5. 7. Snider WO, Simpson DM, Nielson S, Gold JWM, Metreka CE, Posner JB. Neurologic complications of acquired immunodeficiency syndrome: analysis of 50 patients. Ann Neurol 1983;14:403-18. 8. Ho DD, Pomeranz RJ, Kaplan Jc. Pathogenesis of infection with human immunodeficiency virus. N Engl J Med 1987;317:278-86. 9. Ho DD, Samgadharan MG, Resnick L, et al. Primary human T-lymphotrophic virus type III infection. Ann Intern Med 1985;103:880-3. 10. Neilson SL, Petito CK, Winachor CD, Posner JB. Subacute encephalitis in acquired immunodeficiency syndrome: a post-mortem study. Am J Clin Pathol 1984; 82:678-82. 11. Kaplan MH, Susin M, Pahwa SG, et al. Neoplastic complications of HTLV-1Il infection. Am J Med 1987;82:389-95. 12. Lui KJ, Lawrence ON, Morgan WM, et al. A mode1based approach for estimating the mean incubation period of transfusion associated acquired immunodeficiency syndrome. Proc Nat! Acad Sci USA 1986;83:3051-5. 13. Fishel MA, Richman DD, Grieco MH, et al. The efficacy of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS related complex. N Engl J Med 1987:317:185-91.