Monitoring systemic donor lymphocyte macrochimerism to aid the diagnosis of graft-versus-host disease after liver transplantation

BACKGROUND: The diagnosis of graft-versus-host disease (GvHD) after liver transplantation can be difficult because early symptoms are often nonspecific. In this study, the presence of donor lymphocyte macrochimerism in recipient peripheral blood was examined as a diagnostic aid for GvHD after cadaveric donor liver transplantation. METHODS: Between 1996 and 2002, 33 liver transplant recipients with a clinical suspicion of GvHD (skin rash, diarrhea, pyrexia, pancytopenia, or anemia, without an obvious alternative cause) were investigated for peripheral blood donor lymphocyte macrochimerism. Donor macrochimerism was determined at the time of first clinical presentation by a low-sensitivity polymerase chain reaction (PCR) to detect donor human leukocyte antigen (HLA) alleles using genomic DNA extracted from recipient peripheral blood. Where donor HLA alleles were detected, the percentage of donor T cells was quantified by two-color flow cytometric analysis using antibodies specific for mismatched donor and recipient HLA alleles. The relationship between the presence or absence of donor lymphocyte macrochimerism and final diagnoses based on clinical and histological criteria was examined. RESULTS: Seven of the 33 patients were PCR positive for donor HLA alleles. All had macrochimerism, with donor T lymphocyte levels ranging from 4% to 50% of circulating lymphocytes. All seven patients had normal liver function tests, skin rash, and diagnosis of GvHD histologically confirmed by skin or gut biopsies. Twenty-six patients were PCR negative, and, in 23, an alternative diagnosis was eventually established. The remaining three patients made a rapid and spontaneous recovery with no further symptoms suggestive of GvHD. CONCLUSIONS: Donor lymphocyte macrochimerism was present in all patients in whom the diagnosis of GvHD was confirmed. In patients with symptoms consistent with GvHD and a negative PCR for donor HLA, an alternative diagnosis was eventually established or the patients recovered spontaneously. Detection of donor HLA alleles in recipient peripheral blood by PCR is a useful diagnostic tool for GvHD after liver transplantation.     

Nonablative 1450-nm Diode Laser in the Treatment of Facial Atrophic Acne Scars in Type IV to V Asian Skin: A Prospective Clinical Study

BACKGROUND: There is presently little published data on the clinical effectiveness of nonablative lasers in the treatment of atrophic acne scars and the safety of their use in patients with darker skin types. OBJECTIVE: This study aims to determine the clinical effectiveness and safety of the nonablative 1450 nm diode laser with cryogen cooling spray in the treatment of facial atrophic acne scars in Type IV-V Asian skin. METHODS: This is a prospective non-comparative open study. 4 to 6 laser treatment sessions were performed on patients with atrophic acne scars. Final clinical assessment was performed 6 months after the last treatment. RESULTS: 57 patients were evaluated. Patient's self-assessment of scar improvement as compared with doctor's assessment was as follows: patients who completed 4 treatments (15.7% vs 6.6%), patients who completed 5 treatments (20% vs 7.9%) and patients those who completed 6 treatments (17.3% vs 5.0%). Main side effects were mild to moderate pain during the procedure, transient erythema, and hyperpigmentation which occurred in 39% of treated patients. CONCLUSION: The nonablative 1450 nm diode laser may be effective in achieving mild to moderate gradual clinical improvement in the treatment of facial atrophic acne scars. The procedure is associated with minimal downtime and is safe for use in darker skin types IV and V.     

Infected common iliac artery aneurysm repaired in an infant with cadaveric vein graft

Aneurysms are rare in children. Causes include congenital, traumatic, inflammatory, and infectious etiologies. When and how to best surgically treat arterial aneurysms in a child remain unclear. We present the case of a 3-month-old child with an aneurysm of the left common iliac artery, which was first detected on abdominal ultrasound and was successfully repaired with a cadaveric vein graft.     

Vascular Access in Hemodialysis Patients with Central Venous Obstruction or Stenosis: One Center’s Experience

The purpose of this study was to evaluate the value of complex hemodialysis access procedures among patients with central venous obstruction who were running out of access sites. Between September 2002 and December 2003 we performed a total of 640 new hemodialysis access procedures in 3 renal units. Ten of these patients presented central vein stenosis or obstruction and were not suitable for peritoneal dialysis. Each of the 10 patients had 3 or 4 previous failed access procedures and numerous infected central lines and their dialysis catheters were not functioning adequately. Nine patients presented with a severely stenosed or occluded superior vena cava and 1 had both subclavian veins occluded. Three patients were diabetics, 2 were obese and 6 had hypertension. We performed 12 procedures on these 10 patients. Saphenous veins were used 6 times, twice as a loop to the femoral artery and 4 times as a transposition to the popliteal artery above the knee. Femoral vein transposition to the popliteal artery was carried out in 2 cases. We performed 3 axillary artery to popliteal vein polytetrafluoroethylene (PTFE) bypasses, 1 on an obese woman who had no saphenous vein and was not suitable for a femoral vein transposition, 1 on a diabetic woman whose saphenous vein loop clotted after 5 months and 1 on a female patient with severe peripheral vascular disease. The patient with bilateral subclavian vein occlusion had a brachial artery to internal jugular vein PTFE graft. The PTFE graft to the jugular vein has been patent and regularly needled with a follow-up of 4 months. Four saphenous vein fistulae were regularly used for dialysis; 2 were never used. Five saphenous fistulae clotted after an average life span of 4 months (range 3 weeks-9 months) and 1 is still patent and in use (5 months). Both femoral vein transpositions have been patent and have been needled 3 times a week with a follow-up of 10 and 4 months; one had to be revised surgically after 9 months. Of the 3 axillary artery to popliteal vein grafts, 1 had to be tied off after a week because of severe steal syndrome and 2 have been patent (20 months follow-up) and have been needled regularly ever since. Seventy percent of these patients have been dialyzed line-free through their fistula despite severe central vein stenosis or obstruction for periods of 9-18 months when this review was undertaken. Although the follow-up needs to be longer, we discuss the surgical, radiologic, and dialysis features of these patients and propose a management pathway for central vein stenosis or occlusion.     

Transesophageal echocardiography-related gastrointestinal complications in cardiac surgical patients

OBJECTIVE: The aim of this audit was to determine the incidence of major gastrointestinal (GI) complications associated with intraoperative transesophageal echocardiography (TEE) in adult cardiac surgical patients in this institution. DESIGN: Retrospective database audit. SETTING: University-affiliated teaching hospital. PARTICIPANTS: Eight hundred fifty-nine consecutive cardiac surgical patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The records of all patients who developed a major upper GI complication within 30 days of cardiac surgery between January 2001 and May 2003 were examined. The patients were identified by cross-referencing cardiac surgery and endoscopy databases. A major GI complication was defined as a perforation of the esophagus or stomach or upper GI bleeding requiring transfusion, endoscopic, or surgical intervention. Early presentation was defined as <24 hours; late presentation was defined as >24 hours. During the audit period, 859 patients underwent cardiac surgery. Five hundred sixteen patients had cardiac surgery with TEE (group 1), and 343 patients had cardiac surgery without TEE (group 2). Six patients were identified, 1.2% (95% confidence interval [CI], CI, 0.5%-2.5%) in group 1 who had a major upper GI complication consistent with TEE injury. Two patients, 0.38% (95% CI, 0.05%-1.40%), presented early, and 4 patients, 0.76% (95% CI, 0.21%-1.98%), presented late. One patient in group 2 developed a major upper GI complication, 0.29% (95% CI, 0.01%-1.6%). CONCLUSION: The incidence of major GI complications attributed to TEE in this group of cardiac surgical patients was higher than previously reported. Late presentation was more common than early presentation. Previous studies that have not included late presentations may have underestimated the true incidence of major GI complications related to TEE.     

Alemtuzumab (CAMPATH 1H) Induction Therapy in Cadaveric Kidney Transplantation—Efficacy and Safety at Five Years

Alemtuzumab is a powerful lymphocyte depleting antibody currently being evaluated in solid organ transplantation. This paper describes 5-year results of a single center study of alemtuzumab as induction in renal transplantation. Thirty-three renal transplant recipients received 20 mg alemtuzumab on day 0 and 1, followed by half-dose cyclosporin monotherapy (trough concentration 75-125 ng/mL) from day 3. They were compared in a retrospective contemporaneous-controlled manner with 66 kidney transplant recipients transplanted in the same period and center who received conventional immunosuppression with cyclosporin, azathioprine and prednisolone. In the alemtuzumab group 12% of recipients died compared to 17% in the control group (p = 0.48); likewise graft loss was similar in both groups (21% vs. 26%, respectively, p = 0.58). Incidence of acute rejection was also comparable at 5 years (31.5% vs. 33.6%), although the pattern of rejection was different with 14% patients in the alemtuzumab group experiencing rejection over 1 year post-transplant compared to none in the control group. There was no significant difference between groups in terms of infection or serious adverse events. While acknowledging the limitations of a relatively small single-center study, results suggest that alemtuzumab induction allowed satisfactory long-term patient and graft survival equivalent to that seen with standard triple immunosuppression, while avoiding steroid therapy.     

Affluence and Breast Cancer

High income, high socioeconomic status, and affluence increase breast cancer incidence. Socioeconomic status in USA breast cancer studies has been assessed by block‐group socioeconomic measures. A block group is a portion of a census tract with boundaries that segregate, as far as possible, socioeconomic groups. In this study, we used US Census income data instead of block groups to gauge socioeconomic status of breast cancer patients in relationship with incidence, prognostic markers, and survival. US state breast cancer incidence and mortality data are from the U.S. Cancer Statistics Working Group, United States Cancer Statistics: 1999–2011. Three‐Year‐Average Median Household Income by State, 2010 to 2012, is from the U.S. Census Bureau, Current Population Survey, 2011 to 2013 Annual Social and Economic Supplements. County incomes are from the 2005–2009 American Community Survey of the U.S. Census Bureau. The American Community Survey is an ongoing statistical survey that samples a small percentage of the population yearly. Its purpose is to provide communities the information they need to plan investments and services. Breast cancer county incidence and survival data are from the National Cancer Institute's Surveillance, Epidemiology and End Results Program (SEER) data base. We analyzed SEER data from 198 counties in California, Connecticut, Georgia, Hawaii, Iowa, New Mexico, Utah, and Washington. SEER uses the Collaborative Stage (CS) Data Collection System. We have retained the SEER CS variables. There was a significant relationship of income with breast cancer incidence in 50 USA states and the District of Columbia in White women (r = 0.623, p < 0.001). There was a significant relationship between node involvement and income in Whites in 198 USA counties. Income was significantly correlated with 5‐year relative survival in Whites with localized breast cancer. Income was not correlated with 5‐year survival of Black race (p = 0.364) or other races (p = 0.624). The multivariate general linear model with income as covariate, 5‐year survival by race as a dependent variable, showed a significant effect of income and White race on 5‐year survival (p < 0.001), unrelated to Black race (p = 0.780) or other races (p = 0.618). In men, we found a nonsignificant positive correlation between county breast cancer incidence and income (r = 0.098, p = 0.168). Breast cancer risk factors, such as delayed childbirth, less breast‐feeding, and use of hormone supplements, are more common in affluent women. Affluent women are more likely to have mammograms, which detect many cancers that might not otherwise be diagnosed. In addition, women in certain affluent ethnic groups—Ashkenazi Jews, Icelanders and the Dutch—are more likely to carry genetic mutations known to predispose to breast cancer. We hypothesize that women with more income can afford better cancer care and survive longer than poorer women. But our hypothesis does not explain why this effect should be limited to White women; or why node involvement increased with income in White women but not in Blacks or Hispanics. Further studies may be worthwhile.     

Central nervous system abnormalities in Fanconi anaemia: patterns and frequency on magnetic resonance imaging

Objective:

Fanconi anaemia (FA) is an inherited disease associated with congenital and developmental abnormalities resulting from the disruption of a multigenic DNA damage response pathway. This study aimed to define the MRI appearances of the brain in patients with FA in correlation with their genetic and clinical features.

Methods:

A review of the brain MRI in 20 patients with FA was performed. Pituitary size and frequencies of the radiological findings of individuals with FA and age-matched controls were determined.

Results:

Abnormalities were identified in 18 (90%) patients with FA, the commonest being a small pituitary (68%, p < 0.01 females and p < 0.001 males). In five cases (25%, p = 0.02), the pituitary morphology was also abnormal. Posterior fossa abnormalities were seen in six cases (30%, p = 0.01) including Chiari I malformation (n = 3), Dandy–Walker variant (n = 2) and cerebellar atrophy (n = 2). Six patients (30%, p = 0.01) had morphological structural variation of the corpus callosum (CC).

Conclusion:

The incidence of central nervous system (CNS) abnormalities in FA is higher than previously reported, with a midline predominance that points to impact in the early stages of CNS development. MRI brain imaging is important for endocrine assessment and pre-transplant evaluation and can make an important contribution to clinical decision-making.

Advances in knowledge:

The incidence of brain structural abnormalities in FA is higher than previously reported, with abnormalities of the posterior fossa, CC and pituitary being common. There is an association with gender and reduction in pituitary size which does not strongly correlate with biochemically evident endocrine abnormality.