The impact of surveillance and rapid reduction in immunosuppression to control BK virus‐related graft injury in kidney transplantation

We prospectively screened 609 consecutive kidney (538) and kidney‐pancreas (71) transplant recipients for BK viremia over a 4‐year interval using polymerase chain reaction viral load detection and protocol kidney biopsies. We found that BK viremia is common at our center: total cases 26.7%, cases during first year 21.3% (mean 4 months), and recipients with ≥10 000 copies/ml 12.3%. We found few predictive clinical or demographic risk factors for any BK viremia or viral loads ≥10,000 copies/ml, other than prior treatment of biopsy confirmed acute rejection and/or higher immunosuppressive blood levels of tacrolimus (P = 0.001) or mycophenolate mofetil (P = 0.007). Viral loads at diagnosis (<10 000 copies/ml) demonstrated little impact on graft function or survival. However, rising copy numbers demand early reductions in immunosuppressive drug doses of at least 30–50%. Viral loads >185 000 copies/ml at diagnosis were predictive of BK virus‐associated nephropathy (BKVAN; OR: 113.25, 95% CI: 17.22–744.6, P < 0.001). Surveillance for BK viremia and rapid reduction of immunosuppression limited the incidence of BKVAN to 1.3%. The addition of leflunomide or ciprofloxacin to immunosuppressive dose reduction did not result in greater rates of viral clearance. These data support the role of early surveillance for BK viremia to limit the impact on transplant outcome, although the most effective schedule for screening awaits further investigation.     

Effect of the TNF-alpha-promoter polymorphism on cardiac allograft rejection.

BACKGROUND: A polymorphism exists in the tumor necrosis factor alpha (TNF-alpha) promoter (position -308, G/A = TNFA1/TNFA2). The TNFA2 allele is associated with increased TNF-alpha production in vitro and has been reported to increase the risk of allograft rejection in pediatric recipients of cardiac transplantation. We examined the effect of the TNFA2 allele on the risk of allograft rejection in adult cardiac transplant recipients. METHODS: We prospectively analyzed 57 subjects (aged 54 +/- 11 years, 84% men, 49% ischemic) who underwent cardiac transplantation between October 1996 and July 2001. Patients were observed after transplantation (mean, 910 +/- 605 days) and the frequency of allograft rejection (biopsy Grade > or =2) in patients with the TNFA2 allele (Group A, n = 15) was compared with TNFA1 homozygotes (Group B, n = 42). Overall survival and time to rejection episodes also were compared between groups. RESULTS: The frequency of allograft rejection was similar between groups (Group A, 8/15 [56%]; Group B, 22/42 [52%]; p = 0.77). Time to rejection also was comparable (Group A, 17 +/- 11 days; Group B, 20 +/- 20 days, p = 0.74). Overall post-transplant survival was similar between groups (1- and 2-year percentage survival: Group A, 87% and 78%, Group B, 88% and 82%, p = 0.35). CONCLUSION: The TNFA2 allele was not associated with increased risk of rejection in adult cardiac transplant recipients. The impact of this polymorphism on overall post-transplant outcomes will require investigation in larger multicenter studies.     

Evaluation of fluorodeoxyglucose positron emission tomography imaging in metastatic transitional cell carcinoma with and without prior chemotherapy

INTRODUCTION: This study was designed to determine the value of fluorodeoxyglucose (FDG) positron emission tomography (PET) in the evaluation of metastatic transitional cell carcinoma (TCC). METHODS: Fifty-eight FDG PET scans were performed on 46 consecutive patients with TCC. Results were correlated with radiologic, pathologic, and histologic findings in these patients and the sensitivity of PET for detecting malignancy in untreated TCC patients (n = 48) was compared to the sensitivity in patients who had undergone prior chemotherapy (n = 10). RESULTS: Of 48 scans in patients who had no prior systemic chemotherapy, 10 had increased uptake in proven metastatic TCC lesions and 3 PET studies failed to reveal metastatic TCC (sensitivity 76.9%). In patients free of metastatic disease, 33 revealed no abnormal uptake and 1 study revealed a suspicious area in a patient free of metastases (specificity = 97.1%). However, in 10 patients imaged after receiving chemotherapy, the sensitivity fell to 50% for the detection of histologically confirmed residual/recurrent tumor by PET. CONCLUSIONS: FDG PET detects increased metabolic activity. After chemotherapy, viable cancer cells may still be present but with a diminished metabolic rate. As a result, PET imaging is often useful in the evaluation of untreated metastatic TCC metastasis but should be interpreted with caution in patients who have received prior chemotherapy.     

Repeatability of hypoxia PET imaging using [<Superscript>18</Superscript>F]HX4 in lung and head and neck cancer patients: a prospective multicenter trial

Purpose

Hypoxia is an important factor influencing tumor progression and treatment efficacy. The aim of this study was to investigate the repeatability of hypoxia PET imaging with [¹⁸F]HX4 in patients with head and neck and lung cancer.

Methods

Nine patients with lung cancer and ten with head and neck cancer were included in the analysis (NCT01075399). Two sequential pretreatment [¹⁸F]HX4 PET/CT scans were acquired within 1 week. The maximal and mean standardized uptake values (SUV_max and SUV_mean) were defined and the tumor-to-background ratios (TBR) were calculated. In addition, hypoxic volumes were determined as the volume of the tumor with a TBR >1.2 (HV_1.2). Bland Altman analysis of the uptake parameters was performed and coefficients of repeatability were calculated. To evaluate the spatial repeatability of the uptake, the PET/CT images were registered and a voxel-wise comparison of the uptake was performed, providing a correlation coefficient.

Results

All parameters of [¹⁸F]HX4 uptake were significantly correlated between scans: SUV_max (r?=?0.958, p?<?0.001), SUV_mean (r?=?0.946, p?<?0.001), TBR_max (r?=?0.962, p?<?0.001) and HV_1.2 (r?=?0.995, p?<?0.001). The relative coefficients of repeatability were 15 % (SUV_mean), 17 % (SUV_max) and 17 % (TBR_max). Voxel-wise analysis of the spatial uptake pattern within the tumors provided an average correlation of 0.65?±?0.14.

Conclusion

Repeated hypoxia PET scans with [¹⁸F]HX4 provide reproducible and spatially stable results in patients with head and neck cancer and patients with lung cancer. [¹⁸F]HX4 PET imaging can be used to assess the hypoxic status of tumors and has the potential to aid hypoxia-targeted treatments.

     

Decision making in primary sacral tumors

Background contextPrimary tumors of the sacrum are extremely rare lesions. Their management is governed by an interplay of complex factors. Appropriate decision making is crucial to obtain the best possible outcome in terms of maximizing disease control while attempting to minimize neurological dysfunction.PurposeOur study presents the results of a group of patients with primary tumors of the sacrum who were surgically treated by the same multidisciplinary team at a specialist oncology center over a relatively short period of time (5 years).Study design/settingPatients were identified by a retrospective review from a prospectively maintained database.Patient sampleBetween January 2000 and December 2005, 17 primary sacral tumors were surgically treated at our institution, a referral center for oncology.Outcome measuresWe evaluated the outcome in terms of local disease control, residual neurological dysfunction, and complications as a result of surgical intervention.MethodsThere were 12 males and 5 females. The diagnosis included chordoma in six patients, giant cell tumor in seven patients, aneurysmal bone cyst in two patients, and a chondrosarcoma and an osteoblastoma in one patient each. Sixteen of these patients were analyzed. Four lesions had their upper extent at S1, six lesions had their upper extent at S2, four lesions had their upper extent at S3, and two lesions were below S3. Ten cases were treated with wide excision and underwent partial sacral amputations. Five cases had a midline sacral amputation through S1, three through S2, and two through S3. Six benign lesions were treated with curettage. None of the patients received chemotherapy. Four cases received postoperative radiation. The follow-up duration ranged from 18 to 44 months with a mean of 31 months.ResultsNone of the six patients who presented with loss of bladder and bowel control regained it after surgery. Of the 10 patients who had intact bladder and bowel control preoperatively only 4 retained bladder and bowel control postoperatively. Of the six patients who lost bladder and bowel control postoperatively, four patients had a wide excision where bilateral S2 roots were sacrificed. The other two cases in whom the disease extended up to S1 had curettage. Local recurrence occurred in 4 of the 10 lesions treated with wide excision. All the patients who had inadequate margins recurred. Local recurrence occurred in two of the six lesions treated with curettage. Three of the four cases who received postoperative irradiation developed recurrence. Our wound complication rate was 13%.ConclusionWide resection with adequate margins gives the best chance of local control and should be the surgery of choice for all malignant primary sacral tumors and in benign lesions involving lower segments when preservation of both S3 roots is possible. Intralesional curettage has a higher risk of local recurrence without providing the certainty of retaining neurological function. To retain bladder and bowel control and minimize neurological dysfunction, it may be worthwhile managing benign sacral tumors that extend above S3 with serial embolization. The administration of parentral bisphosphonates may prove beneficial in cases of giant cell tumor managed with serial embolization.     

Unusual intraosseous transmigration of impacted tooth

Transmigration of an impacted tooth through the symphyseal suture is a rare and special developmental anomaly of unknown etiology that is unique to the mandibular canine. Maxillary canine transmigration is even rarer. Transmigrated canines are particularly significant due to the aesthetic and functional importance. A maxillary lateral incisor crossing the mid-palatal suture has never been reported in the literature. The aim of this report is to present the first case of simultaneous transmigration of a lateral incisor and canine in the maxilla. The paper also reports four unusual cases of unilateral canine transmigration in the maxilla and mandible and successful eruption of one of the transmigrated mandibular canines following orthodontic traction. Etiology of transmigration and its clinical considerations are also discussed.     

Inflammation and dry eye disease—where are we?

The presence of inflammation in dry eye disease (DED) results in increased patient symptomatology, ocular surface damage and worsening tear dysfunction. It also affects the health of meibomian glands and their secretions which further aggravates ocular surface disease. This article reviews current knowledge regarding ocular surface inflammation in DED and explores the relationships between the vicious cycles of DED, inflammation and meibomian gland dysfunction (MGD). The clinical evaluation of eyes with such changes, markers that identify the presence of inflammation on the ocular surface and current treatment options are discussed.     

Utilization of eye care services among those with unilateral visual impairment in rural South India: Andhra Pradesh Eye Disease Study (APEDS)

AIM: To report on the utilization of eye care services and its associated factors among those with unilateral visual impairment (VI) in a rural South Indian population. METHODS: A population based cross-sectional study was conducted in three districts (Adilabad, Mahbubnagar and West Godavari) in the state of Andhra Pradesh, India. A detailed interview and a comprehensive eye examination were conducted. Those with unilateral VI were asked questions about noticing any change in vision and on utilization of eye care services. The most important reason reported by the participant for not utilizing the services was used for the analysis. Multiple logistic regression models were used to examine the association between noticing a change in vision and socio-demographic variables such as age, gender, education and area of residence, severity and causes of VI. RESULTS: Among the 4456 participants aged ≥16y who were administered the questionnaire, 53.2% were women, and 54.7% had no education. Of the 489 (11%; 95% CI: 10.1-11.9) people with unilateral VI, 399 (81.6%) participants reported noticing a change in their vision over the last five years but only 136 (34.1%) participants had sought eye care consultation. Those who had any education (OR: 1.9; 95% CI: 1.1-3.2), had blindness (OR: 2.7; 95% CI: 1.4-5.2), and cataract (OR: 2.1; 95% CI: 1.0-4.3) as a cause of unilateral VI were more like to seek eye care consultations. The most commonly reported reasons for not seeking eye care services were “do not have money for eye checkup” in 30.7% of the participants followed by “do not have a serious problem” (30.0%). CONCLUSION: A large proportion of rural population though noticed a change in their vision did not seek eye care due to financial and person-related reasons. Eye care service providers need to address these barriers to enhance the uptake of eye care services among those with unilateral VI.     

Quantitative estimation and recommendations for supplementation of protein lost through scaling in exfoliative dermatitis

BACKGROUND: Exfoliative dermatitis (ED) can result in protein loss due to scaling causing a negative nitrogen balance. Freedberg and Baden (J Invest Dermatol 1962; 38: 277-284) estimated the amount of scale lost in ED by collecting it in an occlusive suit. Subsequently, the nitrogen content was determined by the Kjeldahl method. The exact amount of protein supplementation in ED, dependent on scale loss, is not well established. As occlusion and hyperthermia caused by the suit can inhibit scaling, the objectives of the present study were to design an alternative method to measure the amount of scale lost, to estimate the protein content of the scale, and to propose suitable recommendations for protein supplementation. METHODS: In 40 patients with ED, the total protein content lost through scaling per day (P) was determined by the following equation: P = TxIxYxX/25x10(4) g, where T is the total body surface area in square meters, I is the percentage area involved in scaling, estimated using computer-aided design (CAD graph), Y is the amount of scale lost per unit area (0.0025 m2) in milligrams, and X is the quantity of protein present in 1 g of scale in milligrams estimated by a spectrophotometer. RESULTS: It was observed that patients with ED secondary to drug reactions, eczema, and psoriasis lost 7.2, 9.6, and 22.6 g of scale with a protein content of 4.2, 5.6, and 12.8 g respectively. The difference in the amount of protein lost in ED secondary to drug reactions and eczema was not statistically significant; however, the protein lost in psoriasis was significant (p < 0.01 to p < 0.05). CONCLUSIONS: ED may increase the daily protein loss by approximately 25-30% in psoriasis and 10-15% in other causes. Standard treatment for ED and protein supplementation based on our recommendations can minimize the adverse effects of a negative nitrogen balance.