Evaluation of tibial rotational alignment in total knee arthroplasty: a cadaver study

Various techniques exist for establishing tibial rotational alignment during total knee arthroplasty (TKA). The purpose of this study is to establish the most precise and reproducible method to assess tibial component rotational alignment during TKA by comparing the flexion-extension technique (ROM) and the Posterior-lateral Corner Locked Technique (PLCL). Twenty posterior stabilized TKAs were performed on cadavers. The rotation angles of the tibial components obtained using the two techniques were evaluated. The tibial component rotation axis obtained using the ROM technique and the PLCL method averaged, respectively, 0.35° (±4.2°) externally rotated and 0.34° (±3°) internally rotated to the Akagi line. No significant differences between the two methods were found and a high correlation exists between the two techniques (Pearson’s coefficient = 0.88). The ROM and PLCL techniques are both precise and reproducible methods to assess tibial component rotation during TKA. However, while the ROM technique is dependent on the correct positioning of the femoral component and the soft tissue balancing, the PCLC method is easier if a complete visualization of the posterior-lateral corner of the cut tibial plateau is achieved.     

High-resolution computed tomography in the diagnosis and follow-up of idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is the most common interstitial lung disease and is associated with a fatal prognosis. Familiarity with the typical appearances of IPF on high-resolution computed tomography (HRCT) is important, as in the appropriate clinical setting, it is often sufficient for establishing a confident diagnosis of IPF without the need for surgical biopsy. Moreover, HRCT can provide important prognostic information in IPF. This is noteworthy, as the course of IPF is variable, and many patients develop complications leading to respiratory failure and death. The purpose of this paper is to review the progress made towards a better understanding of the HRCT patterns of IPF.     

Investigation of 99mTc-labelling of recombinant human interleukin-2 via hydrazinonicotinamide

IntroductionInterleukin-2 (IL-2) when radiolabelled with ^99mTc has been proved useful in imaging the side of lymphocytic infiltration in patients with autoimmune disorders and plays a significant role as a T-cell imaging agent. However, the labelling procedures used so far appeared to be rather complex and laborious. The aim of present study was to develop an efficient procedure of ^99mTc-labelling of recombinant human interleukin-2 (rhIL-2) via hydrazinonicotinamide (HYNIC) to develop a dry kit formulation.MethodsVarious molar ratios of rhIL-2/HYNIC (from 1:2 to 1:12) were used at the conjugation step. The conjugates were purified on a PD-10 column to remove the excess of unbound HYNIC, as well as of any aggregates. The final peptide concentration was quantified by the BCA method, and the number of HYNIC molecules incorporated into a rhIL-2 molecule was determined based on the reaction with 2-sulfobenzaldehyde. The ^99mTc-labelling was optimized using various amounts of HYNIC–rhIL-2, ^99mTc, SnCl₂, tricine and nicotinic acid (NA). Quality control included GF-HPLC, ITLC, SDS-PAGE and biological assay. Biodistribution studies were performed in Swiss mice and Wistar rats.ResultsGenerally, the highest radiolabelling yields were achieved when the HYNIC–rhIL-2 conjugates of ca. 2–4 HYNIC molecule substitution ratios were used. The optimal pH of the reaction medium was found to be in the range of 6.5 to 7.0. GF-HPLC analysis indicated that monomer and aggregates of ^99mTc-HYNIC–rhIL-2 are formed during radiolabelling. At optimized conditions of wet radiolabelling, the ^99mTc-HYNIC–rhIL-2 monomer was obtained with radiochemical purity >99%, specific activity of ca. 4 GBq/mg rhIL-2 and overall yield of ca. 65%. The two-vial freeze-dried kit was prepared: the first vial contained 30 μg HYNIC–rhIL-2, co-ligands, buffer and antioxidant; the second vial contained tricine and SnCl₂. The monomer of ^99mTc-HYNIC–rhIL-2 was obtained by gel chromatography on a PD-10 column. No differences between labelled and unlabelled IL2 in terms of biological activity were observed.ConclusionsOur study shows that rhIL-2 can be efficiently radiolabelled with ^99mTc via HYNIC, with tricine and NA as co-ligands using a two-vial freeze-dried kit. This enables the preparation of sterile and ready-to-use ^99mTc-HYNIC(tricine,NA)-rhIL-2 within 1 h.     

Use of bivalirudin for heparin-induced thrombocytopaenia after thrombolysis in massive pulmonary embolism: a case report

A 68-year-old man was referred to the emergency department 6 h after onset of sudden acute dyspnoea. Immediate ECG showed sinus tachycardia with the typical S1-Q3-T3 pattern and incomplete right bundle branch block. The echocardiogram showed the presence of mobile thrombus in the right atrium, a distended right ventricle with free wall hypokinesia and displacement of the interventricular septum towards the left ventricle. Lung spiral computed tomography (CT) showed bilateral pulmonary involvement and confirmed the picture of a thrombotic system in the right atrium and caval vein. Thrombolytic treatment with recombinant tissue plasminogen activator (rt-PA) and heparin (alteplase 10 mg bolus, then 90 mg over 2 h) was administered. Six hours after thrombolysis bleeding gums and significant reduction in platelet count (around 50,000) were observed. Heparin was discontinued and bivalirudin (0.1 mg/kg bolus and 1.75 mg/kg per h infusion) plus warfarin was initiated and continued for 5 days until the international normalised ratio (INR) was within the therapeutic range (2.0–3.0) for 2 consecutive days, with concomitant platelet count normalisation. Lung spiral and lower abdominal CT before discharge did not show the presence of clots in the pulmonary arteries of the right and left lung. This case suggests that bivalirudin could offer promise for use in patients with heparin-induced thrombocytopaenia (HIT) after thrombolysis for massive pulmonary embolism.     

A lower-dose, lower-toxicity cisplatin–etoposide regimen for childhood progressive low-grade glioma

To characterize a population of pediatric high-grade astrocytoma (HGA) patients by confirming the proportion with a correct diagnosis, and determine prognostic factors for survival in a subset diagnosed with uniform pathologic criteria. Sixty-three children diagnosed with HGA were treated at the Johns Hopkins Hospital between 1977 and 2004. A single neuropathologist (P.C.B.) reviewed all available histologic samples (n = 48). Log-rank analysis was used to compare survival by patient, tumor, and treatment factors. Median follow-up was 16 months for all patients and 155 months (minimum 54 months) for surviving patients. Median survival for all patients (n = 63) was 14 months with 10 long-term survivors (survival >48 months). At initial diagnosis, 27 patients were grade III (43%) and 36 grade IV (57%). Forty-eight patients had pathology slides available for review, including seven of ten long-term surviving patients. Four patients had non-HGA pathology, all of whom were long term survivors. The remaining 44 patients with confirmed HGG had a median survival of 14 months and prognostic analysis was confined to these patients. On multivariate analysis, five factors were associated with inferior survival: performance status (Lansky) <80% (13 vs. 15 months), bilaterality (13 vs. 19 months), parietal lobe location (13 vs. 16 months), resection less than gross total (13 vs. 22 months), and radiotherapy dose <50 Gy (9 vs. 16 months). Among patients with more than one of the five adverse factors (n = 27), median survival and proportion of long-term survivors were 12.9 months and 0%, compared with 41.4 months and 18% for patients with 0–1 adverse factors (n = 17). In an historical cohort of children with HGA, the potential for long term survival was confined to the subset with less than two of the following adverse prognostic factors: low performance status, bilaterality, parietal lobe site, less than gross total resection, and radiotherapy dose <50 Gy. Pathologic misdiagnosis should be suspected in patients who are long term survivors of a pediatric high grade astrocytoma.     

Radiotherapy and concomitant temozolomide during the first and last weeks in high grade gliomas: long-term analysis of a phase II study

We tested the efficacy and safety of temozolomide (TMZ) when given concomitantly to radiotherapy only in the first and last weeks of treatment to patients affected by high grade gliomas. Conformal radiotherapy (CTV1: tumor bed + residual tumor if present + 1.5 cm, 5,940 cGy, 180 cGy/day; CTV2: oedema, 3,960 cGy, 180 cGy/day) was associated with TMZ, 75 mg/m² × 5 days, the first and last weeks of radiotherapy. Adjuvant chemotherapy with TMZ (150 mg/mq daily × 5 days, q28 on the first cycle, 200 mg/mq daily × 5 days, q28 for the following cycles) was given, after chemoradiation, until disease progression or up to 6 cycles. From October 2000 to December 2003, 29 patients (25 GBL, 86.2%; 4 AA, 13.8%) were enrolled in this study. Twenty-two patients (75.8%) received a median 6 cycles of adjuvant chemotherapy with TMZ (range 1–20). Hematological toxicity was absent during concomitant chemoradiation and mild in adjuvant therapy, while neurological toxicity (seizures) was observed only in one case. At a median follow-up of 66 months (range 3–96), median progression-free survival (PFS) was 8 months, with a 1- and 2-year PFS of 46.7 and 28.7%, respectively; median overall survival (OS) time was 21 months, with a 1- and 2-year OS of 69.2 and 42.3%, respectively. In our experience, TMZ proved to be effective even when given only during the first and the last week of radiotherapy, with lower hematological toxicity.     

Underuse of Anthracyclines in Women with HER‐2+ Advanced Breast Cancer

Anthracyclines are among the most active drugs in breast cancer. Because of excessive cardiotoxicity, their use in combination with trastuzumab has been discouraged in patients with human epidermal growth factor receptor (HER)‐2⁺ metastatic breast cancer. We sought to describe how this treatment paradigm influenced the use of anthracyclines in this patient setting. We analyzed a multi‐institutional database containing the treatment history of 450 patients who received at least one trastuzumab‐based regimen for HER‐2⁺ metastatic breast cancer. Patients were considered eligible for anthracyclines for metastatic disease if they were never exposed (NE) or had been previously exposed (PE) to an anthracycline in the neoadjuvant or adjuvant setting and had relapsed after 12 months from the last dose. We then assessed the use of anthracycline‐based therapy after failure with the first trastuzumab‐based regimen in eligible patients. Three‐hundred twenty‐one patients were considered eligible for anthracyclines. In total, 190 eligible patients developing disease progression during the initial trastuzumab‐based therapy were analyzed. An anthracycline was administered as first salvage treatment in 14 NE and two PE patients. Another 15 NE and nine PE patients received an anthracycline as a further line of therapy. Of 119 eligible patients who died from breast cancer, only 30 received an anthracycline for metastatic disease. In conclusion, despite the fact that two thirds of the patients receiving trastuzumab‐based therapy for HER‐2 metastatic breast cancer are eligible for anthracyclines, these drugs are infrequently used nowadays to treat trastuzumab‐refractory disease. A role for these compounds should be redefined in this patient subset.     

Diagnostic accuracy of 64-slice computed tomography coronary angiography for the detection of in-stent restenosis: A meta-analysis

Background

We sought to evaluate the diagnostic accuracy of 64-slice multi-detector row computed tomography (MDCT) compared with invasive coronary angiography for in-stent restenosis (ISR) detection.

Methods

MEDLINE, Cochrane library, and BioMed Central database searches were performed until April 2009 for original articles. Inclusion criteria were (1) 64-MDCT was used as a diagnostic test for ISR, with >50% diameter stenosis selected as the cut-off criterion for significant ISR, using invasive coronary angiography and quantitative coronary angiography as the standard of reference; (2) absolute numbers of true positive, false positive, true negative, and false negative results could be derived. Standard meta-analytic methods were applied.

Results

Nine studies with a total of 598 patients with 978 stents included were considered eligible. On average, 9% of stents were unassessable (range 0-42%). Accuracy tests with 95% confidence intervals (CIs) comparing 64-MDCT vs invasive coronary angiography showed that pooled sensitivity, specificity, positive and negative likelihood ratio (random effect model) values were: 86% (95% CI 80-91%), 93% (95% CI 91-95%), 12.32 (95% CI 7.26-20.92), 0.18 (95% CI 0.12-0.28) for binary ISR detection. The symmetric area under the curve value was 0.94, indicating good agreement between 64-MDCT and invasive coronary angiography.

Conclusions

64-MDCT has a good diagnostic accuracy for ISR detection with a particularly high negative predictive value. However, still a relatively large proportion of stents remains uninterpretable. Accordingly, only in selected patients, 64-MDCT may serve as a potential alternative noninvasive method to rule out ISR.     

A bullet wandering through the heart

We report a case of young male with a penetrating chest trauma due to a gunshot. The bullet was detected by conventional X-ray and localized within the lateral wall of the left ventricle by CT. During surgery the bullet was not found. Thereafter conventional X-ray showed migration of the bullet within the lung parenchyma.     

Caloric Restriction and L‐Carnitine Administration Improves Insulin Sensitivity in Patients With Impaired Glucose Metabolism

Background: Reduced circulating and tissue carnitine levels, possibly leading to impaired mitochondrial function, have been postulated to be involved in the pathogenesis of insulin resistance. However, whether L‐carnitine administration may improve insulin sensitivity in patients with impaired fasting glucose (IFG) or type 2 diabetes mellitus (DM‐2) is still controversial. The aim of the study was to explore the role of L‐carnitine supplementation in influencing insulin sensitivity. Methods: A randomized controlled study involving adult outpatients was designed. Adult patients referred to the outpatient clinic and within 10 days of the diagnosis of IFG or DM‐2 were consecutively enrolled. Exclusion criteria were concomitant antidiabetic therapy and modifications of lifestyle during the previous 4 weeks. Patients were randomly assigned to receive a hypocaloric diet for 10 days (group C; n = 8) or the same dietetic regimen in addition to oral L‐carnitine (2 g twice daily) supplementation (group LC; n = 8). Oral glucose tolerance test (OGTT), fasting plasma insulin levels, and homeostasis model assessment of insulin resistance (HOMA‐IR) were assessed at the beginning and end of the study. Data were statistically analyzed using the Student t test for paired and unpaired data. Results: OGTT at 2 hours improved in both groups. Only in the L‐carnitine–supplemented group did plasma insulin levels and HOMA‐IR significantly decrease when compared to baseline values. Conclusions: Considering the role of caloric restriction in increasing the intestinal uptake of carnitine, the results suggest that oral L‐carnitine administration, when associated with a hypocaloric feeding regimen, improves insulin resistance and may represent an adjunctive treatment for IFG and DM‐2.