Inverted-Bearing Reverse Shoulder Arthroplasty: Long-term Survivorship, Complications, Clinical and Radiological Outcomes.

BACKGROUND: Inverted-bearing reverse shoulder arthroplasty (IB-RSA) is characterized by a polyethylene glenosphere and a metallic humeral liner to minimize PE wear and debris secondary to impingement between the humerus and glenoid neck. IB-RSA long-term survivorship, complication and revision rates, as well as clinical and radiographic outcomes have not been reported yet. METHODS: This is a monocentric retrospective study on a consecutive series of 151 patients who underwent primary IB-RSA from January 2009 to September 2015 and were evaluated clinically and radiologically at minimum 8 years follow-up. All complications and reoperations were recorded. Survivorship analysis with any revision surgery as endpoint was done using Kaplan-Meier survival curves. RESULTS: Seventy-eight patients (follow-up rate 51.7%) were reviewed at a mean follow-up of 10.1 ± 1.9 years. At 10 years the revision-free survival was 98.7% (95% CI: 94.8-99.7). Sixteen complications (10.6%) were observed: 2 axillary nerve injuries, 2 infections, 2 glenoid loosenings (which stabilized within one year), 2 cases of otherwise unexplained painful stiffness, 4 acromial fractures, 1 post-traumatic scapular pillar fracture and 3 post-traumatic humeral periprosthetic fractures. Two patients were revised due to infection. No cases of late glenoid loosening and humeral loosening were observed. The revision rate was 1.3%. All the clinical scores and range of motion significantly improved at the last follow-up compared with preoperative status: final Constant score was 66.1 ± 17.4, SSV 79.1 ± 20.9, ASES 82.2 ± 17.7. Scapular notching was observed in 51.4% of patients: only 1 case of grade 3 notching was observed in an early glenoid subsidence case. CONCLUSIONS: Primary IB-RSA appears to be a safe and effective procedure and does not present specific implant-associated complications at long-term follow-up. Radiographic analysis showed that inverting the biomaterials leads to a distinct kind of notching with mainly mechanical features.

Do radiolucent lines and stress shielding of the humeral shaft really matter in shoulder arthroplasty?

The purpose of this study is to evaluate at a mid-term follow up, the radiological survival of an uncemented humeral stem in shoulder arthroplasty. One hundred and twenty-six replacements including hemi (HA), total (TSA) and reverse (RSA) implanted from 1999 to 2008 were reviewed at a mean follow up of 7.2 years (48-144 months). The same uncemented triconical stem (SMR, Lima Corporate) was implanted. There were: 23 HSA, 43 TSA, 60 RSA. An independent observer evaluated all the patients with Constant Score. A radiologic analysis by an expert radiologist and an orthopaedic surgeon was performed: humeral component-bone interface was divided in seven zones. They judged a mobilisation if a migration or tilt of the humeral implant or if≥ 2 mm radiolucent line in at least three zones was present. Chi-squared test, Fisher test and analysis of variance were performed and a p<0.05 was considered statistically significant. No major radiological signs of loosening and no tilt or migration of the humeral component were found. Only 23 (18.2%) patients had no RL around the humeral implant. In the remaining 103 (81.7%) implants: 96 (76.1%) presented RL less than 2 mm, particularly 75 (59.5%) in less than 3 zones and 21 (16.6%) in more than 3 zones. Of the remaining 7 (5.5%) implants the presence of RL of 2 mm or greater in only one zone was seen. Apart from sepsis no revision was performed for humeral component loosening. Although a high rate of RL, uncemented humeral stem has an excellent survivorship at a mid-term follow up. Relationship between presence, position and depth of RL and internal stress shielding is commonly observed but does not appear to compromise quality of fixation or clinical outcomes in shoulder arthroplasty.

Clinical application of MOSkin dosimeters to rectal wall in vivo dosimetry in gynecological HDR brachytherapy.

PURPOSE: Three MOSkins dosimeters were assembled over a rectal probe and used to perform in vivo dosimetry during HDR brachytherapy treatments of vaginal cancer. The purpose of this study was to verify the applicability of the developed tool to evaluate discrepancies between planned and measured doses to the rectal wall. MATERIALS AND METHODS: MOSkin dosimeters from the Centre for Medical Radiation Physics are particularly suitable for brachytherapy procedures for their ability to be easily incorporated into treatment instrumentation. In this study, 26 treatment sessions of HDR vaginal brachytherapy were monitored using three MOSkin mounted on a rectal probe. A total of 78 measurements were collected and compared to doses determined by the treatment planning system. RESULTS: Mean dose discrepancy was determined as 2.2±6.9%, with 44.6% of the measurements within ±5%, 89.2% within ±10% and 10.8% higher than ±10%. When dose discrepancies were grouped according to the time elapsed between imaging and treatment (i.e., group 1: ≤90min; group 2: >90min), mean discrepancies resulted in 4.7±3.6% and 7.1±5.0% for groups 1 and 2, respectively. Furthermore, the position of the dosimeter on the rectal catheter was found to affect uncertainty, where highest uncertainties were observed for the dosimeter furthest inside the rectum. CONCLUSIONS: This study has verified MOSkin applicability to in-patient dose monitoring in gynecological brachytherapy procedures, demonstrating the dosimetric rectal probe setup as an accurate and convenient IVD instrument for rectal wall dose verification. Furthermore, the study demonstrates that the delivered dose discrepancy may be affected by the duration of treatment planning.

A phase III study evaluating the safety and efficacy of NEPA, a fixed-dose combination of netupitant and palonosetron, for prevention of chemotherapy-induced nausea and vomiting over repeated cycles of chemotherapy.

BACKGROUND: Safe, effective and convenient antiemetic regimens that preserve benefit over repeated cycles are needed for optimal supportive care during cancer treatment. NEPA, an oral fixed-dose combination of netupitant, a highly selective NK1 receptor antagonist (RA), and palonosetron (PALO), a distinct 5-HT3 RA, was shown to be superior to PALO in preventing chemotherapy-induced nausea and vomiting after a single cycle of highly (HEC) or moderately (MEC) emetogenic chemotherapy in recent trials. This study was designed primarily to assess the safety but also to evaluate the efficacy of NEPA over multiple cycles of HEC and MEC. PATIENTS AND METHODS: This multinational, double-blind, randomized phase III study (NCT01376297) in 413 chemotherapy-naïve patients evaluated a single oral dose of NEPA (NETU 300 mg + PALO 0.50 mg) given on day 1 with oral dexamethasone (DEX). An oral 3-day aprepitant (APR) regimen + PALO + DEX was included as a control (3:1 NEPA:APR randomization). In HEC, DEX was administered on days 1-4 and in MEC on day 1. Safety was assessed primarily by adverse events (AEs), including cardiac AEs; efficacy by complete response (CR: no emesis, no rescue). RESULTS: Patients completed 1961 total chemotherapy cycles (76% MEC, 24% HEC) with 75% completing ≥4 cycles. The incidence/type of AEs was comparable for both groups. Most frequent NEPA-related AEs included constipation (3.6%) and headache (1.0%); there was no indication of increasing AEs over multiple cycles. The majority of AEs were mild/moderate and there were no cardiac safety concerns based on AEs and electrocardiograms. The overall (0-120 h) CR rates in cycle 1 were 81% and 76% for NEPA and APR + PALO, respectively, and antiemetic efficacy was maintained over repeated cycles. CONCLUSIONS: NEPA, a convenient single oral dose antiemetic targeting dual pathways, was safe, well tolerated and highly effective over multiple cycles of HEC/MEC.

A randomized phase III study evaluating the efficacy and safety of NEPA, a fixed-dose combination of netupitant and palonosetron, for prevention of chemotherapy-induced nausea and vomiting following moderately emetogenic chemotherapy.

BACKGROUND: Antiemetic guidelines recommend co-administration of agents that target multiple molecular pathways involved in emesis to maximize prevention and control of chemotherapy-induced nausea and vomiting (CINV). NEPA is a new oral fixed-dose combination of 300 mg netupitant, a highly selective NK1 receptor antagonist (RA) and 0.50 mg palonosetron (PALO), a pharmacologically and clinically distinct 5-HT3 RA, which targets dual antiemetic pathways. PATIENTS AND METHODS: This multinational, randomized, double-blind, parallel group phase III study (NCT01339260) in 1455 chemotherapy-naïve patients receiving moderately emetogenic (anthracycline-cyclophosphamide) chemotherapy evaluated the efficacy and safety of a single oral dose of NEPA versus a single oral dose (0.50 mg) of PALO. All patients also received oral dexamethasone (DEX) on day 1 only (12 mg in the NEPA arm and 20 mg in the PALO arm). The primary efficacy end point was complete response (CR: no emesis, no rescue medication) during the delayed (25-120 h) phase in cycle 1. RESULTS: The percentage of patients with CR during the delayed phase was significantly higher in the NEPA group compared with the PALO group (76.9% versus 69.5%; P = 0.001), as were the percentages in the overall (0-120 h) (74.3% versus 66.6%; P = 0.001) and acute (0-24 h) (88.4% versus 85.0%; P = 0.047) phases. NEPA was also superior to PALO during the delayed and overall phases for all secondary efficacy end points of no emesis, no significant nausea and complete protection (CR plus no significant nausea). NEPA was well tolerated with a similar safety profile as PALO. CONCLUSIONS: NEPA plus a single dose of DEX was superior to PALO plus DEX in preventing CINV following moderately emetogenic chemotherapy in acute, delayed and overall phases of observation. As a fixed-dose antiemetic drug combination, NEPA along with a single dose of DEX on day 1 offers guideline-based prophylaxis with a convenient, single-day treatment.

Measurements of gamma dose and thermal neutron fluence in phantoms exposed to a BNCT epithermal beam with TLD-700.

Gamma dose and thermal neutron fluence in a phantom exposed to an epithermal neutron beam for boron neutron capture therapy (BNCT) can be measured by means of a single thermoluminescence dosemeter (TLD-700). The method exploits the shape of the glow curve (GC) and requires the gamma-calibration GC (to obtain gamma dose) and the thermal-neutron-calibration GC (to obtain neutron fluence). The method is applicable for BNCT dosimetry in case of epithermal neutron beams from a reactor because, in most irradiation configurations, thermal neutrons give a not negligible contribution to the TLD-700 GC. The thermal neutron calibration is not simple, because of the impossibility of having thermal neutron fields without gamma contamination, but a calibration method is here proposed, strictly bound to the method itself of dose separation.

Online in vivo dosimetry in high dose rate prostate brchytherapy with MOSkin detectors: in phantom feasibility study.

MOSkin detectors were studied to perform real-time in vivo dose measurements in high dose rate prostate brachytherapy. Measurements were performed inside an urethral catheter in a gel phantom simulating a real prostate implant. Measured and expected doses were compared and the discrepancy was found to be within 8.9% and 3.8% for single MOSkin and dual-MOSkin configurations, respectively. Results show that dual-MOSkin detectors can be profitably adopted in prostate brachytherapy treatments to perform real-time in vivo dosimetry inside the urethra.

Solid state TL detectors for in vivo dosimetry in brachytherapy.

In vivo dosimetry provides information about the actual dose delivered to the patient treated with radiotherapy and can be adopted within a routinary treatment quality assurance protocol. Aim of this study was to evaluate the feasibility of performing in vivo rectal dosimetry by placing thermoluminescence detectors directly on the transrectal ultrasound probe adopted for on-line treatment planning of high dose rate brachytherapy boosts of prostate cancer patients. A suitable protocol for TLD calibration has been set up. In vivo measurements resulted to be in good agreement with the calculated doses, showing that the proposed method is feasible and returns accurate results.

Mid-term results of a metal-backed glenoid component in total shoulder replacement.

Total shoulder replacement is a successful procedure for degenerative or some inflammatory diseases of the shoulder. However, fixation of the glenoid seems to be the main weakness with a high rate of loosening. The results using all-polyethylene components have been better than those using metal-backed components. We describe our experience with 35 consecutive total shoulder replacements using a new metal-backed glenoid component with a mean follow-up of 75.4 months (48 to 154). Our implant differs from others because of its mechanism of fixation. It has a convex metal-backed bone interface and the main stabilising factor is a large hollow central peg. The patients were evaluated with standard radiographs and with the Constant Score, the Simple Shoulder Test and a visual analogue scale. All the scores improved and there was no loosening, no polyethylene-glenoid disassembly and no other implant-related complications. We conclude that a metal-backed glenoid component is a good option in total shoulder replacement with no worse results than of those using a cemented all-polyethylene prosthesis.

Boundary lipids in the nicotinic acetylcholine receptor microenvironment.

The structural and functional properties of the nicotinic acetylcholine receptor (AChR), the archetype molecule in the superfamily of Cys-looped ligand-gated ion channels, are strongly dependent on the lipids in the vicinal microenvironment. The influence on receptor properties is mainly exerted by the AChR-vicinal ("shell" or "annular") lipids, which occur in the liquid-ordered phase as opposed to the more disordered and "fluid" bulk membrane lipids. Fluorescence studies from our laboratory have identified discrete sites for fatty acids, phospholipids, and cholesterol on the AChR protein, and electron-spin resonance spectroscopy has enabled the establishment of the stoichiometry and selectivity of the shell lipid for the AChR and the disclosure of lipid sites in the AChR transmembrane region. Experimental evidence supports the notion that the interface between the protein moiety and the adjacent lipid shell is the locus of a variety of pharmacologically relevant processes, including the action of steroids and other lipids. I surmise that the outermost ring of M4 helices constitutes the boundary interface, most suitable to convey the signals from the lipid microenvironment to the rest of the transmembrane region, and to the channel inner ring in particular.

Efficacy of treatment with percutaneous vertebroplasty and kyphoplasty for traumatic fracture of thoracolumbar junction.

AIM: The aim of this paper was to assess the efficacy of a minimally invasive treatment with percutaneous vertebroplasty and kyphoplasty for traumatic fracture of thoracolumbar junction. Treatment of stable traumatic vertebral fractures of the thoracolumbar junction without neurological deficit is still controversy. Conservative treatment, characterized by discomfort and limitation in patient mobility, was progressively replaced by minimally invasive techniques such as percutaneous vertebroplasty and kyphoplasty. METHODS: Between January 2003 and August 2005, 34 patients suffering from 42 thoracolumbar fractures were treated at Neurosurgical Department of Istituto Galeazzi (Milan). The treatment selected (vertebroplasty versus kyphoplasty), depended on age of patients, timing and type of fracture. Results were clinically assessed by Visual Analogue Score (VAS) and Oswestry Disability Index. RESULTS: Mean preoperative VAS was 8.32 (range 5-10). Percutaneous vertebroplasty was performed in 25 cases (73.5%); while 9 patients were treated by kyphoplasty (27.5%); 27 patients showed a single level and 7 multilevel of the fractures. No complications occurred (infection, neurological deficit, embolic events) after treatment. At the early follow-up 91.7% of the patients achieved a good pain control already after 24 hours. Pain relief and disability, analyzed by VAS and Oswestry Disability Index, showed a good results at late follow-up time. CONCLUSIONS: Percutaneous vertebroplasty and kyphoplasty are two safe and effective techniques for treatment of thoracolumbar traumatic fractures and allow a good pain-control and return to normal working activity and social life.

Nitric oxide and iron overload. Limitations of ESR detection by DETC.

The ability of the ESR technique based on diethyldithiocarbamate (DETC) administration was studied as a suitable method to assess NO generation in vivo. The technique was successfully employed to measure NO generation after LPS treatment. DETC2-Fe-NO adducts were detected in liver homogenates of iron overloaded animals. When iron was administered to the animals simultaneously with LPS, NO-dependent signal increased 122%, but the content of NO2- and NO3- in sera was significantly lower (44%) as compared to LPS-treated rats. Iron dextran administration was responsible for a three-fold increase in the DETC2-Fe-NO content in non-LPS treated rats, while NOS activity and sera NO2- and NO3- levels remained unaffected. The adduct generation rate by a chemical NO-source was recorded in the presence of either control or iron overloaded homogenates supplemented with DETC in vivo. The exposure of liver homogenates to NO was performed either by the addition of 1 mM SNAP as NO donor or infusing an aqueous NO solution. In the presence of iron overloaded samples the adduct generation rate was 3.8-4.4-fold higher than in the presence of control samples. This effect restricts the applicability of the method to experimental conditions where iron levels remain constant, therefore it is not suitable for NO generation studies in experimental models where animals were subjected to iron overload.

Hydroxyapatite-coated hip prostheses. Early results from an international study.

A hydroxyapatite-coated hip prosthesis designed to stimulate proximal femoral stress transfer was studied in 222 patients undergoing primary total hip arthroplasty with a minimum followup of 2 years. The femoral component was a roughened titanium alloy with a 50-mu coating of hydroxyapatite applied to the proximal third. A proximal press-fit technique was applied with distal femoral over-reaming as standard procedure. The hydroxyapatite-coated acetabulum was of hemispherical design. Analysis of the clinical results showed a mean Merle D'Aubigné score of 16.7 points at 6 months and 17.4 points at 2 years. Mild residual thigh pain of unknown origin was reported in 3.6% of patients at 2 years. Radiographic evaluation showed complete acetabular and proximal femoral osseointegration without any loosening. No radiolucency or reactive line formation was observed around the hydroxyapatite-coated areas of the prostheses. Femoral bone densification occurred at the coated-uncoated transition zone (54%); 4% to 6% of cases showed cortical hypertrophy at the uncoated area of the stem. Reactive lines were seen around the distal stem in 52% of patients after 2 years. The clinical outcome was excellent, and the radiographic data pointed mainly to proximal femoral stress transfer.

MRI as an adjunct to echocardiography for the diagnostic imaging of cardiac masses.

Nine patients underwent magnetic resonance imaging (MRI) as part of the diagnostic evaluation for cardiac masses; eight of them had been preliminarily studied by 2D-echocardiography (US). MRI did not add to the US diagnostic information in patients affected by intracavitary masses. It represented the definitive diagnostic modality in two patients with intramural pathology: one with ventricular rhabdomyoma, the second with an echinococcyal cyst located within the left atrial wall. The complementary role of MRI to US in cardiac masses is discussed.

[Intracavitary and parietal cardiac measurement with nuclear magnetic resonance: comparison with echocardiography in healthy volunteers]. / Misure endocavitarie e parietali cardiache con risonanza magnetica nucleare: confronto con ecocardiografia in volontari sani.

For quantitative evaluation of cardiac dimensions by Nuclear Magnetic Resonance (NMR), we compared the values obtained by ECG gated NMR with those obtained by two-dimensional echocardiography (2D-echo) in 18 adult healthy volunteers aged 20-40 years (mean 31.6 +/- 5.8). NMR was performed using a 2 T super-conducting magnet operating at 0.5 T with a radiofrequency impulse of 21 MHz. Spin-echo pulse sequences with echo-delay times (TEs) of 30-45 msec were used for data acquisition. The interpulse interval was obtained from the R-R interval on the ECG. Slice thickness was set at 1 cm. To obtain planes oriented along the long axis of the left ventricle similar to 2D-echo, paraxial planes were obtained by double angulation. No significant differences of mean values obtained by NMR and 2D-echo were observed. Regression coefficients were not statistically different from 1 for any of the structures measured: left atrium (y = 1.106x), aorta (y = 1.077x), left ventricle (y = 0.66x), interventricular septum (y = x 1.009x), postero-lateral wall of the left ventricle (y = 1.133x), right ventricle (y = 1.093x). However high coefficients of variation were found for measurement of postero lateral wall (79.5) and interventricular septum (41.4) thicknesses; potential causative factors are discussed.

[3-dimensional automatic dosimetry in curietherapy]. / Dosimetria automatica tridimensionale in Curieterapia.

Isodose curves can be viewed on multiple planes along with the radioactive implant and anatomical structures by projecting them on a video-display. The main options offered are the parallel projection of the implant selecting all the possible rotations, zooming and shifting, calculation of distance between two points of a selected plane, stereoscopic display.