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Reproductive obstacles have led scientists to develop novel techniques/technologies for artificial reproduction. We aimed to investigate the possibility of propagating zebrafish females using sperm ovarian lavage with and without presence of male stimulus. This experiment consisted of several treatments: traditional spawning approaches with females and wild-type males (AB♀ × AB♂); no males present with non-manipulated females (AB♀); no males present with females inseminated with NaCl into ovarian lobes [AB♀(inj.NaCl)]; no males present with females inseminated with sperm from transgenic males into ovarian lobes [AB♀(inj.Tg♂)]; non-manipulated females kept separately from wild-type males (AB♀|AB♂); females kept separately from wild-type males and inseminated with NaCl into ovarian lobes [AB♀(inj.NaCl)|AB♂]; and females kept separately from wild-type males and inseminated with sperm from transgenic males into ovarian lobes [AB♀(inj.Tg♂)|AB♂]. There were no released eggs in both negative control treatments (AB♀ and AB♀|AB♂). Egg production increased (ranged from 0 to 28.5 eggs/female) when females were injected in the presence [AB♀ (inj.NaCl) |AB♂] or absence of male stimulus [AB♀ (inj.NaCl) and (AB♀(inj.Tg♂)]. A further increase in egg production [relative to AB♀, AB♀ (inj.NaCl), and AB♀|AB♂] was detected when females were inseminated with pooled sperm from transgenic males in the presence of male stimulus [AB♀(inj.Tg♂)|AB♂; ranged from 2.5 to 55 eggs/female] or when using traditional spawning approaches (AB♀ × AB♂; ranged from 25 to 131 eggs/female). Females inseminated with sperm produced embryos, although no differences were detected when females were inseminated with pooled sperm from transgenic males in presence (11.8 ± 16.3%) or absence (average = 12.6 ± 9.2%) of male stimulus. Traditional spawning approaches produced the most eggs (81.2 ± 42.3 per female) and highest fertilization rate (81.3 ± 10.4).

CASE: We describe the case of a 53-year-old man who developed acute groin pain 20 days after a posterior L4-L5 interbody fusion. Despite positioning of pedicle screws within the safe zone, an L4 right lumbar artery pseudoaneurysm was found on computer tomography angiogram. Coil embolization was successfully performed. CONCLUSION: Iatrogenic lumbar artery pseudoaneurysms are a rare complication of spinal surgery. Our case is, to the best of our knowledge, the only reported case where this lesion occurred despite good positioning of the screws: It is therefore important to always suspect and exclude this complication in case of suggestive symptoms.

Grade II chronic tibialis posterior tendon dysfunction (PTTD) poses a reconstructive challenge to the orthopaedic surgeon. Aim of this retrospective study is to report the clinical and radiographical results of a case series of 63 patients (102 ft) affected by grade II PTTD who underwent tailored surgical treatment at 10-year mean follow-up. Sixty-three patients (102 ft) were available for clinical and radiological evaluation and were retrospectively reviewed at a mean follow-up of 125.1 ± 14.9 months. Tibialis posterior (PTT) treatment was based on the pathological anatomy of the degenerated tendon. PTT repair was performed in 53 cases. Flexor digitorum longus transfer was performed in the remaining 49. Associated procedures were represented by medial displacement calcaneal osteotomy (MDCO) and lateral column lengthening (LCL) depending on the main clinical feature of the foot (hindfoot valgus and forefoot abduction, respectively). Patients’ evaluation included AOFAS score and radiographic examination with measure of lateral talus-first metatarsal angle (LTFMA) and talo-navicular coverage angle (TNCA). AOFAS hindfoot score was 89 ± 10 points at final follow-up. Eighty-six per cent of the patients declared to be satisfied or satisfied with minor reservations. An overall statistical significant decrease was observed in both LTFMA and TNCA values. A better TNCA correction was observed in case of associated LCL with respect to MDCO. Tailored PTT treatment associated with MDCO or LCL seems provide long-term pain relief and satisfactory function in the treatment of stage II posterior tibial tendon dysfunction.

Introduction: Anterior cruciate ligament (ACL) reconstruction requires an intensive rehabilitation program to be completely successful. Cryotherapy has been described to be helpful in reducing post-operative pain and edema. Aim of this prospective randomized study is to compare two homogeneous groups of patients, one receiving traditional icing regimen and the other a temperature-controlled continuous cold flow device, in post-operative setting after ACL reconstruction. Materials and methods: Forty-seven patients treated for ACL reconstruction using “over the top” technique were enrolled for this study. All patients received the same elastocompressive bandage. Regarding the coolant device, 23 patients were randomized to temperature-controlled continuous cold flow device (Hilotherm® group) and 24 patients were randomized to receive ice bag (control group). The two groups were homogenous for pre-operative (age, sex, and time “lesion to surgery”) and intra-operative parameters (duration of the procedure, meniscectomy, and chondral damage). NRS (numeric rating scale), blood loss, knee volume increase at three established sites, ROM, and pain killers consumption were assessed. The subjective evaluation of the device including practicality and usefulness of the device was investigated. Results: Hilotherm group resulted in lower pain perception (NRS), blood loss, knee volume increase at the patellar apex and 10 cm proximal to the superior patellar pole, and higher range of motion (p

Total knee arthroplasty (TKA) is a widely accepted and successful procedure for end-stage arthritis. Nevertheless, fast-track may be compromised by many factors, such as pain, edema, and blood loss. Cryotherapy has been advocated as a safe and effective strategy to improve the postoperative results, acting on pain, edema, and blood loss. This study is a prospective randomized controlled study, involving 50 patients after primary TKA. A power analysis was performed preoperatively. Twenty-four patients were addressed to a postoperative treatment with a continuous cold flow device (Hilotherm, Hilotherm GmbH, Germany). Twenty-six patients represented the control group, treated with crushed ice packs. All the patients shared the same analgesic strategy and the same rehabilitation protocol. Pain, analgesic consumption, active knee range of motion, drain output, transfusion requirement, and total blood loss were evaluated at different follow-ups (postoperative first, third, and seventh days). The two groups were homogenous for preoperative and intraoperative features. The groups showed no statistically significant differences in all the evaluated parameters. A modest reduction of knee volume was evident after 7 days from surgery (trend). No differences in blood loss were noticed. Continuous cold flow device in the acute postoperative setting after TKA did not show superiority in reducing edema, pain, and blood loss, compared with traditional icing regimen. Thus, due to the costs, it should be reserved to selected cases.

Background: Severe posttraumatic ankle arthritis poses a reconstructive challenge in the young and active patient. Bipolar fresh total osteochondral allograft (BFTOA) may represent an intriguing alternative to arthrodesis and prosthetic replacement. The purpose of this article was to evaluate the outcomes of BFTOA performed through an anterior approach to the ankle and to investigate the parameters influencing the results. Methods: A total of 26 patients (18 males and 8 females with a mean age of 34.9 ± 7.7 years) underwent BFTOA. The allograft was prepared with the help of specifically designed jigs and the surgery was performed using a direct anterior approach. Patients were evaluated clinically and radiographically at 2, 4, 6, and 12 months after the operation, and at a mean 40.9 ± 14.1 months of follow-up. Radiographic evaluation included the measurement of allograft size matching and alignment. Results: The AOFAS score improved from 26.6 ± 6 preoperatively to 77.8 ± 8.7 after a mean follow-up of 40.9 ± 14.1 months ( P < .0005). Six failures occurred. Joint degeneration was classified as 2 in 12 and as 3 in 14 patients. A statistically significant correlation between low degrees of distal tibial slope and better clinical outcomes was observed ( P = .049). Conclusion: BFTOA appears to be a viable option to arthrodesis or arthroplasty. Precise allograft sizing, stable fitting, and fixation and delayed weight-bearing were key factors for a successful outcome. In this series the correct alignment of the tibial graft, in terms of slope, was found to play a crucial role in the allograft survivorship. Level of Evidence: Level IV, case series.

Background: Demoralization syndrome is a significant condition that has not been greatly studied in Southern European countries. Aims: To extend the knowledge of demoralization in Southern Europe by examining its prevalence according to different methods of assessment, its relationship with anxiety and depression, and its impact on quality of life (QoL) among cancer patients. Methods: A convenience sample of 195 cancer outpatients from two oncology centers (102 from Lisbon, Portugal, and 93 from Ferrara, Italy) participated in an observational, cross-sectional study using the Diagnostic Criteria of Psychosomatic Research-Demoralization interview (DCPR/D) and psychometric tools (Demoralization scale-DS; Patient Health Questionnaire-9/PHQ-9; Hospital Anxiety Depression Scale-HADS; and European Quality of Life-5-EQ-5D). Results: A 25.1% prevalence (CI 95%, 0.19-0.31) of clinically relevant demoralization was reported on the DCPR/D interview. A total demoralization score cutoff score ≥ 25 maximized sensitivity (81.6%), and specificity (72.6%) in identifying DCPR/D demoralized patients. The DCPR/D and DS were associated with poorer levels of QoL. About half of the patients who were demoralized were not clinically depressed (PHQ-9). Self-reported suicidal ideation (PHQ-9 item 9) was found in a minority of patients (8.2%), most of whom (77%) were cases of depression (PHQ-9), but one-quarter (23%) were not depressed, yet moderately/severely demoralized (DCPR/D and DS). Conclusions: This Southern European study confirms the importance of demoralization in cancer patients as a different condition with respect to depression and its relationship with poor QoL and suicidal ideation. info:eu-repo/semantics/publishedVersion

Objective:As a part of a European study, we cross-culturally examined the rate of emotional distress and maladaptive coping and their association with cancer patients' satisfaction with their interactions with the physician responsible for their care.Methods:Cancer patients (n = 302) from one Middle European (Austria) and two Southern European (Italy, Spain) countries completed the NCCN Distress Thermometer (DT), the Mini-Mental Adjustment to Cancer (Mini-MAC) Anxious Preoccupation (AP) and Hopelessness (H) sub-scales, and the Physician Patient Satisfaction with Doctors Questionnaire (PSQ).Results:The prevalence of emotional distress (DT caseness) was 60% (26.1% mild, 18.8% moderate, and 14.9% severe distress). Maladaptive coping (Mini-MAC cases) was found in 22.8% (hopeless cases), and 22.5% (anxious preoccupation cases). PSQ-MD was significantly correlated with Mini-MAC/H and Mini-Mac/AP, while PSQ-PS was negatively correlated with Mini-MAC/H. DT cases and those with higher levels of hopelessness reported higher scores on PSQ-MD and lower on PSQ-PS than non-cases. Some differences were found between countries both as far as patients' coping and perception of the interaction with doctors. In hierarchical multiple regression analysis, after adjusting for socio-demographic and medical variables, Mini-MAC/H significantly predicted the scores on PSQ-MD (positive direction) and PSQ-PS (negative direction).Significance of results:The study confirms that about one out of three cancer patients have moderate to high level of emotional distress and about one out of four, clinically significant maladaptive coping. Also, patients showing hopelessness and distress tended to perceive their doctors as both disengaged and less supportive. These results highlights the need for physicians to monitor their patient's level of distress and coping mechanisms and to adjust their own relational and communication style according to patients' psychological condition. Also, cross-cultural issues should be taken into account when exploring psychosocial variables and cancer patients' perception of and satisfaction with the interaction with their doctors.

Background: Multiple-revision anterior cruciate ligament (ACL) reconstructions represent a surgical challenge due to the presence of previous tunnels, hardware, injuries to the secondary stabilizers, and difficulties in retrieving autologous tendons. An anatomic ACL reconstruction may therefore result in a demanding surgery, thus requiring 2 stages. Purpose: To analyze the efficacy of an over-the-top ACL reconstruction technique plus extra-articular plasty using Achilles or tibialis posterior tendon allograft in restoring knee stability in patients with at least 2 failed previous ACL reconstructions, as well as to evaluate the factors able to affect the final outcome. Study Design: Case series; Level of evidence, 4. Methods: From 2002 to 2008, 24 male athletes with a mean age of 30.8 years underwent surgery. Twenty patients had undergone 2, whereas 4 patients had undergone 3 previous reconstructions. The International Knee Documentation Committee (IKDC) score and KT-2000 arthrometric evaluation were used to measure outcomes at a mean follow-up period of 3.3 years (range, 2-7). Results: The mean ± SD IKDC subjective score at follow-up was 81.3 ± 14.0. The IKDC objective score was an A or B in 20 patients (83%). Arthrometer side-to-side difference averaged 3.1 ± 1.1 mm. Range of motion was normal or nearly normal in 23 patients and abnormal in 1. Of the 20 good results, 17 patients resumed sports activity at the preinjury level. Conclusion: A 2-stage revision is an accepted option in cases of excessive tunnel enlargement and bone loss, especially on the femoral side, to achieve anatomic reconstruction. Nonanatomic over-the-top ACL reconstruction and lateral extra-articular plasty technique allow one to overcome difficult anatomic situations on the femoral side, permitting a 1-step surgery. The overall results obtained in this series are comparable with those of other ACL revision series. The higher rate of mild instability observed in our series may not be attributable to the surgical technique but rather to the chronic instability suffered by these knees before last revision.

Background: Chemotherapy-induced nausea and vomiting (CINV) continue to be a distressing problem still reported by cancer patients, with negative consequences on quality of life (QoL). Aims: To prospectively explore the association of psychosocial variables, including emotional distress, maladaptive coping styles and the doctor-patient relationship, with CINV and QoL among cancer outpatients. Methods: A prospective study was conducted on 302 consecutive cancer patients (response rate 80.9%) in Austria, Italy and Spain. The Distress Thermometer (DT), the Mini-Mental Adjustment to Cancer (Mini-MAC), and the Patient Satisfaction with Doctor Questionnaire (PSQ) were used to assess psychosocial variables before chemotherapy. In the 5 days after chemotherapy, CINV was examined by using a daily diary, and the Functional Living Index for Emesis (FLIE) was used to assess QoL. Results: More than half of the patients reported nausea (54%), and a small percentage reported vomiting (14%). CINV had a negative impact on QoL (FLIE caseness, p < 0.01). Maladaptive coping (i.e. hopelessness-helplessness and anxious preoccupation) and emotional distress were associated with CINV (p < 0.05) and poorer QoL (p < 0.05). In logistic regression analysis, nausea was predicted by Mini-MAC/H (OR = 1.1, p = 0.03) and younger age (OR = 0.97, p = 0.04); negative impact on QoL was predicted by grade of chemotherapy emetogenesis (OR = 1.7, p < 0.01) and Mini-MAC/H (OR = 1.2, p = 0.04). Conclusions: Screening and assessment of psychological variables, especially coping, could help in identifying cancer patients at risk for chemotherapy-induced nausea, in spite of the use of antiemetic treatment.

Purpose: Infrapatellar branch of saphenous nerve injury is a common complication following hamstring graft harvest during anterior cruciate ligament reconstruction. The direction of skin incision performed at proximal tibial metaphysis may affect the rate of iatrogenic nerve damage. Aim of the present systematic review was to evaluate evidence that would substantiate the adoption of one incision over another for hamstring graft harvesting. Methods: The available literature was systematically screened searching studies dealing with iatrogenic injury to the saphenous nerve after anterior cruciate ligament reconstruction using hamstring tendons. A search was performed using the keywords “Saphenous” and “Infrapatellar branch” in combination with “Anterior cruciate ligament”, “arthroscopy” and “hamstrings”, supplying no limits regard the publication year. Coleman methodological score was performed in all the retained articles. Results: Five articles matched the inclusion criteria. There were two randomized controlled trials, one prospective comparative study and two retrospective comparative series. Poor methodological quality was found overall. A vertical incision was found to significantly affect the presence of hypoesthesia and the extent of the area of sensory loss in three articles; no difference was registered in one, and a trend towards a lower rate of iatrogenic nerve damage using an oblique incision was found in the remaining one, without any statistical significance. Conclusion: Although the low methodological quality of the analysed studies does not permit to draw definitive conclusions, the anatomical course of the nerve along with the results obtained in the available studies seems to suggest lower rate of neurological impairment adopting an oblique incision. This kind of incision may therefore be preferred in the routine clinical practice. Level of evidence: Systematic review, Level II.

Purpose: Autologous chondrocyte implantation (ACI) in the ankle has become an established procedure to treat osteochondral lesions. However, a non-invasive method able to provide information on the nature of the repair tissue is needed. Recently, MRI T2 mapping was identified as a method capable of qualitatively characterizing articular cartilage. The aim of this study was to evaluate the mid-term results of a series of patients arthroscopically treated by ACI and investigate the nature of the repair tissue by MRI T2 mapping. Methods: Twenty patients, aged 35 ± 8 years, with an osteochondral lesion of the talus, underwent ACI and were evaluated at 5 ± 1 years' follow-up clinically (AOFAS score) and by the MRI T2-mapping sequence. MRI images were acquired using a protocol proposed by the International Cartilage Repair Society, evaluated by the MOCART score and completed by the T2-mapping sequence. Healthy volunteers, mean age 29 ± 6 years, were enrolled, and their T2 map values were used as a control. Their MRI results were then correlated with the clinical score. Results: The AOFAS score increased from 59 ± 16 pre-operatively to 84 ± 18 at follow-up (P < 0.0005). Patients with more than 4 years' follow-up were found to have the most satisfactory results. On the basis of the controls, healthy hyaline cartilage tissue showed a T2 map value of 35-45 ms. A mean T2 map value compatible with normal hyaline cartilage was found in all the cases treated, covering a mean percentage of 69% ± 22 of the repaired lesion area. Conclusions: ACI was able to provide durable results that improved over time. Because of its ability to detect cartilage quality, the MRI T2-mapping sequence integrated with the Mocart score is a valid, non-invasive technique in evaluating the nature of the repair tissue in the ankle joint. Level of evidence: Therapeutic study, Level IV.

Recently the importance of CXCL10 in the pathogenesis of non-segmental vitiligo (NSV) and autoimmune thyroid disorders (AITD) has been shown. No data are present about chemokines CXCL10 (Th1 prototype) and CCL2 (Th2 prototype) circulating levels in NSV patients with/without thyroiditis (AT). Serum CXCL10 and CCL2 have been measured in 50 consecutive NSV patients, in 40 consecutive patients with NSV and AT (NSV+AT), in 50 sex- and age-matched controls without AT (control 1) and in 40 sex- and age-matched patients with AT without NSV (control 2). Serum CXCL10 levels were significantly higher in control 2, than in control 1 (P=0.001; ANOVA). NSV patients have serum CXCL10 levels significantly higher than control 1, or control 2 (P=0.001). NSV+AT patients have serum CXCL10 levels higher than control 1, or 2 (P

Drug malabsorption is one of the potential troubles after bariatric surgery. Evidence for diminished levothyroxine (L-T4) absorption has been reported in patients after bariatric surgery.This study reports 17 cases of hypothyroid patients [who were well replaced with thyroxine tablets (for1 year) to euthyroid thyrotropin (TSH) levels before surgery (13 Roux-en-Y gastric bypasses (RYGB); 4 biliary pancreatic diversions (BPD))]. From 3 to 8 months after surgery, these patients had elevated TSH levels. Patients were then switched from oral tablets to a liquid L-T4 formulation (with the same dosage, 30 min before breakfast).Two-three months after the switch, TSH was significantly reduced both in patients treated with RYGB, as in those treated with BPD, while FT4 and FT3 levels were not significantly changed (RYGB group, TSH μIU/mL: 7.58 ± 3.07 vs 3.808 ± 1.83, P 0.001; BPD group, TSH μIU/mL: 8.82 ± 2.76 vs 3.12 ± 1.33, P 0.01).These results first show that liquid L-T4 could prevent the problem of malabsorption in patients with BPD and confirm those of previous studies in patients submitted to RYGB, suggesting that the L-T4 oral liquid formulation could circumvent malabsorption after bariatric surgery.

Contrasting results have been reported about the prevalence of thyroid autoimmunity (AT) and dysfunction (TD) in patients with psoriatic arthritis (PsA). In this study, we pointed to evaluate the incidence of new cases of clinical and subclinical TD in a broad group of patients with PsA versus a control group, matched by age and gender belonging to the same geographic area. PsA patients with TD were excluded firstly, and new cases of thyroid disorders were evaluated in 97 PsA patients and 97 matched controls, who had comparable iodine intake (median follow-up of 74 months in PsA versus 92 in controls). A raised rate of new cases of hypothyroidism, TD, positive antithyroid peroxidase (AbTPO) antibodies, and appearance of a small hypoechoic thyroid pattern in PsA, especially in female gender, compared to controls has been evidenced. Risk factors in female gender for the development of TD are thyroid-stimulating hormone (TSH) within the normal range but at the higher limit, positive AbTPO, and small thyroid volume. To sum up, thyroid function follow-up and suitable treatments should be performed regularly in female patients at high risk (TSH within the normal range but at the higher limit, positive AbTPO, hypoechoic and small thyroid).

Impaired gallbladder motility is a contributing factor to gallstone formation. Since many drugs delaying intestinal motility inhibit gallbladder emptying, the aim of the present study was to evaluate the effect on gallbladder and sphincter of Oddi motility of a Natural Chestnut Wood Extract (NEC) that reduces intestinal motility. In order to evaluate the effect of the extract in normal- and high-risk gallstone conditions, the investigation was performed using tissues from animals fed normal and lithogenic diet. Fifty guinea pigs were administered either control or lithogenic diet. The spontaneous motility of the gallbladder and sphincter of Oddi were recorded on isolated gallbladder tissues; thereafter, the effect of NEC on motility was tested and compared with carbachol (CCh), potassium chloride (KCl), noradrenaline (NA), and A71623. Compared to controls, the lithogenic diet induced an irregular and disordered motor pattern in both the gallbladder and sphincter of Oddi. NEC increased gallbladder and decreased sphincter of Oddi spontaneous motility independently of cholinergic, adrenergic, and CCK-1 receptor-mediated pathways both in controls and in lithogenic diet-fed animals, although the effect was lower in the latter group. The effect was reversible and mediated by calcium channels. The natural extract of chestnut increasing gallbladder contraction and inducing the relaxation of the sphincter of Oddi can be of benefit in pathological conditions associated with increased transit time at risk of gallstones.

Anterior cruciate ligament (ACL) reconstruction with hamstring graft (HG) is a commonly performed procedure. Despite the type of reconstruction chosen, the detached HG undergoes a remodeling process known as ligamentization. In order to shorten the ligamentization process, the maintenance of HG tibial insertion, aimed to spare the tendons vascular supply, has been postulated. The aim of this paper is to report the results of a prospective randomized study comparing clinical and MRI results between two different ACL reconstructive procedures with and without HG tibial insertion preservation. Forty patients (mean age 27.5 ± 9.5 years) were enrolled and randomly divided into two groups. The study group underwent an ACL reconstruction using a distally inserted HG, while the control group underwent a technique encompassing HG tibial detachment. Subjective and objective IKDC score was administered preoperatively and at 3-, 6-, 12- and 24-month follow-up. Graft morphology was assessed through MRI evaluation performed at 6-month follow-up. Clinical results were excellent in both groups. Regarding MRI results, a better intra-articular graft morphology was observed in the study group (Tau = 0.313, p = 0.024). No differences in graft integration were noticed. The main finding of this preliminary study is that preservation of the hamstring tibial insertion seems to enhance graft ligamentization with improved morphology of the intra-articular portion of the graft compared to a detachment of the hamstring tendons from the tibial side. Further well-designed studies with higher number of patients as well as more serial MRI evaluations are required to validate these preliminary findings.

Background L-thyroxine (L-T4) malabsorption is a potential concern in patients with autoimmune atrophic gastritis. Methods We evaluated five patients with autoimmune gastritis, who showed high serum thyrotropin (TSH) levels (in the hypothyroid range) while in therapy with L-T4 in tablet. All patients were switched to receive an oral L-T4 liquid formulation maintaining the same dosage. Results In all patients who received L-T4 in tablet form after switching to an oral liquid formulation with the same L-T4 dosage, TSH circulating levels were normalized. In four patients who were switched back again to receive L-T4 in tablets, maintaining the dosage, TSH levels worsened again reaching levels in the hypothyroid range. Conclusions The fact that the change from tablets to liquid oral formulation normalised serum TSH levels, and that switching back to tablets caused thyrotropin levels to worsen, leads us to believe that absorption of L-T4 is greater with oral liquid formulations in these patients. These results suggest that the L-T4 oral liquid formulation could circumvent the pH alteration resulting from atrophic gastritis.

Context and Objective: We have studied the antitumor activity of a novel cyclic amide, CLM94, with anti-vascular endothelial growth factor (VEGF) receptor-2 and antiangiogenic activity in primary anaplastic thyroid cancer (ATC) cells in vitro and in vivo. Design and Main Outcome Measures: CLM94 was tested: 1) in two human cell lines (HMVEC-d, dermal microvascular endothelial cells; and 8305C, undifferentiated thyroid cancer) at 0.001–100 μm; 2) in ATC cells at the concentrations of 10, 30, and 50 μm; and 3) in an ATC cell line (AF) in CD nu/nu mice. Results: CLM94 significantly inhibited VEGF receptor-2 and epidermal growth factor receptor phosphorylation in HMVEC-d and proliferation in HMVEC-d and 8305C cells. A significant reduction of proliferation with CLM94 in ATC cells (P < 0.01, ANOVA) and a slight but significant reduction of proliferation with CLM94 30 and 50 μm in normal thyroid follicular cells (P < 0.01, ANOVA) were shown. CLM94 increased the percentage of apoptotic ATC cells dose-dependently (P < 0.001, ANOVA) and inhibited migration (P < 0.01) and invasion (P < 0.001). AF cell line was injected sc in CD nu/nu mice, and tumor masses became detectable 25 d afterward. CLM94 (40 mg/kg · d) significantly inhibited tumor growth (starting 10 d after the beginning of treatment). CLM94 significantly decreased the VEGF-A gene expression in the AF cell line and the VEGF-A protein and microvessel density in AF tumor tissues. Conclusions: The antitumor and antiangiogenic activity of a new “cyclic amide” compound, CLM94, is very promising in ATC, opening the way to a future clinical evaluation.

Background:Arthroscopic treatment of anterior ankle bony impingement provides good results, with a tendency to decrease over time. The purpose of this study was to analyze the factors affecting long-term results.Methods:Eighty consecutive patients with a mean age of 37.3 years were treated between 2000 and 2004. Impingement lesions were identified according to Scranton-McDermott classification. Preoperative ankle osteoarthritis was documented by van Dijk scale upon the x-rays. Bone spurs were analyzed and classified according to location and size. The associated chondral lesions were classified following the International Cartilage Repair Society (ICRS) criteria. Patient data, foot morphology, and previous traumas were recorded. Patients were evaluated after a mean of 104.6 months follow-up with the American Orthopaedic Foot and Ankle Society (AOFAS) scale. The influence of different factors on outcomes was statistically analyzed.Results:The mean preoperative AOFAS score was 50.9, while at follow-up it was 70.7 ( P < .05). The different grades of Scranton-McDermott impingement classification did not affect the results, but the different grades of van Dijk scale significantly affected the result but not the preoperative stage. Tibial localized spurs had better outcome at follow-up. The grade of the chondral lesions significantly affected the outcome. Other factors negatively affecting the results were age, cavus foot morphology, and history of previous ankle fracture.Conclusion:Arthroscopic treatment provides overall good results, but the long-term presence of associated conditions such as chondral lesions, advanced age, and previous trauma are relevant as prognostic factors. Based on these results, a new classification for bony impingement syndrome system is proposed.Level of Evidence:Level IV, case series.

Objective.No study has evaluated circulating chemokine C-X-C motif ligand (CXCL)11 in patients with “mixed cryoglobulinemia and chronic hepatitis C infection” (MC+HCV). We measured CXCL11, and correlated this measurement to the clinical phenotype.Methods.Serum CXCL11, interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α) were assayed in 97 MC+HCV patients and in 97 sex- and age-matched controls.Results.MC+HCV patients showed significantly higher mean CXCL11 serum levels than controls (254 ± 295, 68 ± 16 pg/ml, respectively; p = 0.0002; ANOVA). CXCL11 was significantly increased in 36 cryoglobulinemic patients with compared to those without active vasculitis (303 ± 208 vs 179 ± 62 pg/ml, respectively; p < 0.001; ANOVA). IFN-γ levels were significantly higher in MC+HCV than in controls [6.1 (range 0.8–114.5), 1.4 (range 0.7–2.4) pg/ml, respectively; p < 0.05; Mann-Whitney U test]. Serum TNF-α mean levels were significantly higher in MC+HCV than in controls [13.4 (range 1.8–369), 1.1 (range 0.7–3.2) pg/ml, respectively; p < 0.0001; Mann-Whitney U test]. A multiple regression analysis considering CXCL11 as a dependent variable, and age, alanine aminotransferase, IFN-γ, and TNF-α as independent variables, showed in MC+HCV patients a significant association only with IFN-γ (p < 0.0001).Conclusion.Our study demonstrates markedly high serum levels of CXCL11 in patients with MC+HCV compared to healthy controls overall in the presence of active vasculitis. A strong relationship between circulating IFN-γ and CXCL11 was shown, strongly supporting the role of a T helper 1 immune response in the pathogenesis of MC+HCV.

The association of systemic lupus erythematosus (SLE) and thyroid autoimmunity has been reported by several studies in a wide range of variability. However, from a review of the literature, discrepant results have been reported. The aim of the study was to evaluate the prevalence of clinical and subclinical thyroid disorders in patients with SLE vs sex- and age-matched controls. Thyroid hormones and the presence of antithyroid antibodies were tested and thyroid ultrasonography was performed in 213 patients with SLE vs 426 sex- and age-matched controls, from the same geographic area, with a well-defined status of iodine intake. The odds ratio for subclinical hypothyroidism for female patients with SLE with respect to controls was 4.5 (95% confidence interval [CI], 2.5-8.4); for antithyroid peroxidase antibody (AbTPO) positivity, it was 2.6 (95% CI, 1.7-4.1); and for thyroid autoimmunity, it was 2.9 (95% CI, 2.0-4.4). The mean values of thyroid-stimulating hormone and AbTPO were higher in female SLE patients than in controls (P < .01). A significantly (P < .01) higher prevalence of clinical hypothyroidism and Graves disease was observed in female SLE patients than in controls. No significant difference between SLE patients and controls was detected with regard to free triiodothyronine and thyroxine. In our series, 3% of SLE patients had "nonthyroidal illness syndrome" vs 0 control. Thyroid function and AbTPOs should be tested and ultrasonography should be performed as part of the clinical profile in SLE patients. Subjects at high risk (women, positive AbTPOs, hypoechoic, and small thyroid) should have thyroid function follow-up and appropriate treatment in due course.

The main objective of the study was to evaluate the endocrinological picture of anorexia. The sample consisted of 23 anorectic patients (20 females, 3 males) with a control group of 10 normal females and 5 normal males. All participants underwent a work-up which included testing for hypothalamic, hypophyseal, thyroidal, adrenal, gonadal functioning and glucose metabolism. Our results revealed a reduced urinary output and low serum levels of gonadotropins with different responses to LHRH correlating with the stage of the illness. We found reduced urinary estrogens and elevated testosterone levels in females. Males demonstrated a reduction of testosterone. While basal prolactinemia was normal in both sexes, males showed an exaggerated response to TRH. The thyroid function study in anorectic patients revealed a decrease in T3 and in free T3 and an increase in reverse T3. Free T4 was slightly increased with normal T4 levels. Basal TSH was normal with a delayed peak after TRH. We also noticed in the anorectic population reduced basal glucose levels with a flat glucose curve; reduced insulin levels with a slight increase after glucose administration; elevated basal GH with a fair response to L-Dopa; elevated serum cortisol with loss of circadian rhythm and slightly inhibited by dexamethasone. In addition, both noradrenalin and VMA were reduced. We concluded that the multiple endocrine abnormalities found are consistent with hypothalamic dysfunction. The etiology of this dysfunction remains for the endocrinologist highly controversial.

We studied plasma concentrations of TSH (basal and after TRH), thyroxine (T4), 3,5,3'-triiodothyronine (T3), 3,3',5'-triiodothyronine (reverse T3; rT3), free T4 and free T3 in thirty obese subjects, twenty patients with anorexia nervosa, fifteen malnourished subjects and twenty normal weight subjects. Total serum T4 values were similar for the four groups of subjects while serum free T4 values were slightly increased in anorexia nervosa and normal in the other groups. Serum total and free T3 levels were both significantly decreased in anorexia nervosa and malnutrition, and within normal limits in obesity. The mean serum rT3 level was increased in anorexia nervosa and malnutrition while was reduced in obesity. A delay in peak response of TSH to TRH stimulation (30' rather than 20') was noted in anorexia and malnourished patients. The results suggest that these alterations of serum iodothyronines are due to a different peripheral conversion of T4 to T3 according to nutritional status.

Treatment of partial anterior cruciate ligament (ACL) tears requires ACL remnant preservation. The goal of this study was to compare the outcome of anatomic reconstruction of the torn bundle with nonanatomic augmentation using the over-the-top femoral route. Fifty-two athletes (mean age, 23.3 years) with partial ACL lesions underwent anatomic reconstruction (n=26) or nonanatomic augmentation (n=26). Intraoperative damage of the healthy bundle that required a standard ACL reconstruction occurred in 2 patients in the anatomic reconstruction group. International Knee Documentation Committee (IKDC) score, Tegner score, and arthrometer evaluation were used pre-operatively and at follow-up for up to 5 years postoperatively. One failure occurred in the anatomic reconstruction group. Mean IKDC subjective score at follow-up was 88.2±5.7 in the anatomic reconstruction group and 90.2±4.7 in the nonanatomic augmentation group. According to the IKDC objective score at final follow-up, 96% of knees in the nonanatomic augmentation group were normal vs 87.5% in the anatomic reconstruction group. No significative differences were observed between the 2 groups at final follow-up. Anteromedial bundle reconstruction showed significantly lower IKDC subjective and objective scores and higher residual instability values as evaluated with the arthrometer compared with posterolateral bundle reconstruction ( P =.017). The surgical treatment of ACL partial tears is demanding. Adapted portals, perfect control of the tunnel drilling process, and intercondylar space management are required in anatomic reconstruction. The nonanatomic augmentation technique is simpler, providing excellent durable results over time with a lower complication rate. Anteromedial bundle reconstruction is associated with a poorer outcome, especially when performed with anatomic reconstruction.

Many surgical techniques aimed to obtain an anatomical anterior cruciate ligament reconstruction using the hamstrings tendons are described in the literature. All of these techniques encompass the detachment of the tibial insertion of the hamstrings tendons, thus damaging the neurovascular supply of the tendons and resulting in lower residual proprioceptivity and worse ligamentization of the graft. This article describes a new technique that permits an anatomic single-bundle ACL reconstruction using distally inserted doubled hamstrings tendons fixed at the femoral level with a second-generation cortical suspensory device.

Background: Fresh osteochondral allografts represent a treatment option for early ankle posttraumatic arthritis. Transplanted cartilage survivorship, integration, and colonization by recipient cells have not been fully investigated. The aim of this study was to evaluate the ability of recipient cells to colonize the allograft cartilage and to assess allograft cell phenotype. Methods: Seventeen ankle allograft samples were studied. Retrieved allograft cartilage DNA from fifteen cases was compared with recipient and donor constitutional DNA by genotyping. In addition, gene expression was evaluated on six allograft cartilage samples by means of real-time reverse transcription-polymerase chain reaction. Histology and immunohistochemistry were performed to support molecular observations. Results: Of fifteen genotyped allografts, ten completely matched to the host, three matched to the donor, and two showed a mixed profile. Gene expression analysis showed that grafted cartilage expressed cartilage-specific markers. Conclusions: The rare persistence of donor cells and the prevailing presence of host DNA in retrieved ankle allografts suggest the ingrowth of recipient cells into the allograft cartilage, presumably migrating from the subchondral bone, in accordance with morphological findings. The expression of chondrogenic markers in some of the samples argues for the acquisition of a chondrocyte-like phenotype by these cells. Clinical Relevance: To our knowledge, this is the first report describing the colonization of ankle allograft cartilage by host cells showing the acquisition of a chondrocyte-like phenotype.

Background: A recent one-step arthroscopic technique based on bone marrow–derived cell transplantation has achieved good results in repairing osteochondral lesions of the talus (OLTs), overcoming some of the drawbacks of older techniques. Purpose: To report the results after 4 years of a series of patients who underwent a one-step repair of osteochondral lesions of the talar dome, as well as the capability of magnetic resonance imaging (MRI) using a T2-mapping sequence to predict the clinical outcome. Study Design: Case series; Level of evidence, 4. Methods: Forty-nine patients (age [mean ± SD], 28.08 ± 9.51 y) underwent a one-step repair of OLTs. Patients were evaluated clinically by American Orthopaedic Foot and Ankle Society (AOFAS) scores and radiographs and underwent MRI preoperatively and during postoperative follow-ups at predetermined times. In all patients, the cells were harvested from the iliac crest, concentrated, and loaded on a scaffold that was implanted arthroscopically. Results: The overall AOFAS score (mean ± SD) improved from 63.73 ± 14.13 preoperatively to 82.19 ± 17.04 at 48 ± 6.1 months ( P < .0005), with best results at the 24-month follow-up. A significant decrease in the clinical score was observed between 24 and 36 months postoperatively ( P = .001) and between 24 and 48 months ( P < .005). The T2-mapping analysis showed regenerated tissue with T2 values of 35 to 45 milliseconds, similar to hyaline cartilage, in a mean of 78% ± 16% of the repaired lesion area. The time between the occurrence of trauma and surgery was found to negatively affect the clinical outcome at the latest follow-up; patient’s age and lesion size influenced the early clinical results but did not affect the outcome at final follow-up. The stability of clinical results over time and the percentage of tissue with values similar to hyaline cartilage evidenced by MRI T2 mapping showed a tendency to correlate at the last follow-up ( r = 0.497, P = .06). Conclusion: One-step repair of OLTs had good clinical results that were durable over time, even though there was a slight decrease in AOFAS score at the latest follow-up. The quality of the regenerated tissue detected by MRI T2 mapping directly correlated with the clinical results.

Osteochondral lesions of the talus (OLT) usually require surgical treatment. Regenerative techniques for hyaline cartilage restoration, like autologous chondrocytes implantation (ACI) or bone marrow derived cells transplantation (BMDCT), should be preferred. The aim of this work is comparing two clusters with OLT, treated with ACI or BMDCT. Eighty patients were treated with regenerative techniques, 40 with ACI and 40 with BMDCT. The two groups were homogenous regarding age, lesion size and depth, previous surgeries, etiology of the lesion, subchondral bone graft, final follow-up and pre-operative AOFAS score. The two procedures were performed arthroscopically. The scaffold was a hyaluronic acid membrane in all the cases, loaded with previously cultured chondrocytes (ACI) or with bone marrow concentrated cells, harvested in the same surgical session (BMDCT). All the patients were clinically and radiologically evaluated, using MRI Mocart score and T2 mapping sequence. Clinical results were similar in both groups at 48 months. No statistically significant influence was reported after evaluation of all the pre-operative parameters. The rate of return to sport activity showed slightly better results for BMDCT than ACI. MRI Mocart score was similar in both groups. MRI T2 mapping evaluation highlighted a higher presence of hyaline like values in the BMDCT group, and lower incidence of fibrocartilage as well. To date, ACI and BMDCT showed to be effective regenerative techniques for the treatment of OLT. BMDCT could be preferred over ACI for the single step procedure, patients’ discomfort and lower costs.

BACKGROUND: Osteochondritis dissecans is a relatively common cause of knee pain. The aim of this study was to describe the outcomes of five different surgical techniques in a series of sixty patients with osteochondritis dissecans. METHODS: Sixty patients (age 22.4 ± 7.4 years, sixty-two knees) with osteochondritis dissecans of a femoral condyle (forty-five medial and seventeen lateral) were treated with osteochondral autologous transplantation, autologous chondrocyte implantation with bone graft, biomimetic nanostructured osteochondral scaffold (MaioRegen) implantation, bone-cartilage paste graft, or a "one-step" bone-marrow-derived cell transplantation technique. Preoperative and follow-up evaluation included the International Knee Documentation Committee (IKDC) score, the EuroQol visual analog scale (EQ-VAS) score, radiographs, and magnetic resonance imaging. RESULTS: The global mean IKDC score improved from 40.1 ± 14.3 preoperatively to 77.2 ± 21.3 (p < 0.0005) at 5.3 ± 4.7 years of follow-up, and the EQ-VAS improved from 51.7 ± 17.0 to 83.5 ± 18.3 (p < 0.0005). No influence of age, lesion size, duration of follow-up, or previous surgical procedures on the result was found. The only difference among the results of the surgical procedures was a trend toward better results following autologous chondrocyte implantation (p = 0.06). CONCLUSIONS: All of the techniques were effective in achieving good clinical and radiographic results in patients with osteochondritis dissecans, and the effectiveness of autologous chondrocyte implantation was confirmed at a mean follow-up of five years. Newer techniques such as MaioRegen implantation and the "one-step" transplantation technique are based on different rationales; the first relies on the characteristics of the scaffold and the second on the regenerative potential of mesenchymal cells. Both of these newer procedures have the advantage of being minimally invasive and requiring a single operation.

Purpose: Surgical management of end-stage glenohumeral osteoarthritis represents a challenge in young patients. Bipolar fresh osteochondral allograft (BFOA) represents a fascinating option to prosthetic substitution. Aim of this report is to describe an original technique for BFOA implantation in the shoulder and to describe the clinical and histological results at 30-month follow-up. Methods: A 47-year-old man received BFOA of the shoulder. Clinical and radiographical evaluations were carried out periodically up to 30 months. Results: The clinical score increased from 40 to 78 points (Constant Score), decreased from 64 points to 10 (DASH Disability/Symptom Score) and from 94 points to 0 (DASH Work module Score). Radiographically arthritis and partial reabsorption of the implanted surfaces were evident. Conclusions: The clinical result obtained in this patient seems to support the applicability of BFOA in the shoulder with severe post-traumatic arthritis and with intact rotator cuff. Although unrelated to the clinical result, the occurrence of arthritis of the implanted surfaces is cause of concern. Level of evidence: Case report, Level V.

Purpose: Knee arthrodesis is a scarcely tolerated procedure with a strong negative impact on the quality of life of the patient. The use of a fresh osteochondral allograft represents a fascinating option for a biological joint reconstruction. Aim of this report is to describe a case of total femoral and tibial osteochondral allograft used for reversing a non-tolerated knee fusion in a young patient and to report the clinical and radiographic results obtained at a 4-year follow-up. Methods: A 22-year-old man with right knee arthrodesis received a reversion of the arthrodesis with a total femoral and tibial osteochondral allograft. Clinical and radiographical evaluations were carried out periodically up to 48 months. Results: At 48 months of follow-up, the patient had full integration of the allograft with a range of motion from 0° to 80°. Clinical scores improved from preoperative to final follow-up (IKDC from 25 to 65, KOOS from 32 to 65 and WOMAC from 30 to 74). Radiographic arthritis occurrence of the transplanted surfaces was evident at follow-up. Conclusions: Despite the good clinical results achieved in the case described, a wider applicability of total femoral and tibial osteochondral allograft requires further studies on long-term larger allograft survival. Arthritis recurrence of the transplanted surfaces is cause of concern. Causes and possible solutions need to be more deeply investigated. Level of evidence: Case report, Level V

The aims of this study are to describe evolution in cartilage repair from open field autologous chondrocyte implantation to regeneration by arthroscopic bone-marrow-derived cells (BMDCs) "one step" technique; to present the results of a series of patients consecutively treated and to compare in detail the different techniques used in order to establish the advantages obtained with the evolution in cartilage regenerative methods. 81 patients (mean age 30 ± 8 years) were evaluated in this study. Patient assessment included clinical AOFAS score, X-rays and MRI preoperatively and at different established follow-ups. All the lesions were >1.5 cm 2 and received open autologous chondrocyte implantation (10 cases), arthroscopic autologous chondrocyte implantation (46 cases), and "one step" arthroscopic repair by BMDC transplantation (25 cases). For arthroscopic repair techniques a hyaluronic acid membrane was used to support cells and specifically designed instrumentation was developed. Patients of all the three groups underwent a second arthroscopy with a bioptic cartilage harvest at 1 year follow-up. Mean AOFAS score before surgery was 57.1 ± 17.2 and 92.6 ± 10.5 (P < 0.0005) at mean 59.5 ± 26.5 months. A similar pattern of AOFAS improvement in results was found in the three different techniques. Histological evaluations highlighted collagen type II and proteoglycan expression. The cartilage repair techniques described were able to provide a repair tissue which closely approximates the characteristics of the naive hyaline cartilage. Evolution in surgical technique, new biomaterials and more recently the use of BMDCs permitted a marked reduction in procedure morbidity and costs up to a "one step" technique able to overcome all the drawbacks of previous repair techniques.

Background: Severe post-traumatic ankle arthritis poses a reconstructive challenge in the young and active patient. Bipolar fresh osteochondral allograft (BFOA) may represent an intriguing alternative to arthrodesis and prosthetic replacement. The aim of this study was to describe a lateral trans-malleolar technique for BFOA, and to evaluate the results in a case series. Materials and Methods: From 2004 to 2006, 32 patients, mean age of 36.8 ± 8.4 years, affected by ankle arthritis underwent BFOA with a mean followup of 31.2 months. The graft was prepared by specifically designed jigs, including the talus and the tibia with the medial malleolus. The host surfaces were prepared by the same jigs through a lateral approach. The graft was placed and fixed with twist-off screws. Patients were evaluated clinically and radiographically at 2, 4, and 6 month after operation, and at a minimum 24 months followup. A biopsy of the grafted areas was obtained from 7 patients at 1-year followup for histological and immunohistochemical examination. Results: Preoperative AOFAS score was 33.1 ± 10.9 and postoperatively 69.5 ± 19.4 ( p < 0.0005). Six failures occurred. Cartilage harvests showed hyaline-like histology with a normal collagen component but low proteoglycan presence and a disorganized structure. Samples were positive for MMP-1, MMP-13 and Capsase-3. Conclusion: The use of BFOA represents an intriguing alternative to arthrodesis or arthroplasty. We believe precise allograft sizing, stable fitting and fixation and delayed weightbearing were key factors for a successful outcome. Further research regarding the immunological behavior of transplanted cartilage is needed. Level of Evidence: IV, Retrospective Case Series

Background Ideal treatment of osteochondral lesions of the talus is still controversial. Although good clinical and histologic results have been reported for the knee, long-term results have not been reported for autologous chondrocyte implantation in the ankle. Furthermore, magnetic resonance imaging T2 mapping is becoming an increasingly used method for noninvasive assessment of repair tissue in the knee, but no experience on the ankle has been reported. Hypothesis The 10-year clinical results of autologous chondrocyte implantation in the treatment of osteochondral lesions of the talus has clinical efficacy comparable with the long-term efficacy of autologous chondrocyte implantation in the knee. A secondary hypothesis is that magnetic resonance imaging T2 mapping may provide noninvasive assessment of the repaired tissue quality in the ankle. Study Design Case series; Level of evidence, 4. Methods Between 1997 and 1999, 10 patients (age 25.8 6 6.4 years) with an osteochondral lesion of the talus were treated with autologous chondrocyte implantation. The mean size of the lesions was 3.1 cm2 (range, 2.2-4.3 cm2). All patients were evaluated clinically (American Orthopaedic Foot and Ankle Society score), radiographically, and by magnetic resonance imaging preoperatively and at established intervals up to a mean follow-up of 119 6 6.5 months. At the final follow-up, magnetic resonance imaging was graded with the Magnetic Resonance Observation of Cartilage Repair Tissue scoring system and T2-mapping evaluation in 6 cases. Results Before surgery, the mean American Orthopaedic Foot and Ankle Society score was 37.9 6 17.8 points, while at final follow-up it was 92.7 6 9.9 (P Conclusion The results of autologous chondrocyte implantation in the ankle joint are comparable with those in the knee as demonstrated by the significant clinical improvement, hyaline cartilage repair, and the durability of the results. Integration of both T2 mapping and Magnetic Resonance Observation of Cartilage Repair scoring permitted adequate evaluation of the repair site in the ankle.

The purpose of this study is to (1) report the long-term clinical and radiographic outcomes of a nonanatomical anterior cruciate ligament (ACL) reconstruction using an over-the-top (OTT) femoral route and (2) compare single-strand (1SHG) and double-strand (2SHG) hamstrings graft reconstruction. Fifty-one consecutive patients (mean age, 29.2±3.8 years) underwent nonanatomical ACL reconstruction using OTT femoral passage. Twenty patients underwent 1SHG reconstruction and 31 underwent 2SHG reconstruction. International Knee Documentation Committee (IKDC) score, Knee Injury and Osteoarthritis Outcome Score (KOOS), Tegner score, and KT-1000 (Medmetric Corporation, San Diego, California) evaluation were recorded at a mean follow-up of 12.1±1.6 years. At final follow-up, radiographic evaluation was performed according to the IKDC grading system. Mean IKDC subjective score at follow-up was 76.6±21.9 in the 1SHG group and 88.9±10.0 in the 2SHG ( P =.009). Average KOOS was 82.6±18.7 in the 1SHG group and 92.4±9.2 in the 2SHG group ( P =.016). Objective IKDC evaluation showed a higher percentage of normal knees in the 2SHG group ( P =.018). Pivot shift testing revealed a significantly higher number of normal knees in the 2SHG group ( P =.001). Radiographs showed fewer degenerative changes in the 2SHG group at final follow-up in the medial ( P =.01) and lateral ( P =.037) compartments. Nonanatomical ACL reconstruction using the OTT technique provided satisfactory results in terms of control of both static and dynamic instability at long-term follow-up, thus preventing degenerative joint disease. The 2SHG group showed better subjective and functional outcomes with fewer degenerative changes compared with the 1SHG group at long-term follow-up. [ Orthopedics. 2015; 38(7):e635–e643.]

In this study, we used the affected sibling-pairs approach to investigate the linkage of HLA (human leukocyte antigen)-DRB* with phenotypes related to allergy to Parietaria, the most common pollinosis in Mediterranean countries. The study population consisted of 51 nuclear families (235 subjects). Linkage was detected with Parietaria skin test positivity (p(0.01), presence of IgG and IgE antibodies specific for the major allergen Par o 1 (p0.020 and p0.025, respectively), and absence of Par o 1-specific IgE (p0.020). High levels of Par o 1-specific IgG were associated with DRB1*1101 and/or DRB1*1104 (p0.0001 and p0.0119, respectively) in parents and probands. High levels of Par o 1-specific IgE were associated with DRB*1104 in parents (p0.017) and with DRB1*1101 in probands (p0.0146). When siblings were categorized according to high/low total IgE levels (or =125 IU/ml and125 IU/ml, respectively), high IgE antibody response was associated with DRB1*1104 in siblings with low total IgE (p0.034) and with DRB1*1101 in siblings with high total IgE (p0.05). These results demonstrate that HLA-DRB1*, or genes in linkage disequilibrium, contributes to susceptibility to Parietaria allergy and that total IgE levels can discriminate population subsets where different alleles (at the HLA region or at loci in linkage disequilibrium) contribute to control allergen-specific IgE synthesis.

Autologous chondrocyte implantation (ACI) is an established procedure in the ankle providing satisfactory results. The development of a completely arthroscopic ACI procedure in the ankle joint made the technique easier and reduced the morbidity. The purpose of this investigation was to report the clinical results of a series of patients who underwent arthroscopic ACI of the talus at a mean of 7 ± 1.2-year follow-up.Forty-six patients (mean age 31.4 ± 7.6) affected by osteochondral lesions of the talar dome (OLT) received arthroscopic ACI between 2001 and 2006. Patients were clinically evaluated using AOFAS score pre-operatively and at 12, 36 months and at final follow-up of 87.2 ± 14.5 months.The mean pre-operative AOFAS score was 57.2 ± 14.3. At the 12-month follow-up, the mean AOFAS score was 86.8 ± 13.4 (p = 0.0005); at 36 months after surgery, the mean score was 89.5 ± 13.4 (p = 0.0005); whereas at final follow-up of 87.2 ± 14.5 months it was 92.0 ± 11.2 (p = 0.0005). There were three failures. Histological and immunohistochemical evaluations of specimens harvested from failed implants generally showed several aspects of a fibro-cartilaginous tissue associated with some aspects of cartilage tissue remodelling as indicated by the presence of type II collagen expression.This study confirmed the ability of arthroscopic ACI to repair osteochondral lesions in the ankle joint with satisfactory clinical results after mid-term follow-up.IV, retrospective case series.

No study has evaluated the effect of the peroxisome proliferator-activated receptor γ (PPARγ) agonists on cell viability, proliferation and apoptosis in cultured systemic sclerosis (SSc) fibroblasts.The effects of two pure PPARγ agonists (rosiglitazone and pioglitazone) in cultured SSc fibroblasts were evaluated and compared with effects in normal fibroblasts. The study included evaluation of cell viability and proliferation (based on the cleavage of tetrazolium salts and measurement of absorbance of the cell proliferation reagent WST-1), and determination of cell apoptosis (by means of the Hoechst dye uptake).Rosiglitazone or pioglitazone (20μmolL(-1) ) significantly reduced cell proliferation (cell count of 75% and 83% compared with baseline, respectively, after 2h) and cell viability (absorbance reductions of 25% and 22% compared with baseline, respectively, after 2 h), and increased apoptosis (apoptotic cell percentages 9·9% and 8·6%, respectively, after 48h of incubation) in SSc fibroblasts, whereas they did not present a significant influence on control fibroblasts.The effects of rosiglitazone or pioglitazone shown on SSc fibroblasts raise the hypothesis of a therapeutic role for PPARγ agonists in patients affected by SSc.

No data are available for chemokine (C-X-C motif) ligand 11 (CXCL11), together with CXCL10, circulating levels in autoimmune thyroiditis (AT). We measured serum CXCL11 and CXCL10 in 158 patients with newly diagnosed AT (26% with subclinical hypothyroidism), 56 euthyroid controls, and 20 patients with nontoxic multinodular goiter, all similar in gender distribution and age. CXCL11 was significantly higher in patients with AT (113±56 pg/mL) than in controls (67±16 pg/mL) or patients with multinodular goiter (75±18 pg/mL; P0.0001). Among patients with AT, CXCL11 was significantly higher in those with a hypoechoic ultrasonographic pattern and hypothyroidism. In a multiple linear regression (MLR) model including age, thyroid volume, hypoechogenicity, hypervascularity, thyroid-stimulating hormone (TSH), and anti-thyroid peroxidase, age (P=0.009) and TSH (P0.008) were significantly related to serum CXCL11. In an MLR model of CXCL11 (ln[pg/mL]) versus age, TSH, CXCL10 (ln[pg/mL]), TSH (P=0.028), and CXCL10 (P=0.003) were significantly and independently related to CXCL11. We first show that circulating CXCL11, together with CXCL10, is increased in patients with thyroiditis and hypothyroidism, and is related to CXCL10 levels. These results underline the importance of a Th1 immune attack in the initiation of AT.

99mTC HM-PAO SPECT brain imaging was performed during the headache-free period in 19 young migraineurs, affected by common migraine (CM, 10 cases), classic migraine (CLM, 6 cases) and hemiplegic migraine (HM, 3 cases). SPECT findings were negative in all 10 patients with CM, in 3 cases of CLM and in 2 cases of HM. Positive findings in the remaining 4 patients (3 cases of CLM and 1 of HM) showed a decreased tracer distribution in the temporo-occipital regions (2 cases) and parietal regions (2 cases): the two with decreased temporo-occipital perfusion reported prodromal symptoms exclusively contralateral to the areas of hypoperfusion. An impaired regional cerebral vascular autoregulation may exist even during headache-free intervals in patients suffering from classic and hemiplegic migraine.

Species of the genus Parietaria (pellitory) are a prevalent cause of allergy in the Mediterranean area and the most important in some European regions such as southern Italy and coastal Spain (14, 26, 27, 29, 30, 31, 36, 59, 69). Up to now, however, Parietaria has received little attention in northern Europe and the US because of its limited regional distribution. Therefore, less is known about Parietaria allergy than about other inhalant allergens such as those of grasses, ragweed, and mites. During the last 5 years, only 31 reports on Parietaria allergy have appeared in the literature, as compared with 37 papers on birch pollen. This ratio may appear unbalanced, considering that millions of people suffer from pollinosis caused by Parietaria, while a much smaller number have rhinitis and/or asthma caused by birch pollen. The increasing movement of people throughout Europe and to and from the US is reason to broaden our knowledge of patterns of inhalant allergy in each geographic area, especially where tourism and immigration are high. This paper briefly reviews available data and personal studies on the botanical, aerobiological, immunochemical, and clinical features of Parietaria allergy.

Home care programs for the treatment of frail elderly have been developed in many countries around the world. In the Silver Network project all services are provided in an integrated fashion by one "single entry" center, differently from the traditional fee-for-service or not integrated systems. The delivery of health and social services for frail elderly individuals are integrated and coordinated by a case manager who uses a "second generation" assessment instrument, the Minimum Data Set for Home Care (MDS-HC). We describe the principal clinical and functional characteristics of nearly 1300 patients admitted between 1997 and 1998 to such an integrated home care program in eleven Italian Health Agencies. The database, derived from the serial MDS-HC assessments of each patient, provides a unique opportunity to delineate the different criteria for eligibility for home care, and compare the selected populations of the participating Health Agencies.

Parkinson's disease (PD) is one of the most common neurodegenerative disease characterized by the clinical triad: tremor, akinesia and rigidity. Several studies have suggested that PD patients show disturbances in olfaction at the earliest onset of the disease. The fruit fly Drosophila melanogaster is becoming a powerful model organism to study neurodegenerative diseases. We sought to use this system to explore olfactory dysfunction, if any, in PINK1 mutants, which is a model for PD. PINK1 mutants display many important diagnostic symptoms of the disease such as akinetic motor behavior. In the present study, we describe for the first time, to the best of our knowledge, neurophysiological and neuroanatomical results concerning the olfactory function in PINK1 mutant flies. Electroantennograms were recorded in response to synthetic and natural volatiles (essential oils) from groups of PINK1 mutant adults at three different time points in their life cycle: one from 3-5 day-old flies, from 15-20 and from 27-30 days. The results obtained were compared with the same age-groups of wild type flies. We found that mutant adults showed a decrease in the olfactory response to 1-hexanol, α-pinene and essential oil volatiles. This olfactory response in mutant adults decreased even more as the flies aged. Immunohistological analysis of the antennal lobes in these mutants revealed structural abnormalities, especially in the expression of Bruchpilot protein, a marker for synaptic active zones. The combination of electrophysiological and morphological results suggests that the altered synaptic organization may be due to a neurodegenerative process. Our results indicate that this model can be used as a tool for understanding PD pathogensis and pathophysiology. These results help to explore the potential of using olfaction as a means of monitoring PD progression and developing new treatments.

SYNOPSIS Electronic pupillometry before and after phenylephrine instillation in the right eye was carried out in 18 children aged 10 to 16 years suffering from recurrent abdominal pain (RAP) and 15 age-matched controls. Before stimulation the pupillary diameter was almost equal in the two groups. After phenylephrine eye drops iris dilatation was greeter in RAP patients than in controls, even though the difference was not statistically significant. These results seem to suggest children with RAP have a chronically disturbed receptor sensitivity in their iris neuromuscular junction caused by a sympathetic hypofunction, similar to that already reported in migrainous patients.

An 8-month, double-blind, placebo-controlled crossover trial was carried out on the use of nimodipine in migraine prophylaxis in 37 patients aged 7 to 18 years old. After a 4-week medication-free run-in period, 19 subjects (Group 1) received a placebo while 18 (Group 2) received nimodipine (10-20 mg t.i.d., according to body weight), for 12 weeks. After a 4-week wash-out period, the groups switched therapy for a further 12 weeks. 30 patients completed the trial and the number of dropouts was comparable in the 2 groups. The only side-effect during nimodipine treatment was mild abdominal discomfort (3 cases). The treatments were evaluated on the basis of frequency and duration of attacks. There was a significant reduction in both parameters during the first period of treatment. During the second period of treatment, nimodipine proved to have a significantly greater effect than the placebo with regard to frequency, whereas the response was similar with the placebo as regards duration of attacks. The latter parameter shows a significant decrease during the treatment periods, regardless of type of therapy.

We evaluated the behavior of serum cationic trypsinogen (SCT), an enzyme of solely pancreatic origin, in 30 patients with chronic pancreatitis and 25 healthy subjects as a control, after secretin and bombesin stimulation. After both the stimulations, serum cationic trypsinogen is unable to distinguish between the healthy control subjects and the patients with chronic pancreatitis. On the other hand, after secretin, the enzyme is able to separate chronic pancreatitis patients with different levels of exocrine function insufficiency. It does so with a greater statistical significance than that obtained by the rapid injection of bombesin and equal to that of trypsin into the duodenal juice during duodenal intubation. For these reasons, as well as the absence of any side-effects, secretin is preferred to bombesin stimulation in the evaluation of the exocrine pancreatic function in patients with chronic pancreatitis.

Using radioimmunoassay, we tested serum elastase 1 (E1), an enzyme secreted only from the pancreas, in 200 subjects as follows: 39 healthy subjects as controls, 56 patients with diseases of the digestive tract, 66 patients with hepatobiliary diseases, and 39 patients with pancreatic diseases. The serum E1 showed high specificity and proved very useful in the diagnosis of acute pancreatitis. However it was not useful in diagnosis of clinically silent chronic pancreatitis, nor in its functional evaluation. On the other hand, it was found to be a valuable guide in revealing a concomitant pancreatic pathology during hepatobiliary diseases. Further investigation is needed of the behavior of E1 in patients who have undergone a total pancreatectomy, where the enzyme remains measurable, and in those with an ileocolic disease in an acute phase where E1 is increased in many patients.

Sulbactam is a new beta-lactamase inhibitor with pharmacokinetic characteristics in humans similar to those of ampicillin. A total of 41 patients hospitalized in the Clinic of Infectious Diseases, University of Naples, for chronic liver diseases, were treated with sulbactam/ampicillin (ratio 1:2) for urinary, respiratory, biliary tract or soft tissue infections. Sulbactam/ampicillin was administered im or iv at a dosage of 3-9 g/day depending on the site and severity of the infection. All the patients treated with sulbactam/ampicillin had clinical signs and symptoms of infection, and all the organisms isolated were sensitive to sulbactam/ampicillin (MIC less than 16 mg/l). For both Gram-positive and Gram-negative bacteria the sulbactam/ampicillin MICs were much lower than the ampicillin MICs. In agreement with the favourable in-vitro results, we observed good therapeutic efficacy. 85% of the patients recovered or improved within a few days of therapy, with no clinical relapses, and in 81% of the infections the responsible bacteria were completely eradicated. We observed a low number of side effects (3/41 oral candidosis; 3/41 pain at the im injection site) and no change in the blood chemistry tests.

We have evaluated the serum changes of trypsin, pancreatic isoamylase and lipase, after rapid infusion of secretin, in 45 patients with chronic pancreatitis compared with 35 healthy control subjects. On the basis of duodenal intubation results, chronic pancreatitis patients were divided into two subgroups at different levels of functional impairment. Using the peak activities of the enzymes we have been able to separate the two chronic pancreatitis subgroups by statistical difference; only trypsin distinguishes healthy control subjects from mild to moderate chronic pancreatitis. Therefore, we propose to put into clinical practice this serum provocative test to evaluate the functional damage of an established chronic pancreatitis.