Mid-term clinical and radiographic outcome of metal-on-metal hip resurfacing through an anterolateral approach.

PURPOSE: The aim of this retrospective study was to evaluate the medium-term clinical and radiographic results of current generation metal-on-metal resurfacing prostheses performed through anterolateral approach. MATERIALS AND METHODS: Fifty-seven hips in 52 patients underwent resurfacing arthroplasty. Two patients died from unrelated causes, leaving 55 hips in 35 males (3 bilateral) and 15 females (2 bilateral), with a mean age at surgery of 56.2 years (range, 27-70 years). Clinical and radiographic assessment was carried out preoperatively and at follow-up in all the survived cases. The cumulative survival rate was determined according to the method of Kaplan-Meier. RESULTS: At a mean follow-up of 5.2 years (range, 1.8-9.1 years), 2 HRs of the same female patient were revised because of early loosening of the acetabular component. Deep venous thrombosis and transient femoral nerve palsy occurred both in 1 case. No specific complications of HR were observed. Average Harris hip score improved significantly from 59.8 points (range, 30.4-90.6) preoperatively to 93.7 points (range, 53-100) at the latest examination. Neck narrowing showed an average of 3.27%, but it never exceeded 10%. Nonprogressive acetabular radiolucencies and osteolysis were detected both in 2 hips. A high rate of patients (32, 60.4%) developed heterotopic ossifications, although low-grade in most cases (27, 84.4%). The cumulative survival rate at 9.1 years with revision for any reason as the end point was 93.0%. CONCLUSIONS: The early clinical and radiographic results of modern metal-on-metal hip resurfacing performed through an anterolateral approach are promising, but longer-term follow-up studies are necessary.

Consensus clustering methodology to improve molecular stratification of non-small cell lung cancer.

Recent advances in machine learning research, combined with the reduced sequencing costs enabled by modern next-generation sequencing, paved the way to the implementation of precision medicine through routine multi-omics molecular profiling of tumours. Thus, there is an emerging need of reliable models exploiting such data to retrieve clinically useful information. Here, we introduce an original consensus clustering approach, overcoming the intrinsic instability of common clustering methods based on molecular data. This approach is applied to the case of non-small cell lung cancer (NSCLC), integrating data of an ongoing clinical study (PROMOLE) with those made available by The Cancer Genome Atlas, to define a molecular-based stratification of the patients beyond, but still preserving, histological subtyping. The resulting subgroups are biologically characterized by well-defined mutational and gene-expression profiles and are significantly related to disease-free survival (DFS). Interestingly, it was observed that (1) cluster B, characterized by a short DFS, is enriched in KEAP1 and SKP2 mutations, that makes it an ideal candidate for further studies with inhibitors, and (2) over- and under-representation of inflammation and immune systems pathways in squamous-cell carcinomas subgroups could be potentially exploited to stratify patients treated with immunotherapy.

Bronchoscopy in times of COVID-19 pandemic: An interventional pulmonology unit experience.

Coronavirus disease 2019 (COVID-19) is an acute respiratory disease that has rapidly spread to become a global pandemic. Bronchoscopy is clearly a high-risk manoeuvrer, so to continue endoscopic activity safely it was necessary to make many changes. We created different ways to access and exit the endoscopy theatre and reinforced our dressing/undressing regimens as well as equipment cleaning techniques. To prevent aerosol dispersion we used a bag valve mask with an antibacterial-antiviral filter, introducing the flexible bronchoscope orally rather than through the nose. For procedures with increased contagious risk a nasopharyngeal swab was required. From the date of the first case of COVID-19 in our hospital to December 31 2020, we performed 1027 bronchoscopies, in both negative and positive patients. No outbreaks occurred within the staff and no patients are known to have developed COVID-19 after a procedure. Our experience underscores how it is possible to continue endoscopic activity safely.

Protease inhibitors elicit anti-inflammatory effects in CF mice with Pseudomonas aeruginosa acute lung infection.

Pseudomonas aeruginosa is the major respiratory pathogen in patients with cystic fibrosis (CF). P. aeruginosa-secreted proteases, in addition to host proteases, degrade lung tissue and interfere with immune processes. In this study, we aimed at evaluating the possible anti-inflammatory effects of protease inhibitors Marimastat and Ilomastat in the treatment of P. aeruginosa infection. Lung infection with the P. aeruginosa PAO1 strain was established in wild-type and cystic fibrosis transmembrane conductance regulator (CFTR) knock-out C57BL/6 mice expressing a luciferase gene under control of bovine interleukin (IL)-8 promoter. After intratracheal instillation with 150 µM Marimastat and Ilomastat, lung inflammation was monitored by in-vivo bioluminescence imaging and bacterial load in the lungs was assessed. In vitro, the effects of protease inhibitors on PAO1 growth and viability were evaluated. Acute lung infection was established in both wild-type and CFTR knock-out mice. After 24 h, the infection induced IL-8-dependent bioluminescence emission, indicating lung inflammation. In infected mice with ongoing inflammation, intratracheal treatment with 150 µM Marimastat and Ilomastat reduced the bioluminescence signal in comparison to untreated, infected animals. Bacterial load in the lungs was not affected by the treatment, and in vitro the same dose of Marimastat and Ilomastat did not affect PAO1 growth and viability, confirming that these molecules have no additional anti-bacterial activity. Our results show that inhibition of protease activity elicits anti-inflammatory effects in cystic fibrosis (CF) mice with acute P. aeruginosa lung infection. Thus, Marimastat and Ilomastat represent candidate molecules for the treatment of CF patients, encouraging further studies on protease inhibitors and their application in inflammatory diseases.

Invasive slug Meghimatium pictum (Stoliczka, 1873) infected by Angiostrongylus costaricensis Morera & Céspedes, 1971, and the possible risk of human infection associated with grape consumption.

Many molluscs may be infected with angiostrongylid larvae. Following the histopathological diagnosis of abdominal angiostrongyliasis in a grape farmer from southern Brazil, molluscs in the area were investigated. During a nocturnal search, 245 specimens of slugs were collected and identified as the invasive Chinese slug Meghimatium pictum. Angiostrongylus costaricensis worms were recovered from mice that were experimentally infected with larvae obtained from 11 (4.5%) of the molluscs. This study presents the first report of M. pictum being identified as an intermediate host for A. costaricensis. Most of the slugs were collected from grape plants, which suggests that transmission may be associated with grape consumption.

High-dose enoxaparin in the treatment of abdominal angiostrongyliasis in Swiss mice.

Abdominal angiostrongyliasis (AA) is caused by Angiostrongylus costaricensis, which inhabits mesenteric arteries. There is no drug treatment for AA, and since intestinal infarction due to thrombi is one of the main complications of the disease, the use of anticoagulants may be a treatment option. Thus, we aimed to assess the effect of high doses of enoxaparin on the prevention of ischaemic intestinal lesions and on the survival of mice infected with A. costaricensis. Twenty-four mice were infected with L3 of A. costaricensis and divided equally into two groups: Group 1, control treated with placebo, and Group 2, treated daily with enoxaparin (2.5 mg/kg) for 50 days. All mice were subjected to necropsy and histological analysis. The results from gross and microscopic assessments showed no variation in the prevalence of lesions between the groups. An analysis was also performed among survivors and non-survivors, showing that animals that died often presented lesions, such as granulation tissue in the serosa, and intestinal infarction and adhesion. The mortality rate did not vary between the enoxaparin-treated and control groups. Thus, we showed that high doses of enoxaparin have no protective effect against AA, as the survival rates and lesions of mice did not vary between the treated and control groups. Considering that the use of prophylactic doses was also shown to be ineffective in a previous study, we do not recommend the use of enoxaparin for AA treatment.

Chromium-induced diffuse dermatitis with lymph node involvement resulting from Langerhans cell histiocytosis after metal-on-metal hip resurfacing.

Total hip arthroplasty (THA) is a highly effective surgical treatment for severe joint involvement. However, due to the release of metal ions in the blood, the patients who undergo hip replacement with metal-on-metal (MOM) bearings may develop signs of allergic skin disease. We report a case of a 60-year-old man who had received MOM hip resurfacing 5 years earlier for osteoarthritis. He presented with a 3-year history of diffuse dermatitis that did not respond to antihistamines and corticosteroids and also had elevated serum levels of chromium and cobalt. A patch test revealed chromium-sulfate hypersensitivity. A skin biopsy showed nonspecific perivascular lymphocytic infiltrate associated with histiocytes. A biopsy of an inguinal lymph node demonstrated large aggregates of Langerhans cells, suggesting type IV delayed-type hypersensitivity. The prosthesis was replaced using ceramic-on-ceramic bearings and the dermatitis resolved after 3 months. The lymph nodes decreased in volume and the serum chromium levels normalized within 24 months of revision surgery. The high levels of serum ions associated with the metal debris from MOM-THAs may induce sensitization and type IV hypersensitivity reactions. Replacing the prosthesis using alternative coupling surfaces is the only approach that has the capacity to resolve these symptoms. Physicians who are not familiar with this issue may misdiagnose systemic symptoms and provide inadequate treatment.

[Diclofenac: update on tolerableness and spinal anti-inflammatory action]. / Diclofenac: novità su tollerabilità ed azione antinfiammatoria spinale.

The non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely used drugs in the control of postoperative pain. In choosing the NSAID to be used, it is essential to assess the most favorable risk/benefit ratio according to a careful assessment of intrinsic and extrinsic risk factors and cardiovascular, gastrointestinal, renal and metabolic patient comorbidities. Diclofenac dose of 150 mg/die is the NSAID that has wider literature that attests its efficacy and tolerability. Due to its high lipid solubility, it is one of the few NSAIDs that are able to cross the blood-brain barrier, with an action principally directed towards COX-2. Over time, several studies have been conducted to evaluate the side effects of NSAIDs. Regarding Diclofenac's cardiovascular and gastrointestinal tolerability, recent studies indicate that the relative risk and absolute risk of complications of Diclofenac are similar to COXIB and inferior to other NSAIDs. Important feature of Diclofenac is that, unlike other NSAIDs, it does not interfere with the cardio-protective effect of acetyl-salicylic acid. Diclofenac potassium is instead indicated for use as an analgesic in headache and as an antipyretic in influenza-like symptoms. Studies with the aim of investigating the intestinal damage exacerbated by proton pump inhibitors drugs, when associated with NSAIDs, state that at least in part, they aggravate the intestinal damage induced by NSAIDs due to significant changes in intestinal microbial populations. The reference dose of Diclofenac used in all randomized controlled trials is 150 mg/die; this controlled release dosage allows to decrease the number of daily administrations, ensuring a better patient compliance, especially if elderly and/or in polytherapy.

Efficacy of fleece-bound sealing system (TachoSil®) in delayed anterior tracheal lacerations secondary to ischemic tracheal necrosis after total thyroidectomy.

Thyroidectomy is one of the commonest surgical operations performed in endocrine surgery; results are generally excellent and morbidity and mortality usually are negligible. Total thyroidectomy's complication rates are low, with an overall incidence of 4.3% among experienced surgeons: the most frequent complications are vocal cord paresis or paralysis, hypoparathyroidism, hypocalcemia, haematoma and wound infection. Tracheal injury following thyroidectomy is even more rare. As reported from some authors, inadvertent tracheal injury has an incidence of 0-0.6% during thyroidectomy. Tracheal laceration (generally located in the posterolateral surface) is often recognized and repaired immediately, during the same intervention. Rarely, following a total thyroidectomy, a delayed tracheal rupture may occur secondary to an ischemic damage of the trachea. This has been described in few cases reported in literature. In this paper we report of a case in which delayed tracheal lacerations appeared 10 days after the patient underwent total thyroidectomy: a prompt surgical operation was efficient using both direct sutures of tracheal breaches and a patch of fibrinogen-thrombin coated collagen fleece covering the entire surface.

Femoral revision with the Wagner tapered stem: a ten- to 15-year follow-up study.

Revision after failed femoral components may be technically demanding due to loss of peri-prosthetic bone. This retrospective study evaluated the long-term results of femoral revision using the cementless Wagner Self-Locking stem. Between 1992 and 1998, 68 consecutive hips in 66 patients underwent femoral revision using this implant. A total of 25 patients died from unrelated causes without further revision; the remaining 41 hips in 41 patients (12 men and 29 women) with a mean age of 61 years (29 to 80) were reviewed at a mean follow-up of 13.9 years (10.4 to 15.8). A transfemoral approach was used in 32 hips. A total of five stems required further revision because of infection in two, progressive subsidence in two and recurrent dislocation in one. Four hips had dislocated and eight stems had subsided ≥ 10 mm. The mean Harris hip score improved from 33 points pre-operatively to 75 points at final follow-up (p < 0.001). In all, 33 stems (91.7%) showed radiological signs of stable bone fixation. The cumulative survival rates at 15.8 years with femoral revision for any reason and for stem failure as the endpoints were 92.0% (95% confidence interval (CI) 86.0% to 98.4%) and 96.6% (95% CI 92.2% to 100%), respectively. The survivorship with revision and ≥ 10 mm migration of the stem as the endpoint was 83.6% (95% CI 76.6% to 91.4%). This study shows quite good survival and moderate clinical outcome when using a monoblock tapered titanium stem for supporting the regeneration of bone in complex revision hip surgery.

Preliminary results of a new small-bore percutaneous pleural catheter used for treatment of malignant pleural effusions in ECOG PS 3-4 patients.

BACKGROUND: In cancer patients with malignant pleural effusions(MPEs),the commonest procedure to treat them with palliative intention is talc pleurodesis (TP) which can be obtained with talc slurry (TS) using small-bore catheters(SBC)or with thoracoscopic poudrage. SBC use is therefore rapidly increasing. The aim of this paper is to present our preliminary TP results using a new percutaneous chest drainage system(UNICO®, Redax, Mirandola Modena, Italy). METHODS: In the period 1st March-20th of July 2011,seven consecutive ECOG PS 3-4 patients(4 females, mean age 73.2 ± 12.1 years),unfit for thoracoscopic talc poudrage, were enrolled in our study. All patients received many thoracentesis before the placement of a chest drainage(median thoracentesis number:4.42 ± 1.13).UNICO® was bedside placed in all cases and TS was administered through the drainage when the overall fluid amount didn't exceed 150-200 ml/24 h and the lung was correctly re-expanded at the chest X-ray control. RESULTS: There were no clinical complications following the placement of the drainage: its placement was easy, safe and well-tolerated by all patients. The median chest tube stay, before TS, was 7.2 ± 2.7 days while the median chest tube stay after TS was 1.5 ± 0.7 days. A satisfactory radiological lung expansion was achieved in all cases; PL effectiveness and dyspnea relief were complete in 6 and 4 cases, respectively. No patients required any further thoracentesis. CONCLUSIONS: TS through UNICO® is safe and efficient. The drainage was well-tolerated by all patients, even in case of its long-term stay. We may conclude that bedside TS through this new small-bore percutaneous drainage should be proposed as a viable clinical solution for MPEs in ECOG PS 3-4 patients, unfit for a thoracoscopic procedure. Moreover, with this device, we believe that TS might be an accessible procedure for pulmonologists and oncologists too.

Combined radiofrequency and kyphoplasty in painful osteolytic metastases to vertebral bodies.

PURPOSE: The aim of this study was to assess retrospectively the safety and efficacy of combined radiofrequency (RF) and kyphoplasty (KP) in managing painful osteolytic metastases to vertebral bodies resistant to conservative treatments. MATERIALS AND METHODS: Eleven patients (9 women and 2 men; mean age 68 years; age range 58-82) with painful osteolytic vertebral body metastases unresponsive to conservative treatments underwent RF combined with KP under general anaesthesia. Primary neoplasms were kidney carcinoma (n=1), breast carcinoma (n=1), thyroid carcinoma (n=2) and multiple myeloma (n=7). Lesion levels were cervical (n=1), thoracic (n=9) and lumbar (n=1). Combined RF and KP was well-tolerated by all patients. The procedures were performed using fluoroscopic guidance and intraoperative neurophysiology monitoring. Pain relief with the visual analogue scale (VAS) pain score and analgesic consumption were evaluated before and after treatment. RESULTS: No complication occurred. In one case, we observed an asymptomatic cement leakage. Pain significantly decreased after treatment: the mean VAS pain score before treatment was 8 (range 7-10) vs. 1.8 (range 0-3) and 1.9 (range 1-3), respectively, 72 h and 6 weeks after the treatment. Analgesic reduction was achieved in all patients. CONCLUSIONS: RF combined with KP represents a potential alternative method for palliation of painful spinal osteolytic metastases in selected patients. The procedures are safe and provide pain relief with bone augmentation and improvement in quality of life.

Treatment of type-A3 amyelic thoracolumbar fractures (burst fractures) with kyphoplasty: initial experience.

The authors propose a minimally invasive procedure for treating type-A3 amyelic thoracolumbar fractures according to Magerl classification (compression burst fractures). The procedure, percutaneous kyphoplasty, allows the fracture to be reduced and vertebral height to be restored by injecting bone cement into a cavity created in the vertebral body by an inflatable balloon introduced with the percutaneous approach. Four patients were successfully treated, with clinical and functional benefit in all cases. There were no complications.

Internal femoral osteosynthesis after external fixation in multiple-trauma patients.

In this study the authors evaluate the results of internal synthesis of femoral fractures in polytraumatised patients initially treated by external fixation (EF). From January 2002 to December 2005, 39 femurs in 37 polytraumatised patients (average age 34.2 years, range 18-44) with closed fractures and an ISS>20 were initially treated with EF. There were three groups: Group A, 13 cases when conversion to internal osteosynthesis occurred after 4-7 days (average 5.6 days); Group B, 11 cases with a 4-6-month interval before internal osteosynthesis, and after investigation using MRI and scintigraphy with labelled leucocytes; Group C, the remaining cases treated definitively with EF. Time of healing, lower limb function, time of return to previous activities and short and long-term complications were evaluated at the follow-up. The average time of follow-up was 23 months. In Group A the time of bone healing was 123 days; there were no events of embolism but one case of pseudoarthrosis and one case of instrument failure. In Group B the time of bone healing was 274 days, with one case of pseudoarthrosis and one case of deep infection. In Group C the average healing time was 193 days, with 3 cases of screw (half-pin) osteolysis. Functional recovery was delayed by the presence of other fractures. EF is a simple, quick and safe procedure to stabilise fractures in polytraumatised patients. According to damage control orthopaedic (DCO) concepts, it is possible to replace EF with internal synthesis after an interval as this reduces the risks of internal osteosynthesis when performed in the emergency period. EF can also be maintained as definitive treatment but should a change to internal synthesis be needed, it is possible to do it safely after excluding bone infection.

Mortality from second tumour among long-term survivors of retinoblastoma: a retrospective analysis of the Italian retinoblastoma registry.

Survivors of retinoblastoma (Rb) are at high risk of dying from second malignant tumour. The occurrence of second malignant neoplasm (SMN) and related mortality in a cohort of 1111 cases from the Italian Retinoblastoma Registry was analysed, considering the possible role of both genetic and iatrogenic causes. Rb patients had a greater than 10-fold excess in overall mortality compared with the general population (standardized mortality ratio (SMR) 10.73, 95% CI 9.00-12.80). Their excess risk attributable to cancers other than Rb was 14.93 95% CI 10.38-21.49). Survivors of hereditary Rb had an SMR for all causes of 16.25 (95% CI 13.20-20.00), whereas their SMR for all cancers was 25.72 (95% CI 17.38-38.07). Survivors of unilateral sporadic Rb had an SMR of 4.12 from all cancers (95% CI 1.55-10.98) and a much higher excess for overall mortality (SMR 13.34, 95% CI 10.74-16.56). As expected, survivors of hereditary Rb had higher mortality from cancers of the bone (SMR 391.90, 95% CI 203.90-753.20) and soft tissue (SMR 453.00, 95% CI 203.50-1008.40), small intestine (SMR 1375.50, 95% CI 344.00-5499.70), nasal cavity (SMR 13.71, 95% CI 1.93-97.35) and cancers of the brain and central nervous system (SMR 41.14, 95% CI 13.2-127.55).

Diffuse and focal brain stem tumors in childhood: prognostic factors and surgical outcome. Experience in a single institution.

OBJECTIVE: Brainstem tumors (BSTs) are usually gliomas and are divided into diffuse BSTs (DBSTs) and focal BSTs (FBSTs). The aim of this study is to investigate the different outcomes of these two entities. METHODS: Thirty-one patients with BSTs were admitted to our institution from 1995 to 2003. Patients with DBSTs were treated with locoregional radiotherapy (1.8 Gy/day for 54 Gy) and weekly vincristine for radiosensitization (1.5 mg/sm for six total doses). Patients with FBSTs underwent surgical resection. Chemotherapy and/or radiotherapy were considered in progression. RESULTS AND CONCLUSIONS: Fourteen patients were diagnosed as having DBSTs. The responses to treatment were ten cases of partial response, three of stable disease, and one of progressive disease. General and/or neurological symptoms improved in more than 80% of patients. The median time from diagnosis to progression and to death were, nonetheless, 8 (range of 3-13) and 13 (range of 4-25) months, respectively, with a 2-year overall survival rate of 12.3% [standard error (SE) 11.2]. Seventeen patients were diagnosed as having FBSTs. Gross total removal was achieved in 4/17 cases, subtotal removal in 7/17, and partial removal in 6/17. There was one surgery-related death. Eight out of 17 patients had adjuvant chemo- and/or radiotherapy after progression: 6/8 are without neurological symptoms and 2/8 have died due to tumor progression. The 4-year overall and disease-free survival rates are 87.4 (SE 8.4) and 58.8% (SE 11.9), respectively, the extent of resection being the most important prognostic factor (p=0.012). DBSTs continue to carry a dismal prognosis, thus demanding new treatment modalities; FBSTs can be treated surgically and patients benefit from a better prognosis.

Phase II trial of temozolomide in children with recurrent high-grade glioma.

PURPOSE: The objective of the study was to evaluate the efficacy and toxicity of Temozolomide (TMZ) administered for 5 consecutive days in three daily dosing in children with recurrent or refractory high-grade glioma. PATIENTS AND METHODS: Twenty-four patients with a median age of 10.5 years were enrolled onto this open-label, multicenter, phase II study. The patients were previously treated with surgical resection (17 of 24), radiotherapy (19 of 24) and chemotherapy (18 of 24). Therapy was administered orally three times a day for 5 consecutive days at the dose of 200 mg/m(2)/dx5 for chemotherapy naive patients. In patients heavily pretreated with chemotherapy the starting dose was of 150 mg/m(2)/dx5. RESULTS: A total of 95 cycles were administered. The median progression free-survival (PFS) was 3 months for the entire group while disease stabilization was obtained in 7 patients (29.1%), all with supratentorial tumors. No CR or PR was observed. TMZ treatment showed a limited toxicity. Thrombocytopenia was the most common hematological adverse effect. Our data suggest a marginal activity of TMZ in children with recurrent high-grade glioma.

Thyroid dysfunction as a late effect in childhood medulloblastoma: a comparison of hyperfractionated versus conventionally fractionated craniospinal radiotherapy.

PURPOSE: Primary hypothyroidism is a common sequela of craniospinal radiotherapy in the treatment of childhood medulloblastoma. Due to the strong radiobiologic rationale, hyperfractionation can reduce the delayed effects of radiation injury. METHODS AND MATERIALS: The authors compared the incidence of thyroid dysfunction after conventionally fractionated radiotherapy (Group A, n = 20 patients) vs. hyperfractionated radiotherapy (Group B, n = 12 patients) in a group of pediatric patients with posterior fossa primitive neuroectodermal tumor (PNET). RESULTS: The mean age at the time of tumor diagnosis was 7.4 years in Group A and 8.4 years in Group B. Thyroid function was evaluated yearly, with ultrasonographic examination every 2 years. The patients were followed after diagnosis for a mean of 10.8 years for Group A and 6.0 years for Group B. Approximately 80% of the Group A (16/20) and 33.3% of the Group B (4/12) patients developed primary hypothyroidism within a similar period after irradiation (4.2 vs. 3.5 years, respectively). Analysis by cumulative incidence function demonstrated a significant difference in the risk of developing thyroid dysfunction between these two groups of patients (p < 0.05). Ultrasonography showed reduced thyroid volume in 7 Group A patients and structural changes in 21 patients (17 Group A, 4 Group B cases); a thyroid benign nodule was detected in 2 Group A patients. CONCLUSIONS: The current study findings suggest that the use of hyperfractionated craniospinal radiotherapy in the treatment of childhood medulloblastoma is associated with a lower risk of these patients' developing late thyroid dysfunction.