CUBITAL TUNNEL SYNDROME DUE TO AN INTRANEURAL GANGLION CYST OF THE ULNAR NERVE.

Cubital tunnel syndrome is the second most common neuropathy of the upper extremity. Cubital tunnel syndrome caused by intraneural ganglion cysts is rare in clinical practice. We present the case of a 71-year-old male patient with a 4-month history of cubital tunnel syndrome of the left elbow due to an intraneural ganglion cyst. After revision of the ulnar nerve and resection of the intraneural cyst nearly complete recovery was achieved within a 5 month follow-up but some sensory deficits of the fifth fingertip. We recommend preoperative ultrasound examination of the cubital tunnel even in cases with clear diagnosis. Ganglion cyst as a cause of cubital tunnel is rare but needs to be diagnosed and treated as soon as possible to prevent irreversible complications.

TRAUMATIC PULMONARY HERNIATION: A RARE CHEST TRAUMA MANIFESTATION.

Traumatic pulmonary hernia is an uncommon occurrence resulting from chest trauma, typically covered by the skin. Chest trauma may arise from penetrating or blunt mechanisms, with blunt trauma being more frequently observed. When lung herniation transpires, various symptoms such as chest pain, dyspnea, subcutaneous emphysema, bone crepitation, and hemoptysis (in cases of lung parenchymal damage) may manifest. We present the case of a 66-year-old woman suffering from chest pain and dyspnea after blunt chest trauma due to a fall induced by delirium following alcohol abuse.

AN INTRATENDINOUS GANGLION CYST OF THE PATELLAR TENDON: A RARE CAUSE OF ANTERIOR KNEE PAIN.

Ganglion cysts in the knee region can manifest as anterior knee pain. Unlike synovial cysts, these lesions lack synovial epithelial lining and occur secondary to mucoid degeneration of connective tissue because, often in response to chronic irritation and repetitive traumas. However, an intratendinous location is a rare finding. In the knee region, infrapatellar fat pad, the alar folds, and the anterior cruciate ligament are recognized to degenerate into ganglion. There are few case reports describing an involvement of the patellar tendon. We present the clinical case of a 72 years old male patient suffering from anterior knee pain attributed to an intratendinous ganglion cyst of the patellar tendon, obviously after a single traumatic event. After aspiration of the ganglion cyst the patient reported no complaints, and there has been no recurrence during the latest follow-up examination.

HOW TO AVOID FRACTURE OF THE LOCKING SCREW IN MODULAR REVISION ARTHROPLASTY OF THE HIP USING THE MRP TITAN REVISION SYSTEM.

The use of modular femoral stems in primary and revision arthroplasty of the hip has become popular within the last decade. On the other hand, modularity creates new potential problems like fretting, crevice and galvanic corrosion, component loosening, dissociation, and fracture of modular prostheses. Recently a problem of fracture of a locking screw in revision arthroplasty of the hip using the MRP Titan Stem (Peter Brehm GmbH, Weisendorf, 91085 Germany) appeared. The aim of this study is to evaluate the meaning of surface contamination in respect to fracture mechanism. The titanium nitrid coated locking screw M6 of the MRP Titan system was in vitro tested in several series. After experimental contamination (series 1-4) morse taper junction was fixed by the locking screw with a torque wrench: Series 1: The influence of contamination with dried blood was examined while screw M6 was put into pig's blood. Series 2: The influence of contamination with dried blood and biologic tissue was examined while screw M6 was covered with a pulpous mixture of pig's blood, pig's muscle, and pig's fat tissue. Series 3: The influence of contamination with dried blood and biologic tissue was examined while female thread was covered with a pulpous mixture of pig's blood, pig's muscle, and pig's fat tissue. Series 4: The influence of cleaning of the contaminated female component was examined while female thread contamination (with a pulpous mixture of pig's blood, pig's muscle, and pig's fat tissue) was cleaned with 50 ml saline solution. Comparing series 1 with series 4, series 2 with series 4 and series 3 with series 4 statistical analysis showed a significant reduction of fractures of screw M6 (p-values <0.01). To avoid fracture of the screw M6 of the MRP Titan System we recommend cleaning the inner thread of the morse taper junction with saline solution before junction is fixed with the screw and the torque wrench.

RETURN TO SPORT AFTER SURGICAL TREATED TIBIAL PLATEAU FRACTURES.

Tibial plateau fractures (TPF) comprise 1% of all fractures, despite their limited frequency, due to their intraarticular nature they commonly result in significant functional morbidity. Generally, younger, and middle-aged men (64%) tend to have fractures as a result of high-energy trauma, such as high-speed motor vehicle accidents or falls from a considerable height, while older women have low-energy fractures (35%). While there is growing evidence on the clinical and radiological outcomes of surgical techniques, there remains limited evidence on return to sport following TPF. Aim of this retrospective study is to determine the sporting abilities of patients after operative treatment of TPF. 47 Patients (20 women, 27 men) who underwent surgical treatment for a TPF were surveyed by a questionnaire to determine their sporting activity were followed- up a mean of 47.6 months (Min: 12, Max: 115). All the patients fractures were systematically assessed using AO- Classification. The Lysholm-Gillquist scores, IKDC Score, Injury - Psychological Readiness to Return to Sport (I-PRRS) scales and ACL-Return to Sport Injury Scale (ACL-RSI) were used to assess clinical outcomes. All fractures united, and no revision surgeries were required. There were no intraoperative complications. Mean postoperative IKDC score was 75 (Min:13, Max: 100), mean postoperative Lysholm score was 82 (Min: 5, Max: 100), mean ACL-Return to Sport Injury Scale (ACL-RSI) was 66 (Min: 0, Max: 100), Injury-Psychological Readiness to Return to Sport Scale (I-PRRS-Scale) was 39 (Min: 0, Max: 80). 31/47 patients were able to return to their former -sports- activity level, 8/47 did not achieve their former sports activity level before injury, 2/47 cases changed their kind of sport and 6/47 stopped sporting activities. Tibial plateau fractures -a severe injury- have a great effect on patients in terms of quality and quantity of sporting activity. Nevertheless, most of our surgical treated patients were satisfied with the outcome with good values in the Lysholm- score, I-PRRS- Scale, IKDC score and ACL-Return to Sport Injury Scale.

INCIDENTAL INTRAOSSEOUS CALCANEAL LIPOMA IN A PATIENT SUFFERING FROM PLANTARFASZIITIS.

Intraosseous calcaneal lipoma is a rare benign bone tumor. The incidence of intraosseous lipoma involving the calcaneus has been noted to account for fewer than 8-15% of all intraosseous lipoma. The etiology of the lesion is unknown. A post-traumatic secondary bone reaction, healing bone infarct, and benign neoplasm have been discussed. The symptoms can be nonspecific, varying from dull, intermittent pain to activity-related plantar pain. This pain can predictably be misdiagnosed as plantar fasciitis. We present the case of a 49-year-old male patient suffering from plantar fasciitis for three months and incidental asymptomatic intraosseous calcaneal lipoma, which was diagnosed by x-ray and CT scan. As the patient was out of complaints, the typical CT findings we saw no indication for biopsy but recommended regular CT and MRI controls.;

INTRAMUSCULAR MYXOMA OF THE BUTTOCK- A CASE REPORT.

Intramuscular myxoma (IM) is a benign, soft tissue neoplasm of mesenchymal origin. IM is rare, with an incidence of between 0.1 and 0.13 in every 100,000 individuals. Onset is usually between the fourth and seventh decades of life, predominantly in women (70%). The thigh is the common site of involvement seen in 51% patients, followed by upper arm (9%), calf (7%), and rarely in buttocks. We present the case of a 63-year-old female patient with a 6-month history of a growing IM of the right buttock. Due to rapid tumor growth resection of the tumor was indicated to obtain histopathological examination and to rule out malignancy. Marginal surgical removal was performed. Histopathological examination brought the diagnosis of a big intramuscular myxoma. There is no recurrence at latest follow-up.

[Intense pulsed light (IPL) as a therapeutic option for Meibomian gland dysfunction]. / Pulslichttherapie ("intense pulsed light") als Therapieoption bei der Behandlung der Meibom-Drüsen-Dysfunktion.

Meibomian gland dysfunction (MGD) is a common cause of dry eye disease. Intense pulsed light (IPL) treatment is a new and approved therapeutic option for MGD. The treatment consists of 2-4 sessions where light impulses are applied to the lower lid and temporal lid margin. The IPL technique is a safe form of treatment when the required safety precautions are followed. Current studies document an improvement of patients' subjective symptoms and objectively measured clinical parameters.

Correction: Whole-genome sequencing of chronic lymphocytic leukaemia reveals distinct differences in the mutational landscape between IgHVmut and IgHVunmut subgroups.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Association between DRD2 and DRD3 gene polymorphisms and gastrointestinal symptoms induced by levodopa therapy in Parkinson's disease.

Levodopa is the most used drug to treat motor symptoms in Parkinson's disease (PD). However, dopaminergic side effects such as nausea and vomiting may occur. Several evidences indicate a major role for dopamine receptors D2 (DRD2) and D3 (DRD3) in emetic activity. The aim of this study was to investigate the relationship of DRD2 rs1799732 and DRD3 rs6280 gene polymorphisms with gastrointestinal (GI) symptoms induced by levodopa in PD patients. Two hundred and seventeen PD patients on levodopa therapy were investigated. DRD2 rs1799732 and DRD3 rs6280 polymorphisms were genotyped by PCR-based methods. Multiple Poisson regression method with robust variance estimators was performed to assess the association between polymorphisms and gastrointestinal symptoms. The analyses showed that DRD2 Ins/Ins (prevalence ratio (PR)=2.374, 95% confidence interval (CI): 1.105-5.100; P=0.027) and DRD3 Ser/Ser genotypes (PR=1.677, 95% CI 1.077-2.611; P=0.022) were independent and predictors of gastrointestinal symptoms associated with levodopa therapy. Despite all the efforts to alleviate GI symptoms, this adverse effect still occurs in PD patients. Pharmacogenetic studies of GI symptoms induced by levodopa therapy have the potential to display new ways to better understand the molecular mechanisms involved in these side effects.

Whole-genome sequencing of chronic lymphocytic leukaemia reveals distinct differences in the mutational landscape between IgHVmut and IgHVunmut subgroups.

This corrects the article DOI: 10.1038/leu.2017.177.

Aspergillus galactomannan detection in exhaled breath condensate compared to bronchoalveolar lavage fluid for the diagnosis of invasive aspergillosis in immunocompromised patients.

OBJECTIVES: Exhaled breath condensate (EBC) is a noninvasive means of sampling the airways that has shown significant promise in the diagnosis of many disorders. There have been no reports of its usefulness in the detection of galactomannan (GM), a component of the cell wall of Aspergillus. The suitability of EBC for the detection of GM for the diagnosis of invasive aspergillosis (IA) using the Platelia Aspergillus enzyme-linked immunosorbent assay was investigated. METHODS: Prospective, cross-sectional study of lung transplant recipient and haemotologic malignancy patients at a university centre. EBC samples were compared to concomitant bronchoalveolar lavage (BAL) samples among lung transplant recipients and healthy controls. EBC was collected over 10 minutes using a refrigerated condenser according to the European Respiratory Society/American Thoracic Society recommendations, with the BAL performed immediately thereafter. RESULTS: A total of 476 EBC specimens with 444 matched BAL specimens collected from lung transplant recipients (n = 197) or haemotologic malignancy patients (n = 133) were examined. Both diluted and untreated EBC optical density (OD) values (0.0830, interquartile range (IQR) 0.0680-0.1040; and 0.1130, IQR 0.0940-0.1383), respectively, from all patients regardless of clinical syndrome were significantly higher than OD values in healthy control EBCs (0.0508, IQR 0.0597-0.0652; p < 0.0001). However, the OD index values did not correlate with the diagnosis of IA (44 samples were associated with IA). Furthermore, no significant correlation was found between EBC GM and the matched BAL specimen. CONCLUSIONS: GM is detectable in EBC; however, no correlation between OD index values and IA was noted in lung transplant recipients.

Effect of an antimicrobial stewardship programme on antimicrobial utilisation and costs in patients with leukaemia: a retrospective controlled study.

OBJECTIVES: To examine the effectiveness of an antimicrobial stewardship programme on utilization and cost of antimicrobials in leukaemia patients in Canada. METHODS: We conducted a multisite retrospective observational time series study from 2005 to 2013. We implemented academic detailing as the intervention of an antimicrobial stewardship programme in leukaemia units at a hospital, piloted February-July 2010, then fully implemented December 2010-March 2013, with no intervention in August-November 2010. Internal control was the same hospital's allogeneic haematopoietic stem-cell transplantation unit. External control was the combined leukaemia-haematopoietic stem-cell transplantation unit at another hospital. Primary outcome was antimicrobial utilization (antibiotics and antifungals) in defined daily dose per 100 patient-days (PD). Secondary outcomes were antimicrobial cost (Canadian dollars per PD); cost and utilization by drug class; length of stay; 30-day inpatient mortality; and nosocomial Clostridium difficile infection. We used autoregressive integrated moving average models to evaluate the impact of the intervention on outcomes. RESULTS: The intervention group included 1006 patients before implementation and 335 during full implementation. Correspondingly, internal control had 723 and 264 patients, external control 1395 and 864 patients. Antimicrobial utilization decreased significantly in the intervention group (p <0.01, 278 vs. 247 defined daily dose per 100 PD), increased in external control (p = 0.02, 237.4 vs. 268.9 defined daily dose per 100 PD) and remained stable in internal control (p = 0.66). Antimicrobial cost decreased in the intervention group (p = 0.03; $154.59 per PD vs. $128.93 per PD), increased in external control (p = 0.01; $109.4 per PD vs. $135.97 per PD) but was stable in internal control (p = 0.27). Mortality, length of stay and nosocomial C. difficile rate in intervention group remained stable. CONCLUSIONS: The antimicrobial stewardship programme reduced antimicrobial use in leukaemia patients without affecting inpatient mortality and length of stay.

[Newly occurring loss of visual acuity in choroidal osteoma]. / Neu aufgetretene Visusminderung bei choroidalem Osteom.

PURPOSE: Approach to loss of visual acuity in a patient with a choroidal osteoma (CO) which had been stable for seven years. METHODS: Fluorescence angiography confirmed a choroidal neovascularization (CNV) as the cause of the loss of visual acuity. Treatment with intravitreal (IVT) injection of ranibizumab. RESULTS: Increase of visual acuity and decrease of edema after IVT injection. CONCLUSION: Monitoring is necessary even for primarily benign CO in order to detect secondary complications causing loss of visual acuity, e. g. secondary CNV. Anti-VEGF IVT represents an approved treatment option.

Whole-genome sequencing of chronic lymphocytic leukaemia reveals distinct differences in the mutational landscape between IgHVmut and IgHVunmut subgroups.

Chronic lymphocytic leukaemia (CLL) consists of two biologically and clinically distinct subtypes defined by the abundance of somatic hypermutation (SHM) affecting the Ig variable heavy-chain locus (IgHV). The molecular mechanisms underlying these subtypes are incompletely understood. Here, we present a comprehensive whole-genome sequencing analysis of somatically acquired genetic events from 46 CLL patients, including a systematic comparison of coding and non-coding single-nucleotide variants, copy number variants and structural variants, regions of kataegis and mutation signatures between IgHVmut and IgHVunmut subtypes. We demonstrate that one-quarter of non-coding mutations in regions of kataegis outside the Ig loci are located in genes relevant to CLL. We show that non-coding mutations in ATM may negatively impact on ATM expression and find non-coding and regulatory region mutations in TCL1A, and in IgHVunmut CLL in IKZF3, SAMHD1,PAX5 and BIRC3. Finally, we show that IgHVunmut CLL is dominated by coding mutations in driver genes and an aging signature, whereas IgHVmut CLL has a high incidence of promoter and enhancer mutations caused by aberrant activation-induced cytidine deaminase activity. Taken together, our data support the hypothesis that differences in clinical outcome and biological characteristics between the two subgroups might reflect differences in mutation distribution, incidence and distinct underlying mutagenic mechanisms.

Effects of single moor baths on physiological stress response and psychological state: a pilot study.

Moor mud applications in the form of packs and baths are widely used therapeutically as part of balneotherapy. They are commonly given as therapy for musculoskeletal disorders, with their thermo-physical effects being furthest studied. Moor baths are one of the key therapeutic elements in our recently developed and evaluated 3-week prevention program for subjects with high stress level and increased risk of developing a burnout syndrome. An embedded pilot study add-on to this core project was carried out to assess the relaxing effect of a single moor bath. During the prevention program, 78 participants received a total of seven moor applications, each consisting of a moor bath (42 °C, 20 min, given between 02:30 and 05:20 p.m.) followed by resting period (20 min). Before and after the first moor application in week 1, and the penultimate moor application in week 3, salivary cortisol was collected, blood pressure and heart rate were measured, and mood state (Multidimensional Mood State Questionnaire) was assessed. A Friedman test of differences among repeated measures was conducted. Post hoc analyses were performed using the Wilcoxon signed-rank test. A significant decrease in salivary cortisol concentration was seen between pre- and post-moor bath in week 1 (Z = -3.355, p = 0.0008). A non-significant decrease was seen between pre- and post-moor bath in week 3. Mood state improved significantly after both moor baths. This pilot study has provided initial evidence on the stress-relieving effects of single moor baths, which can be a sensible and recommendable therapeutic element of multimodal stress-reducing prevention programs. The full potential of moor baths still needs to be validated. A randomized controlled trial should be conducted comparing this balneo-therapeutic approach against other types of stress reduction interventions.

Results of the randomized phase IIB ARCTIC trial of low-dose rituximab in previously untreated CLL.

ARCTIC was a multicenter, randomized-controlled, open, phase IIB non-inferiority trial in previously untreated chronic lymphocytic leukemia (CLL). Conventional frontline therapy in fit patients is fludarabine, cyclophosphamide and rituximab (FCR). The trial hypothesized that including mitoxantrone with low-dose rituximab (FCM-miniR) would be non-inferior to FCR. A total of 200 patients were recruited to assess the primary end point of complete remission (CR) rates according to IWCLL criteria. Secondary end points were progression-free survival (PFS), overall survival (OS), overall response rate, minimal residual disease (MRD) negativity, safety and cost-effectiveness. The trial closed following a pre-planned interim analysis. At final analysis, CR rates were 76 FCR vs 55% FCM-miniR (adjusted odds ratio: 0.37; 95% confidence interval: 0.19-0.73). MRD-negativity rates were 54 FCR vs 44% FCM-miniR. More participants experienced serious adverse reactions with FCM-miniR (49%) compared to FCR (41%). There are no significant differences between the treatment groups for PFS and OS. FCM-miniR is not expected to be cost-effective over a lifetime horizon. In summary, FCM-miniR is less well tolerated than FCR with an inferior response and MRD-negativity rate and increased toxicity, and will not be taken forward into a confirmatory trial. The trial demonstrated that oral FCR yields high response rates compared to historical series with intravenous chemotherapy.

EGR2 mutations define a new clinically aggressive subgroup of chronic lymphocytic leukemia.

Recurrent mutations within EGR2 were recently reported in advanced-stage chronic lymphocytic leukemia (CLL) patients and associated with a worse outcome. To study their prognostic impact, 2403 CLL patients were examined for mutations in the EGR2 hotspot region including a screening (n=1283) and two validation cohorts (UK CLL4 trial patients, n=366; CLL Research Consortium (CRC) patients, n=490). Targeted deep-sequencing of 27 known/postulated CLL driver genes was also performed in 38 EGR2-mutated patients to assess concurrent mutations. EGR2 mutations were detected in 91/2403 (3.8%) investigated cases, and associated with younger age at diagnosis, advanced clinical stage, high CD38 expression and unmutated IGHV genes. EGR2-mutated patients frequently carried ATM lesions (42%), TP53 aberrations (18%) and NOTCH1/FBXW7 mutations (16%). EGR2 mutations independently predicted shorter time-to-first-treatment (TTFT) and overall survival (OS) in the screening cohort; they were confirmed associated with reduced TTFT and OS in the CRC cohort and independently predicted short OS from randomization in the UK CLL4 cohort. A particularly dismal outcome was observed among EGR2-mutated patients who also carried TP53 aberrations. In summary, EGR2 mutations were independently associated with an unfavorable prognosis, comparable to CLL patients carrying TP53 aberrations, suggesting that EGR2-mutated patients represent a new patient subgroup with very poor outcome.

Targeted deep sequencing reveals clinically relevant subclonal IgHV rearrangements in chronic lymphocytic leukemia.

The immunoglobulin heavy-chain variable region gene (IgHV) mutational status is considered the gold standard of prognostication in chronic lymphocytic leukemia (CLL) and is currently determined by Sanger sequencing that allows the analysis of the major clone. Using next-generation sequencing (NGS), we sequenced the IgHV gene from two independent cohorts: (A) 270 consecutive patient samples obtained at diagnosis and (B) 227 patients from the UK ARCTIC-AdMIRe clinical trials. Using complementary DNA from purified CD19+CD5+ cells, we demonstrate the presence of multiple rearrangements in independent experiments and showed that 24.4% of CLL patients express multiple productive clonally unrelated IgHV rearrangements. On the basis of IgHV-NGS subclonal profiles, we defined five different categories: patients with (a) multiple hypermutated (M) clones, (b) 1 M clone, (c) a mix of M-unmutated (UM) clones, (d) 1 UM clone and (e) multiple UM clones. In population A, IgHV-NGS classification stratified patients into five different subgroups with median treatment-free survival (TFS) of >280(a), 131(b), 94(c), 29(d), 15(e) months (P<0.0001) and a median OS of >397(a), 292(b), 196(c), 137(d) and 100(e) months (P<0.0001). In population B, the poor prognosis of multiple UM patients was confirmed with a median TFS of 2 months (P=0.0038). In conclusion, IgHV-NGS highlighted one quarter of CLL patients with multiple productive IgHV subclones and improves disease stratification and raises important questions concerning the pre-leukemic cellular origin of CLL.

Venous thromboembolism prevention during asparaginase-based therapy for acute lymphoblastic leukemia.

BACKGROUND: Venous thromboembolism (vte) is a recognized complication in patients treated with asparaginase-containing chemotherapy regimens; the optimal preventive strategy is unclear. We assessed the safety and efficacy of prophylaxis using low-dose low molecular weight heparin in adult patients with acute lymphoblastic leukemia in complete remission treated with an asparaginase-based post-remission chemotherapy regimen. METHODS: As part of the intensification phase of the Dana-Farber Cancer Institute 91-01 regimen, asparaginase was administered weekly to 41 consecutive patients for 21-30 weeks; these patients also received prophylaxis with enoxaparin 40 mg daily (60 mg for patients ≥80 kg). Outcomes were assessed against outcomes in a comparable cohort of 99 patients who received the same chemotherapy regimen without anticoagulation prophylaxis. RESULTS: The overall rate of symptomatic venous thrombosis was not significantly different in the prophylaxis and non-prophylaxis cohorts (18.92% and 21.74% respectively). Among patients receiving prophylaxis, vte occurred in higher proportion in those who weighed at least 80 kg (42.86% vs. 4.35%, p = 0.0070). No major bleeding complications occurred in the prophylaxis group (minor bleeding: 8.1%). CONCLUSIONS: Prophylaxis with low-dose enoxaparin during the intensification phase was safe, but was not associated with a lower overall proportion of vte.