Cranio-cervical junction malformation causing cord compression in infant with achondroplasia: a bigger picture.

INTRODUCTION: Achondroplasia is a genetic disorder known for short stature and skeletal abnormalities. CASE REPORT: We present a case of narrowing of the foramen magnum from a large opisthion extending to the spinal canal. CONCLUSION: Foramen magnum stenosis and cervicomedullary stenosis are potentially life threatening neurological manifestations of achondroplasia.

Developing classification criteria for skin-predominant dermatomyositis: the Delphi process.

BACKGROUND: The European League Against Rheumatism/American College of Rheumatology classification criteria for inflammatory myopathies are able to classify patients with skin-predominant dermatomyositis (DM). However, approximately 25% of patients with skin-predominant DM do not meet two of the three hallmark skin signs and fail to meet the criteria. OBJECTIVES: To develop a set of skin-focused classification criteria that will distinguish cutaneous DM from mimickers and allow a more inclusive definition of skin-predominant disease. METHODS: An extensive literature review was done to generate items for the Delphi process. Items were grouped into categories of distribution, morphology, symptoms, antibodies, histology and contextual factors. Using REDCap™, participants rated these items in terms of appropriateness and distinguishing ability from mimickers. The relevance score ranged from 1 to 100, and the median score determined a rank-ordered list. A prespecified median score cut-off was decided by the steering committee and the participants. There was a pre-Delphi and two rounds of actual Delphi. RESULTS: There were 50 participating dermatologists and rheumatologists from North America, South America, Europe and Asia. After a cut-off score of 70 during the first round, 37 of the initial 54 items were retained and carried over to the next round. The cut-off was raised to 80 during round two and a list of 25 items was generated. CONCLUSIONS: This project is a key step in the development of prospectively validated classification criteria that will create a more inclusive population of patients with DM for clinical research. What's already known about this topic? Proper classification of patients with skin-predominant dermatomyositis (DM) is indispensable in the appropriate conduct of clinical/translational research in the field. The only validated European League Against Rheumatism/American College of Rheumatology criteria for idiopathic inflammatory myopathies are able to classify skin-predominant DM. However, a quarter of amyopathic patients still fail the criteria and does not meet the disease classification. What does this study add? A list of 25 potential criteria divided into categories of distribution, morphology, symptomatology, pathology and contextual factors has been generated after several rounds of consensus exercise among experts in the field of DM. This Delphi project is a prerequisite to the development of a validated classification criteria set for skin-predominant DM.

Literature review and case series of haemorrhagic cholecystitis.

A diagnosis of haemorrhagic cholecystitis is difficult to make as it is rare and mimics other common disorders. We present three patients who presented with haemorrhagic cholecystitis, two of whom were on anti-coagulation at presentation. All 3 patients were treated conservatively, 2 with percutaneous cholecystostomy drainage and 1 patient with intravenous antibiotics. There are few guidelines on the management of such a condition.

Fatigue in systemic lupus erythematosus and other autoimmune skin diseases.

BACKGROUND: Fatigue is a well-established symptom in systemic lupus erythematosus (SLE), but has not been well characterized in other skin-limited autoimmune diseases such as cutaneous lupus erythematosus (CLE), amyopathic dermatomyositis (ADM) or autoimmune blistering diseases (AIBD). OBJECTIVES: In this retrospective study, we compared fatigue in controls (n = 84) with that in patients enrolled in prospective longitudinal databases with SLE (n = 165), CLE (n = 226), ADM (n = 136) and AIBD (n = 79). METHODS: We used the 36-Item Short Form Survey (SF-36) vitality scale to analyse median scores and the percentages of patients with clinically significant fatigue (defined as a score ≤ 35) between experimental groups and controls. RESULTS: Median and interquartile range (IQR) vitality scores demonstrated greater fatigue in the experimental groups (SLE 35, IQR 20-55; CLE 50, IQR 30-70; ADM 50, IQR 30-65; AIBD 55, IQR 35-70) than in controls (73, IQR 65-85) (P < 0·05 for each experimental group vs. control). The SLE group had worse fatigue than all of the other groups (P < 0·05 SLE vs. each group), but there was no difference between the CLE, ADM or AIBD groups (all P > 0·05). In addition, the experimental groups had more clinically significant fatigue (score ≤ 35) (SLE 44·2%, CLE 25·2%, ADM 31·6%, AIBD 24·1%) than controls (2%) (P < 0·01 for each experimental group vs. control). The SLE group had more clinically significant fatigue than the CLE group (P < 0·01); however, there was no difference in clinically significant fatigue between SLE and either ADM (P = 0·17) or AIBD (P = 0·055). CONCLUSIONS: These findings demonstrate that patients with skin-limited autoimmune disease experience more fatigue than controls. Fatigue is an important symptom that negatively affects quality of life for patients. It should be addressed by clinicians and measured in future clinical trials.

Evaluation of the reliability and validity of the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) in paediatric cutaneous lupus among paediatric dermatologists and rheumatologists.

BACKGROUND: The Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) is a reliable outcome measure for cutaneous lupus erythematosus (CLE) in adults used in clinical trials. However, it has not been validated in children, limiting clinical trials for paediatric CLE. OBJECTIVES: This study aimed to validate the CLASI in paediatrics. METHODS: Eleven paediatric patients with CLE, six dermatologists and six rheumatologists participated. The physicians were trained to use the CLASI and Physician's Global Assessment (PGA), and individually rated all patients using both tools. Each physician reassessed two randomly selected patients. Within each physician group, the intraclass correlation coefficient (ICC) was calculated to assess the reliability of each measure. RESULTS: CLASI activity scores demonstrated excellent inter- and intrarater reliability (ICC > 0·90), while the PGA activity scores had good inter-rater reliability (ICC 0·73-0·77) among both specialties. PGA activity scores showed excellent (ICC 0·89) and good intrarater reliability (ICC 0·76) for dermatologists and rheumatologists, respectively. Limitations of this study include the small sample size of patients and potential recall bias during the physician rerating session. CONCLUSIONS: CLASI activity measurement showed excellent inter- and intrarater reliability in paediatric CLE and superiority over the PGA. These results demonstrate that the CLASI is a reliable and valid outcome instrument for paediatric CLE.

The diagnosis and classification of amyopathic dermatomyositis: a historical review and assessment of existing criteria.

BACKGROUND: Diagnostic criteria are used to identify a patient having a disease in a clinical setting, whereas classification criteria create a well-defined population for research purposes. The diagnosis and classification of amyopathic dermatomyositis (ADM) have not been recognized by most existing criteria for idiopathic inflammatory myopathies (IIMs). To address this, several criteria were proposed to define ADM either as a distinct disease entity or as a subset of the spectrum of IIMs. OBJECTIVES: To discuss the diagnosis and classification of ADM and to assesses the available criteria in identifying cases of ADM and/or distinguishing it from dermatological mimickers such as lupus erythematosus. METHODS: We conducted an extensive literature search using the PubMed database from June 2016 to August 2018, using the search terms 'amyopathic dermatomyositis', 'diagnosis' and 'classification'. RESULTS: The European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) criteria, which are the only validated classification criteria for adult and juvenile IIM and their major subgroups, include three cutaneous items (Göttron sign, Göttron papules, heliotrope rash) to be able to classify ADM. This international and multispecialty effort is a huge step forward in the classification of skin-predominant disease in dermatomyositis. However, about 25% of the population with ADM do not meet two out of the three skin features and are misdiagnosed or classified as having a different disease entity, most commonly lupus erythematosus. CONCLUSIONS: These gaps rationalize the continuous assessment and improvement of existing criteria and/or the development of validated, separate and skin-focused criteria for DM.

Myofibroblastic infiltration of the bowel: A case report and literature review.

INTRODUCTION: Inflammatory myofibroblastic tumours (IMTs), are uncommon tumours which can act with malignant potential. The management of these tumours can be extremely problematic but are often referred to surgical multi-disciplinary team meetings with the intention of surgical and oncological management (Chaudhary [1]). CASE REPORT: A 69-year-old gentleman was admitted with a 2-day history of abdominal pain and vomiting, and a 4-day history of absolute constipation. CT Abdomen Pelvis demonstrated distended loops of small bowel with pronounced fluid levels but no transition point. Intra-operative findings showed a right ileocolic mass adherent to the pelvic side wall and omental caking. Biopsies showed a florid myofibroblastic reaction, not a malignant process. CONCLUSION: IMTS are aggressive lesions but metastases is rare. Abdominal IMTS are difficult to diagnose and manage as they are often initially mistaken for lymphoma or peritoneal metastases. The therapy of choice is surgical resection of the tumour (Firat et al. [3]).

If I had a hammer.

We present the case of a 64-year-old man who was referred to our service after sustaining a self-inflicted nail-gun injury to his chest. He received three nails penetrated into his chest. Computer tomography revealed no massive haemorrhage or damage to major vessels. He underwent an emergency sternotomy, two nails caused pericardial perforation and myocardial injury were noted easily and removed easily via sternotomy. Myocardial injury showed a trajectory near the junction of the left anterior descending artery and the diagonal artery with no significant bleeding appreciated. The third nail was deep in the lung parenchyma at the hilum. A pacemaker magnet was used to locate the third nail, which was subsequently removed. Our case demonstrates the use of magnets in emergency surgery, to locate and remove metallic foreign bodies.

Anomalous right upper lobe venous drainage.

Lung resections are usually not associated with significant bleeding, but can be fatal, especially in cases of video-assisted thoracoscopic surgery (VATS). Anomalous vascular structures could be a major reason for unexpected bleeding in such surgeries. We present a case of an aberrant upper lobe pulmonary vein that was encountered posterior to the right upper lobe bronchus during a right upper lobectomy via thoracotomy. The anomalous pulmonary vein was identified preoperatively on a computed tomography (CT) scan and hence was looked for before dividing the bronchus. Many centres are adopting the VATS approach for performing lung resections. If an anomalous vein is present posterior to the bronchus, it might be in a blind spot and could be damaged inadvertently, leading to profuse and potentially fatal bleeding. We conclude that the identification of anomalous vascular structures prior to surgery with the help of CT helps in avoiding adverse outcomes.

Multiple Looser zones of osteomalacia in Byler disease with associated vitamin D deficiency, phosphaturia, and elevated FGF23.

INTRODUCTION: Byler disease (progressive familial intrahepatic cholestasis) is associated metabolic bone disease as a consequence of chronic malabsorption. CASE PRESENTATION: A 33-year-old man with decompensated liver disease secondary to Byler disease was referred to the orthopaedic department with progressive pain over this right proximal tibia. On examination, he had an antalgic gait. Tenderness was localised to the proximal tibia just distal to the tibial tubercle and bilateral foot swelling. Radiographs showed multiple stress fractures characteristic of Looser zones at various stages of healing in both tibia, metatarsals (third, fourth, and fifth on the right side, and second and fourth on the left) and left femur. Bone mineral density was extremely low. Subsequent investigations were consistent with severe osteomalacia due to a combination of vitamin D deficiency and phosphaturia with elevated fibroblast factor 23 (FGF23). A good clinical response was achieved following supplementation with calcium 1000mg and vitamin D 20µg daily. DISCUSSION: Stress fractures are often associated with delay in diagnosis. Our patient presented to the orthopaedic service with multiple Looser zones that had not been previously detected. As expected, there was biochemical evidence of vitamin D deficiency. An unexpected finding was phosphaturia that was associated with marked elevation in FGF23, which has never been reported previously. CONCLUSION: Byler disease may result in Looser zones of osteomalacia due to chronic malabsorption. Renal phosphorus wasting as a consequence of unexplained marked elevation in FGF23 is thought to have contributed to the onset of osteomalacia.

A case of lung volume reduction surgery with decortication for a septic patient in respiratory failure.

INTRODUCTION: Decortication and lung volume reduction surgery are both major operations and each has its independent risk of morbidity and mortality. CASE REPORT: We present the case of a 41 year old gentleman with left sided empyema and giant bullae of the upper lobe with an active air leak that was transferred to our tertiary referral centre for further management. We performed emergency left thoracotomy, decorticated the left lower lobe with extensive lung volume reduction surgery of the upper lobe. Patient's respiratory status significantly improved along with excellent radiological results. CONCLUSION: Our case demonstrates that a combination of complex procedures is feasible with excellent outcomes.

Short Communication: Elucidation of bacterial community structure on thin-spined porcupine (Chaetomys subspinosus) spines by denaturing.

Thin-spined porcupines (Chaetomys subspinosus) are threatened with extinction and are categorized as vulnerable. This is because of alteration to and loss of their habitat and possible hunting activities in their distribution area. Their spines constitute one of their defense mechanisms, which can be fomites for pathogens to humans. However, little is known about such pathogens. The present study aimed to detect bacteria on spines of C. subspinosus, from the Una Biological Reserve, South of Bahia, northeastern Brazil, by analyzing metagenomic DNA, isolating bacterial culture, using the denaturing gradient gel electrophoresis (DGGE) technique, and sequencing. Six anatomical points were selected for withdrawing spine samples from an individual C. subspinosus. At all sample points, bacteria were detected by bacteriological culture and/or DGGE and sequencing of excised bands. When all samples were combined, standard PCR-DGGE analysis of bacteria present in the spines identified 15 distinct bands, thereby revealing a distinct bacterial community. The main pathogens identified through sequencing were Bacillus cereus, B. thuringiensis, B. anthracis, and B. pumilus. The present study demonstrated the isolation and identification of non-pathogenic and pathogenic bacteria on the spines of C. subspinosus.

Frequency of occupational health concerns in general clinics.

Studies have suggested that occupational disease and injury are under-recognized by clinicians. To estimate the frequency of occupational factors in disease and injury, 108 patients in a general (not occupational) health care facility were interviewed about the frequency and types of workplace-health interactions. Thirty-nine percent reported possible causation by work, and 66% reported a possible increase in symptoms by work, even if not caused by work. Twenty-seven percent reported changing jobs and/or tasks because of work-health interactions. The majority of men and women reported that worksite changes could improve their functional ability at work. This study therefore indicates that (1) occupational health concerns are common in primary care clinics, even if not addressed by clinicians; (2) the definition of occupational health concerns should be broadened to include disease caused by work, disease symptoms worsened by work, and the need for occupational accommodation even if the disease itself is not caused by work; and (3) inquiring about patient concerns about workplace-health interactions can provide clinicians with significant opportunities for primary, secondary, and tertiary prevention.

Potent and selective bicyclic lactam inhibitors of thrombin. Part 4: transition state inhibitors.

Bicyclic piperazinone based thrombin inhibitors of general structure 2 were prepared and evaluated in vitro and in vivo. These inhibitors, having in common an electrophilic basic trans-cyclohexylamine P1 residue, displayed high thrombin affinity, high selectivity against trypsin and good in vivo efficacy in the rat arterial thrombosis model.

Anodic destruction of 4-chlorophenol solution.

The electrochemical oxidation of 4-chlorophenol solutions was studied using a dimensional stable anode (DSA), made of pure titanium sheet mesh coated with Ti/TiO(2) and RuO(2) film. An electrochemical cell with one working electrode and two counter-electrodes was designed. A gas collecting system to collect the electrolysis gaseous products was also designed. The influence of current density (6.51-21.58 mA/cm(2)), pH (2.0-12.6) and initial 4-chlorophenol concentration (25-100 mg/l) on the destruction was investigated. Complete elimination was successfully achieved within 2 h for most investigated conditions. Highest rates of elimination were achieved at a pH of 12.6.A new approach to calculate the current efficiency (CE) of the cell was proposed. The volumes of the gases produced at the anode and at the cathode were the basis for the new CE calculations. It was observed that the worst CE was approximately 20% and the best CE was approximately 89%. The most efficient pH was at 12.6 and the most efficient current density was at 11.39 mA/cm(2).

A putative HCO3- transporter in the cyanobacterium Synechococcus sp. strain PCC 7942.

Cyanobacteria possess an inducible mechanism which enables them to concentrate inorganic carbon (Ci) within the cells. An inactivation library was used to raise the high-CO2-requiring mutant of Synechococcus PCC 7942, IL-2, impaired in HCO3- transport. Analysis of the relevant genomic DNA detected several modifications, probably due to the single crossover recombination, leading to inactivation of ORF467 (designated ictB) in IL-2. IctB contains 10 trans-membrane regions and is homologous to several transport-related proteins from various organisms. Kinetic analyses of HCO3- uptake in the wild type and IL-2 suggested the presence of two or three HCO3- carriers exhibiting different affinities to HCO3-.

A mutant of Synechococcus PCC 7942 impaired in HCO3- uptake.

An inactivation library was used to isolate high-CO2-requiring mutants of Synechococcus PCC 7942. One of them, mutant IL-7, is composed of elongated cells, some 5-15 times longer than the wild-type. IL-7 is impaired in the ability to accumulate inorganic carbon within the cells due to a lesion in HCO3- transport. Consequently, the apparent photosynthetic affinity for external inorganic carbon was about 50-100-fold lower than in the wild-type. Analysis of the genomic region modified in IL-7 demonstrated that the inactivating fragment was composed of two genomically unrelated fragments which were ligated together during the formation of the inactivation library. One of the fragments originated from a known genomic region, rbcLS, encoding ribulose 1,5-bisphosphate carboxylase/oxygenase and the other showed high homology to mutS encoding a DNA mismatch repair protein. We suggest that the primary lesion in IL-7 was in mutS and not in rbcLS, and that the phenotype of IL-7 resulted from secondary random mutations. We were unable to identify the spontaneous mutation(s) due to low transformability of IL-7. Our finding that two unrelated fragments ligated together points to possible mistakes in the identification of the function of putative genes with the aid of an inactivation library.

Modification of topA in Synechococcus sp. PCC 7942 resulted in mutants capable of growing under low but not high concentration of CO2.

Insertion of a cartridge encoding kanamycin resistance within an open reading frame, ORF839, in the cyanobacterium Synechococcus sp. PCC 7942 resulted in merodiploids bearing both the normal and the modified ORF839, suggesting that its gene product is essential for growth. In the absence of kanamycin the mutants were able to grow like the wild type, but in its presence the mutants grew under 0.015% CO2 in air but not under 5% CO2 in air. ORF839, identified in this study, is highly homologous to topA encoding topoisomerase I in several organisms, but it does not contain the zinc-binding motif identified in the C-terminal region of the enzyme from Escherichia coli.