Sanjad-Sakati Syndrome in a 35-day-old Iraqi Infant: A Case Report.

Sanjad-Sakati syndrome is a rare autosomal recessive genetic disorder that presents solely in Arabian people. Our case was reported from the Fallujah Teaching Hospital for Women and Children in Fallujah, Iraq. This syndrome is associated with hypoparathyroidism, growth retardation, atypical facial appearance, and a variable degree of mental retardation. It is usually caused by genetic mutations of the tubulin-folding cofactor E (TBCE; 604934), which is located on the 1q42.3 chromosome. This case was confirmed by a genetic study which revealed a pathogenic variant in the homozygous state in the TBCE gene. Typically, the physical features of this case involve microcephaly, long and narrow face, beaked nose, deep-set eyes, large ears, thin lips, long philtrum, micrognathia, and small hands and feet. Although Sanjad-Sakati syndrome is an incurable disease, early diagnosis helps with appropriate palliative treatment of the patient, reducing other associated metabolic and electrolyte disturbances, and allows for a genetic study and counseling of the family, especially in our society due to the high rate of consanguinity.

Association of OLR1 gene polymorphism with live body weight and body morphometric traits in Awassi ewes: short communication.

BACKGROUND: Oxidized low-density lipoprotein receptor 1 (OLR1) is an endothelial receptor that binds and degrades oxidized low-density lipoproteins (Ox-LDL), thus having a physiological role in metabolism. Polymorphisms in the OLR1 gene are associated with animals with different production traits. Due to this, the study aimed to determine if OLR1 polymorphisms in Awassi ewes associate with live body weight and body measurement. METHODS AND RESULTS: In this study, 200 ewes between the ages of 2.5 and 5 years, not pregnant or lactating, were selected. Phenotypic measurements including live body weight and body measurements were collected. A sheep's blood was collected to extract genomic DNA, genotyped, and sequenced to confirm the presence of the variants that arose from the amplified fragments. One novel C246A single nucleotide polymorphism (SNP) was identified in the OLR1 gene (exon 3) that assigned two genotypes CC and CA. The study indicated significant differences (P ≤ 0.05) in live body weight and body measurements of the genotype CC compared with the genotype CA. The genotype CC correlated positively with live body weight, height at shoulder, height at hip, chest girth, and chest width (r = 0.67, P = 0.02), (r = 0.54, P = 0.03), (r = 0.61, P = 0.02), (r = 0.53, P = 0.01) and (r = 0.66, P = 0.04) respectively. CONCLUSIONS: Sheep with the CC genotype had a higher live body weight and larger body measurement, making them better for productivity. These genotypic data and associations can be used to better select sheep for future marker-assisted selection programs.

Evaluation of smile characteristics of skeletal Class III compared to skeletal Class I female adults.

OBJECTIVE: Esthetic enhancement plays an important role in orthodontic treatment. This study was conducted on females as most girls have their growth spurt at a younger age than boys do, so their demand to facial esthetics, especially those who have residual growth of mandible producing class III effect, requires full understanding to smile features helping in diagnosis and treatment planning for maximum patient satisfaction. MATERIALS AND METHODS: This study was conducted on 30 skeletal Class III and Class I female adults (18-30 years old) who were divided equally into two groups comprising 15 each. Two frontal digital photographs were taken for each subject, one at rest and the other in the posed smile position. Photographs were taken for each subject in the natural head position by a Canon EOS 1200 D camera set on a tripod at a distance of 1.5 m. The incisogingival height of the right maxillary central incisor was clinically measured using a vernier caliper to the nearest 0.1 mm. Photographs were uploaded on Photoshop software for standardization and then uploaded on the Digital Smile Design software (DSD) where the actual incisogingival height of the central incisor was used for automatic calibration. Esthetic components at rest and on smiling were measured for both groups; all linear variables were measured to the nearest 0.1 mm. RESULTS: Class III females tended to have wider smile widths, less gingival display, longer chin heights, shorter lower vertical dimensions, and a higher percentage of nonconsonant and flat smile arcs than Class I subjects. CONCLUSIONS: The components of the smile should be considered as a guide to help in planning and designing the mechanics during comprehensive orthodontic treatment.

Fatal myocarditis and rhabdomyositis in a patient with stage IV melanoma treated with combined ipilimumab and nivolumab.

Combination immune checkpoint blockade with concurrent administration of the anti-ctla4 antibody ipilimumab and the anti-PD-1 antibody nivolumab has demonstrated impressive responses in patients with advanced melanoma and other diseases. That combination has also been associated with increased toxicity, including rare immune-related adverse events. Here we describe a case of fatal steroid-refractory myocarditis and panmyositis associated with the use of this combination in a patient with metastatic melanoma. Correlative studies indicated increased levels of serum interleukin 6 in this patient at the onset of toxicity, suggesting a possible role for anti-interleukin 6 receptor antibodies in the treatment of subsequent cases of this rare, but fatal, toxicity.

Survivorship and long-term outcome of a consecutive series of 200 Scandinavian Total Ankle Replacement (STAR) implants.

AIMS: We report the long-term clinical and radiological outcomes of a consecutive series of 200 total ankle arthroplasties (TAAs, 184 patients) at a single centre using the Scandinavian Total Ankle Replacement (STAR) implants. PATIENTS AND METHODS: Between November 1993 and February 2000, 200 consecutive STAR prostheses were implanted in 184 patients by a single surgeon. Demographic and clinical data were collected prospectively and the last available status was recorded for further survival analysis. All surviving patients underwent regular clinical and radiological review. Pain and function were assessed using the American Orthopaedic Foot and Ankle Society (AOFAS) hindfoot scoring system. The principal endpoint of the study was failure of the implant requiring revision of one or all of the components. Kaplan-Meier survival curves were generated with 95% confidence intervals and the rate of failure calculated for each year. RESULTS: A total of 84 patients (87 ankles) were alive by the end of this study. Of the surviving 84 patients (87 ankles; rheumatoid arthritis (RA), n = 40; OA, n = 47), 45 were women and 39 were men, with a mean age of 54 years (18 to 72 years) at the time of surgery. A total of 32 implants failed (16%), requiring revision surgery. The mean time to revision was 80 months (2 to 257). The implant survival at 15.8 years, using revision as an endpoint, was 76.16% (95% confidence interval (CI) 64.41 to 87.91). We found a steady but low decrease in survival over the study period. The mean AOFAS score improved from 28 (10 to 52) preoperatively to 61 (20 to 90) at long-term follow-up. CONCLUSION: STAR prostheses in the United Kingdom have now been largely superseded by newer design TAAs, potentially with improved characteristics and surgical techniques. The long-term survivorship for the STAR prosthesis can provide a benchmark for these later designs of ankle arthroplasty.

Total ankle arthroplasty: what are the risks?: a guide to surgical consent and a review of the literature.

AIMS: Total ankle arthroplasty (TAA) surgery is complex and attracts a wide variety of complications. The literature lacks consistency in reporting adverse events and complications. The aim of this article is to provide a comprehensive analysis of each of these complications from a literature review, and to compare them with rates from our Unit, to aid clinicians with the process of informed consent. PATIENTS AND METHODS: A total of 278 consecutive total ankle arthroplasties (251 patients), performed by four surgeons over a six-year period in Wrightington Hospital (Wigan, United Kingdom) were prospectively reviewed. There were 143 men and 108 women with a mean age of 64 years (41 to 86). The data were recorded on each follow-up visit. Any complications either during initial hospital stay or subsequently reported on follow-ups were recorded, investigated, monitored, and treated as warranted. Literature search included the studies reporting the outcomes and complications of TAA implants. RESULTS: There were wound-healing problems in nine ankles (3.2%), superficial infection in 20 ankles (7.2%), and deep infection in six ankles (2.2%). Intraoperative fractures occurred in medial malleoli in 27 ankles (9.7%) and in lateral malleoli in four ankles (1.4%). Aseptic loosening and osteolysis were seen 16 ankles (5.8%). Fracture of the polyethylene component occurred in one ankle (0.4%) and edge-loading in seven ankles (2.5%). We observed medial gutter pain in 31 ankles (11.1%). The incidence of thromboembolism occurred in two ankles (0.7%). The results were found to be comparable to the previously reported complications of total ankle arthroplasty in the literature. CONCLUSION: Total ankle arthroplasty continues to evolve and improve the ankle function. Despite high overall complication rates with TAA surgery, most complications appear to be minor and do not affect final clinical outcome. Our results and literature review will help in the consent process and provide detailed complication rates for an informed consent. Cite this article: Bone Joint J 2018;100-B:1352-8.

Amplification of the Atlantic Multidecadal Oscillation associated with the onset of the industrial-era warming.

North Atlantic sea surface temperatures experience variability with a periodicity of 60-80 years that is known as the Atlantic Multidecadal Oscillation (AMO). It has a profound imprint on the global climate system that results in a number of high value societal impacts. However the industrial period, i.e. the middle of the 19th century onwards, contains only two full cycles of the AMO making it difficult to fully characterize this oscillation and its impact on the climate system. As a result, there is a clear need to identify paleoclimate records extending into the pre-industrial period that contain an expression of the AMO. This is especially true for extratropical marine paleoclimate proxies where such expressions are currently unavailable. Here we present an annually resolved coralline algal time series from the northwest Atlantic Ocean that exhibits multidecadal variability extending back six centuries. The time series contains a statistically significant trend towards higher values, i.e. warmer conditions, beginning in the 19th century that coincided with an increase in the time series' multidecadal power. We argue that these changes are associated with a regional climate reorganization involving an amplification of the AMO that coincided with onset of the industrial-era warming.

Tertiary syphilis in the cervical spine: a case report and review of the literature.

As the prevalence of syphilis rises, an increase in tertiary syphilis with spinal involvement is predicted. We report what we believe to be the first case of compressive cervical spine syphilitic gummata, with central cord compression signs. We also review the relevant literature to date. The diagnosis of syphilis in the spine relies on the physician to be aware of it as part of the differential diagnosis. Treponemal laboratory tests are an important aid in establishing a diagnosis.

Accuracy of prognostic scores in decision making and predicting outcomes in metastatic spine disease.

INTRODUCTION: Management of metastatic spinal disease has changed significantly over the last few years. Different prognostic scores are used in clinical practice for predicting survival. The aim of this study was to assess the accuracy of prognostic scores and the role of delayed presentation in predicting the outcome in patients with metastatic spine disease. METHODS: Retrospectively, four years of data were collected (2007-2010). Medical records review included type of tumour, duration of symptoms, expected survival and functional status. The Karnofsky performance score was used for functional assessment. Modified Tokuhashi and Tomita scores were used for survival prediction. RESULTS: A total of 55 patients who underwent surgical stabilisation were reviewed. The mean age was 63 years (range: 32-87 years). The main primary sources of tumours included myeloma, breast cancer, lymphoma, lung cancer, renal cell cancer and prostate cancer. Of the cases studied, 29 patients had posterior instrumented stabilisation alone, 10 patients had an anterior procedure alone and 16 patients (with an expected survival of more than one year) had both anterior and posterior procedures performed. Twenty-three patients presented with spinal cord compression. The mean follow-up duration was 9 months (range: 1-39 months). Patients who were treated within one week of referral survived longer than anticipated. Patients were divided into three groups based on their expected survival. Actual survival was better in all three groups after surgery. Discrepancies in scores were prominent in patients with myeloma, breast and prostate cancers. Functional outcome was better in patients under 65 years of age. CONCLUSIONS: The prognostic scoring systems are not uniformly effective in all types of primary tumours. However, they are useful in decision making for surgical intervention, taking other factors into account, in particular the age of the patient, the type and stage of the primary tumour and general health.

A regression model to predict warfarin dose from clinical variables and polymorphisms in CYP2C9, CYP4F2, and VKORC1: Derivation in a sample with predominantly a history of venous thromboembolism.

BACKGROUND: Pharmacogenomic warfarin dosing has been suggested to produce more accurate dosing and an improved patient safety profile; however, very few models have been derived in patients with venous thromboembolism. We sought to develop a new algorithm to predict maintenance dose in a cohort of patients, using clinical variables and genetic polymorphism in CYP2C9, VKORC1, and CYP4F2. METHODS: Patients on a stable maintenance dose of warfarin, with observed dose ranging from 0.6 to 12mg were recruited from a specialized anticoagulation clinic (Ottawa Hospital Thrombosis Clinic) with genotyping and standardized patient interviews being conducted to collect clinical and genomic variables known to impact warfarin dose. Multivariate linear regression was used to develop the model using a stepwise backwards elimination approach. RESULTS: From 249 enrolled patients with a mean clinical maintenance dose of 5.58mg/day, a model with an R(2) of 58% was developed as: Dose=1.85-0.048(Age)+0.041(BMI)+0.05(Height in cm) - 0.73(Less Exercise) - 1.13(2C9*2 Hetero) - 2.09(2C9*2 Homo) - 1.51(2C9*3 Hetero) -1.43(VKORC1 GA) - 2.86(VKORC1 AA) - 1.33(4F2 CC) -1.24(4F2 CT) - 1.46(Angiotensin II Receptor Antagonist) - 0.84(beta-Blockers). Analysis of residual plots revealed that prediction errors were a function of observed maintenance dose with the model tending to predict higher doses than observed in those with low dose requirements and lower doses than observed in those with higher dose requirement. CONCLUSION: Our study confirms the importance of the CYP4F2 polymorphism. Our model may prove useful in clinical practice but further validation studies are required before implementation into clinical practice.

Prediction of the warfarin maintenance dose after completion of the 10 mg initiation nomogram: do we really need genotyping?

INTRODUCTION: Initiation of warfarin therapy is complicated by its narrow therapeutic index and inter-patient dose-effect variability. A '10-mg nomogram' warfarin initiation protocol permits safe therapeutic anticoagulation in outpatients started on warfarin. We aimed to develop a safe and effective warfarin maintenance dose prediction tool in these patients. METHODS: Baseline potential predictor variables were collected on a retrospective cohort of outpatients initiated on warfarin for venous thromboembolism treatment. The primary outcome was the warfarin maintenance dose, defined as mean warfarin dose over the last 10 days of the first month of warfarin treatment. Univariate and multivariate analyses were performed to determine which baseline variables were warfarin maintenance dose predictors. An independent cohort of patients validated the derived warfarin maintenance dose prediction rule. RESULTS: Patient's age and weight, cumulative dose of warfarin over the first week of induction and international normalized ratio (INR) on days 3, 5 and 8 were statistically significant predictors of the warfarin maintenance dose. Our final prediction rule reads: maintenance dose (in mg) = 2.5 + 10% of the first week cumulative dose - INR value at day 8 + 1.5 if INR was below 2.0 at day 5. In the validation cohort, the predicted dose was strongly correlated with the actual maintenance dose (r = 0.88, P < 0.0001). The mean difference between observed and predicted dose was not clinically significant: -0.1 +/- 1.1 mg. CONCLUSION: In outpatients initiated on warfarin using a '10-mg nomogram', a simple prediction rule can accurately predict warfarin maintenance dose. Prospective studies employing the rule are indicated.

Homozygous mutations in LPIN2 are responsible for the syndrome of chronic recurrent multifocal osteomyelitis and congenital dyserythropoietic anaemia (Majeed syndrome).

BACKGROUND: Majeed syndrome is an autosomal recessive, autoinflammatory disorder characterised by chronic recurrent multifocal osteomyelitis and congenital dyserythropoietic anaemia. The objectives of this study were to map, identify, and characterise the Majeed syndrome causal gene and to speculate on its function and role in skin and bone inflammation. METHODS: Six individuals with Majeed syndrome from two unrelated families were identified for this study. Homozygosity mapping and parametric linkage analysis were employed for the localisation of the gene responsible for Majeed syndrome. Direct sequencing was utilised for the identification of mutations within the genes contained in the region of linkage. Expression studies and in silico characterisation of the identified causal gene and its protein were carried out. RESULTS: The phenotype of Majeed syndrome includes inflammation of the bone and skin, recurrent fevers, and dyserythropoietic anaemia. The clinical picture of the six affected individuals is briefly reviewed. The gene was mapped to a 5.5 cM interval (1.8 Mb) on chromosome 18p. Examination of genes in this interval led to the identification of homozygous mutations in LPIN2 in affected individuals from the two families. LPIN2 was found to be expressed in almost all tissues. The function of LPIN2 and its role in inflammation remains unknown. CONCLUSIONS: We conclude that homozygous mutations in LPIN2 result in Majeed syndrome. Understanding the aberrant immune response in this condition will shed light on the aetiology of other inflammatory disorders of multifactorial aetiology including isolated chronic recurrent multifocal osteomyelitis, Sweet syndrome, and psoriasis.

The syndrome of chronic recurrent multifocal osteomyelitis and congenital dyserythropoietic anaemia. Report of a new family and a review.

UNLABELLED: A new autosomal recessive syndrome of chronic recurrent multifocal osteomyelitis (CRMO) and congenital dyserythropoietic anaemia (CDA) with microcytosis has recently been described in four children (two sibships) of one consangineous Arab family. In this report, we describe the clinical features and course of the syndrome of CRMO and CDA in two additional patients (one sibship) from another consanguineous Arab family and review the literature. The two patients (brother and sister), the products of a consanguineous marriage, developed the syndrome at an early age of 3 weeks and 2 months respectively. The diagnosis of CRMO was confirmed by radiological and technetium isotope bone scans. Bone marrow studies confirmed the diagnosis of CDA. Peripheral blood films showed hypochromia and microcytosis. The sites involved by CRMO were periarticular, mainly around the elbow, knee, wrist and small joints of the hand. The brother is now 21 years old and the sister 3.5 years old and CRMO is still active with frequent relapses. The brother developed flexion deformities at the age of 13 years. Both patients failed to thrive; weight and height were below the 5th percentile. CONCLUSION: This is the second report of the syndrome of chronic recurrent multifocal osteomyelitis and microcytic congenital dyserythropoietic anaemia, confirming it as a clinical entity, inherited as an autosomal recessive trait. The disease is characterised by an early onset, long clinical course of remissions and relapses, and seems to be different from the sporadic form of chronic recurrent multifocal osteomyelitis.

The clinical patterns of myalgia in children with familial Mediterranean fever.

OBJECTIVES: To study the frequency and clinical patterns of myalgia in a defined group of children with familial Mediterranean fever (FMF). METHODS: A prospective 4-year (September 1995-September 1999) study of children with FMF seen in the pediatric FMF clinic of Jordan University teaching hospital. Diagnosis of FMF was made according to published criteria. Once the diagnosis of FMF and myalgia was made, details about myalgia were collected by interview with the child and his/her parents and entered into a special study form. RESULTS: Of 264 children with FMF seen over the study period, 65 (25%) developed myalgia. Three clinical patterns of myalgia were identified: the spontaneous pattern, the exercise-induced pattern, and the protracted febrile myalgia syndrome (PFMS), seen in 8%, 81%, and 11% of patients, respectively. The three patterns differed in the severity of pain, height of fever, and duration of the episode. In 33 children with the exercise-induced myalgia, in which response to colchicine could be reliably assessed, a favorable response was achieved in 97%. Three children with the PFMS had a dramatic response to corticosteroids. CONCLUSIONS: Myalgia in children with FMF is common and can follow three different clinical patterns.

Differential diagnosis of fever of unknown origin in children.

Fever of unknown origin in children follows two main clinical patterns, namely fever of unknown origin and chronic episodic fever of unknown origin. Fever of unknown origin is characterized by daily fever persisting for more than 3 weeks. The main causes are infectious, rheumatologic disorders, and malignancy. Chronic episodic fever of unknown origin is characterized by fever lasting for a few days to a few weeks, followed by a fever-free interval and a sense of well-being. The main causes are familial Mediterranean fever, the hyper-immunoglobulin D syndrome, familial Hibernian fever, Behcet disease, the syndrome of periodic fever, aphthous stomatitis, pharyngitis and adenitis, and cyclic neutropenia.

Poststreptococcal reactive arthritis.

The occurrence of an entity designated poststreptococcal reactive arthritis (PSReA) has been highlighted in recent reports. The syndrome was considered part of the spectrum of acute rheumatic fever by some, whereas others stressed the differences between the two diseases. As distinct from acute rheumatic fever, PSReA is characterized by a shorter latency period between the inciting streptococcal infection and the onset of arthritis, a higher frequency of involvement of the small joints and axial skeleton, poor response to aspirin and other nonsteroidal anti-inflammatory drugs, a protracted course of arthritis, a low incidence of carditis, and absence of other major manifestations of acute rheumatic fever. Recent studies have demonstrated an increased frequency of DRB1*01 in patients with PSReA, which contrasts with the increased frequency of DRB1*16 in rheumatic fever. Because 6% of patients with PSReA have been reported to have late onset carditis, it is judicious to recommend that patients with PSReA receive prophylactic antimicrobials for a minimum period of 5 years or until the age of 21 years, whichever is longer.