Linaclotide for the treatment of refractory lower bowel manifestations of systemic sclerosis.

BACKGROUND: Lower gastrointestinal (GI) tract involvement can affect up to 50% of systemic sclerosis (SSc) patients, and may result in malabsorption, pseudo-obstruction, hospitalization, and death. We report our experience with linaclotide, a selective agonist of guanylate cyclase C (GC-C), for SSc patients with refractory lower GI disease. METHODS: We performed an analysis of patients seen at the Johns Hopkins Scleroderma Center and identified patients prescribed linaclotide for refractory lower GI manifestations. Patients had clinical data collected in our longitudinal database. Linaclotide responders were on medication for at least 12 months with documented effectiveness by the treating physician. RESULTS: Thirty-one patients with SSc were treated with linaclotide. At the time of linaclotide initiation, 23 of these patients (74%) were classified as having severe GI disease, as defined by recurrent pseudo-obstruction, malabsorption, and/or need for artificial nutrition (Medsger GI severity score ≥ 3). The majority of patients (90.3%; 28/31) had a treatment response, while only three patients (9.7%) reported ineffectiveness or intolerable side effects. Low-dose linaclotide (≤ 145 mcg daily) was used in 18 patients and was effective in 94%. High-dose therapy (> 145 mcg daily) was effective in 11 of 13 patients (85%). Common side effects were diarrhea, cramping, or bloating (11/31, 35%). Ineffectiveness, cost, and abdominal pain were complaints cited among those who discontinued therapy. CONCLUSION: Linaclotide is a well-tolerated and efficacious pro-secretory and pro-motility agent that can be used to manage refractory lower GI manifestations in SSc. We found that low-dose linaclotide is an effective option and may be better tolerated, though a subset of patients may require high dose regimens.

Outcomes of flexor digitorum longus (FDL) tendon transfer in the treatment of Achilles tendon disorders.

BACKGROUND: In patients with chronic Achilles tendon disorders, Achilles tendon debridement can be supplemented with a tendon transfer, with the flexor hallucis longus tendon (FHL) transfer representing the most common used technique. Our study describes clinical and functional results of patients treated with flexor digitorum longus (FDL) tendon transfer in the treatment of patients with chronic Achilles tendon disorders. METHODS: Retrospective study of prospectively collected data of thirteen patients (15 feet) that underwent FDL tendon transfer as part of the treatment of chronic Achilles tendon disorders. Preoperative and postoperative assessment included visual analogue score (VAS) for pain, SF-36 survey and lower extremity functional scale (LEFS). The average follow-up was 26.4 (range, 14-56) months. Patients were also assessed for ability to perform single leg heel rise test, muscle power for plantar flexion of the lesser toes, surgical scar condition and associated complications. RESULTS: At final follow-up, we found significant postoperative improvement in VAS score (6.6 ±â€¯2.99 vs 1.06 ±â€¯1.43; p < .0001), SF-36 physical component summary (PCS) (28.20 ±â€¯10.71 vs 45.04 ±â€¯11.19; p < .0001) and LEFS (36.13 ±â€¯20.49 vs 58.73 ±â€¯18.19; p < .0001). Twelve patients (92%) could perform a single leg heel rise test in the operated extremity, although there was significant difference when comparing operated and uninvolved sides (4.86 ±â€¯3.36 cm vs 7.18 ±â€¯3.40 cm; p = .0002). One patient reported weakness for plantar flexion of the lesser toes, without balance or gait disturbances. Two patients (2 feet, 13.3%) had superficial infections and one patient (one foot, 6.6%) needed operative debridement for a deep infection. CONCLUSIONS: FDL tendon transfer represent an operative alternative in the treatment of chronic Achilles tendon disorders. Our study showed good clinical outcomes with low complications and donor site morbidity. LEVEL OF EVIDENCE: Observational study, case series - level IV.

Influence of investigator experience on reliability of adult acquired flatfoot deformity measurements using weightbearing computed tomography.

BACKGROUND: Our purpose was to assess the reliability of measurements of adult-acquired flatfoot deformity (AAFD) taken by investigators of different levels of clinical experience using weightbearing computed tomography (WBCT). METHODS: Nineteen AAFD patients underwent WBCT. Three investigators with different levels of clinical experience made AAFD measurements in axial, coronal, and sagittal planes. Intra- and interobserver reliability were assessed. Mean values for each measurement were compared between investigators. RESULTS: After a training protocol, substantial to perfect intra- and interobserver reliability was observed for most measures, regardless of the investigator's experience level. Significant differences between investigators were observed in 2 of 21 measured parameters: medial cuneiform-first metatarsal angle (P=0.003) and navicular-medial cuneiform angle (P=0.001). CONCLUSIONS: AAFD radiographic measurements can be performed reliably by investigators with different levels of clinical experience using WBCT. LEVEL OF EVIDENCE: Level II, prospective comparative study.

☆Diagnostic and therapeutic injections of the foot and ankle-An overview.

Foot and ankle injections are useful diagnostic and therapeutic tools, particularly when the pain etiology is uncertain. A variety of foot and ankle injuries and pathologies, including degenerative joint disease, plantar fasciitis and different tendinopathies are amenable to injections. Understanding the foot and ankle anatomical landmarks, a thorough physical exam and knowledge of the different injection techniques is key for a successful approach to different pathologies. The objective of this study is to review the use of foot and ankle injections in the orthopaedic literature, present the readers with the senior author's experience and provide a comprehensive clinical guideline to the most common foot and ankle diagnostic and therapeutic injections.

Pericarditis in Lupus.

Pericarditis is a common cardiac manifestation in systemic lupus erythematosus (SLE). Serositis is recognized in the ACR, SLICC, and EULAR/ACR classification criteria. We reviewed the prior research regarding the epidemiology, risk factors, presentation, and treatment of pericarditis in SLE.

Sonographic Findings in Inflammatory Arthritis Secondary to Immune Checkpoint Inhibition: A Case Series.

OBJECTIVE: Immune checkpoint inhibitors (ICI) are transforming the field of oncology, leading to tumor regression in multiple advanced cancers. With this case series, we review the ultrasound imaging findings in a series of patients with ICI-induced inflammatory arthritis (IA), a novel rheumatic disease that is caused by cancer immunotherapy. METHODS: We identified patients with rheumatologist-diagnosed, ICI-induced IA who had musculoskeletal ultrasound performed for clinical care. A retrospective chart review was done to obtain demographics, oncologic history, clinical presentation, imaging, and synovial fluid results. Ultrasound images were reviewed and scored for synovial and tendon pathology, presence of Doppler, and bony erosion. RESULTS: Nine patients were included in this study with a total of 18 joint regions assessed. The knees were the most commonly imaged joint followed by the hands, wrists, feet, and ankles. Synovitis was seen in 12 of the 18 joints with active Doppler in 50% of the cases. Tendon involvement was also frequently seen (13 of 18 joints) with tenosynovitis, tendinitis, and enthesophytes. Erosions were less frequent and seen in only three cases but were also an early finding. CONCLUSION: Patients with ICI-induced IA had a wide range of pathology affecting the synovium, tendons, and bones on musculoskeletal ultrasound. Further systematic study with imaging is needed for this group of diseases.

Evaluation of risk factors for pseudo-obstruction in systemic sclerosis.

OBJECTIVE: Although up to 90% of systemic sclerosis (SSc) patients are affected by gastrointestinal (GI) dysmotility, the clinical phenotype of patients with pseudo-obstruction is not well-defined. We sought to identify this phenotype by studying a large cohort of SSc patients with and without pseudo-obstruction. METHODS: We performed a retrospective analysis of patients seen at the Johns Hopkins Scleroderma Center between February 2003 and September 2017. All SSc patients had clinical data prospectively collected in a longitudinal database. Cross-sectional analyses were performed comparing autoantibody status and clinical and demographic features of patients with and without pseudo-obstruction. Cox proportional hazards regression was used to identify risk factors for pseudo-obstruction. RESULTS: 175 patients with SSc had a history of pseudo-obstruction, and 2,637 SSc patients did not. After adjusting for significant variables from the univariate analysis and potential confounders, the Cox proportional hazards multivariable analysis demonstrated that older age (HR 1.02; 95%CI 1.00-1.04), male sex (HR 1.75; 95%CI 1.42-2.43), diffuse cutaneous disease (HR 2.52; 95%CI 1.59-3.99), myopathy (HR 1.83, 95%CI 1.09-3.08), and opioid use (HR 2.38; 95%CI 1.50-3.78) were predictive of pseudo-obstruction. Autoantibodies to RNA polymerase-3 were negatively associated with pseudo-obstruction (HR 0.34; 95%CI 0.17-0.66). CONCLUSION: We identified clinical features associated with pseudo-obstruction in a large US SSc cohort. This study identifies characteristics of patients with SSc who are at a higher risk of developing pseudo-obstruction and suggests that opioids may be a modifiable risk factor. These clinical features may allow for earlier diagnostic evaluation and/or therapeutic intervention for patients at risk for pseudo-obstruction.

Spontaneous pneumomediastinum in limited cutaneous systemic sclerosis and myositis overlap.

A 58-year-old man with limited cutaneous systemic sclerosis and myositis overlap complicated by interstitial lung disease presented with several months of progressive dyspnoea and weakness. CT chest revealed extensive pneumomediastinum that was not present on imaging 6 months before this study and appeared to be spontaneous, with no preceding trauma, infection or invasive procedures.

Ranolazine-induced Elevation of Creatinine Kinase in the Absence of Statin Usage.

Ranolazine received Food and Drug Administration (FDA) approval in 2006 for the treatment of chronic angina. Ranolazine has previously been linked to the development of statin-induced myopathy, because it also inhibits CYP3A4, which increases serum statin levels. In the absence of concomitant statin therapy, elevated creatinine kinase (CK) and myalgias on ranolazine monotherapy has never been reported.

Double-positive with positive anti-glomerular basement membrane antibody and ANCA-positive disease in a patient with dermatomyositis.

Approximately one in four patients (23.3%) with inflammatory myositis including dermatomyositis can require evaluation for acute kidney injury. The main cause of kidney injury is acute tubular necrosis from medications or myoglobinuria, though clinicians should be aware of a wide variety of possible aetiologies. We present the case of a 44-year-old woman with stable anti-Jo1 dermatomyositis, who presented with acute kidney injury. During her hospital course, she was diagnosed with double-positive disease characterised by circulating anti-glomerular basement membrane antibody and myeloperoxidase antineutrophil cytoplasmic antibody and renal biopsy revealing crescentic glomerulonephritis with linear staining of capillary wall for IgG.

Anakinra for Recurrent Fevers in Systemic Lupus Erythematosus.

Fever is a common manifestation in systemic lupus erythematosus (SLE) and may be associated with disease activity, but should be closely evaluated for infection, drug reaction, thromboembolism, malignancy, or other etiology. We present the case of a 44-year-old Peruvian female with SLE with periodic high fevers and elevated high-sensitivity C-reactive protein (hs-CRP) levels, treated with anakinra, an interleukin-1 (IL-1) inhibitor. Following the birth of her first child, she developed frequent episodic fevers followed by multiple hospitalizations, approximately two to three times per year. She was started on anakinra in September 2016 and had improvement of fevers and joint symptoms. On 26-month follow-up, she had one episode of fever with bandemia requiring hospitalization but otherwise remained afebrile with a significant drop in CRP. Anakinra is well-tolerable and safe due to a short half-life. We report that the inhibition of IL-1 may be a safe and effective treatment for recurrent fevers in SLE.

Basic Science Research Trends in Orthopedic Surgery: An Analysis of the Top 100 Cited Articles.

BACKGROUND: Much of current clinical orthopedics traces its origin to basic science investigation of cellular and biochemical pathways, tissue engineering, and biomechanics of bone and joint physiology in animal and cadaveric models. QUESTIONS/PURPOSES: We sought to describe research trends in highly cited basic science studies in orthopedics. METHODS: By searching Web of Science, we identified the 100 most cited basic science orthopedics articles and focused on author position and degree (PhD, MD, or MD/PhD), topic, type of study, country, institution, and citation trends. RESULTS: These articles were published from 1970 to 2008 (citation range, 330 to 2111), with the majority from the USA (78). While there was no correlation between years since publication and total citations, more recent articles had higher citation rates. There were 38 unique first authors represented, with Caplan, Harris, Mankin, Noyes, and Warren as primary authors or co-authors of four articles each. Twelve journals published these 100 articles, with the majority in Journal of Bone and Joint Surgery (46) and Clinical Orthopaedics and Related Research (18). Frequent topics included biomechanics (31), healing/regeneration (21), and cellular/molecular biology (13). The Hospital for Special Surgery/Cornell University (10) published the most, followed by the Hospital for Joint Diseases/New York University (6), and University of Pittsburgh (6). No difference was observed in total citations and average citation rate by author degree. Eight articles were contributed from privately owned institutions or industry, with the rest from academic hospitals. CONCLUSION: This review may aid those seeking insight into landmark studies and future direction of basic science research in orthopedics.

Mycophenolate Mofetil in a Lupus Patient with Pulmonary Hypertension.

Pulmonary hypertension (PH) is a life-threatening complication of several, different connective tissue diseases, including systemic lupus erythematous (SLE), systemic sclerosis, and rheumatoid arthritis. PH can present early in SLE. The severity does not correlate with other organ disease activity or with disease duration. It is still debatable whether immunosuppressive therapy is useful for PH related to SLE or autoimmune connective tissue disease, as there are no large clinical trials. However, several case reports have shown improvement with cyclophosphamide and prednisone with or without vasodilator therapy. We present a case of SLE-related PH in which a dramatic improvement in mean pulmonary artery pressure and exercise capacity was noted after the institution of treatment with mycophenolate mofetil, resulting in a decrease in corticosteroid dose. Our observations support the potential value of mycophenolate mofetil therapy for PH in SLE.

Resection of a Giant-Cell Tumor of the Proximal Aspect of the Radius with Osteoarticular Allograft Reconstruction: A Case Report.

CASE: Giant-cell tumors are locally aggressive osteolytic benign tumors that are characterized by multinucleated giant cells. Recurrence rates are ≤30% after curettage and <5% after resection, but reconstruction can be difficult. We describe an osteoarticular allograft reconstruction of the proximal aspect of the radius in a 23-year-old man after resection of a giant-cell tumor. CONCLUSION: Five months after surgery, the patient had satisfactory joint articulation, range of motion, and strength, with no signs of hardware or graft failure. By 17 months, there was complete osseous union. The joint remained stable at 54 months. We describe our surgical approach, which restores joint stability and minimizes recurrence.

Diagnostic Injections About the Shoulder.

Injections about the shoulder serve diagnostic as well as therapeutic purposes. Diagnosis of shoulder conditions, such as rotator cuff tears, acromioclavicular joint pathology, subacromial impingement or anterolateral pain syndrome, glenohumeral joint pathology, suprascapular nerve entrapment, and biceps tendon pathologies, is often complicated by concomitant conditions with overlapping symptoms and by inconclusive physical examination and imaging results. Injections of anesthetic agents can often help clinicians locate the source of pain. However, technique and accuracy of needle placement can vary by route. Accuracy is often improved with the use of ultrasonography guidance, although studies differ on the benefits of guided versus unguided injection.

Two Cases of Sinusitis Induced by Immune Checkpoint Inhibition.

We report the acute onset of aseptic sinusitis in 2 patients receiving the immune checkpoint inhibitors, ipilimumab and nivolumab, for treatment of metastatic melanoma. Ipilimumab, a monoclonal antibody targeting cytotoxic T-lymphocyte antigen-4, and nivolumab, targeting programmed cell death-1, have been associated with numerous immune-related adverse events. To the authors' knowledge, this is the first report of aseptic sinusitis as a consequence of immune checkpoint inhibition therapy.

Outcomes After Interpositional Arthroplasty of the First Metatarsophalangeal Joint.

BACKGROUND: For patients with hallux rigidus seeking a motion-sparing procedure, interposition arthroplasty is an alternative to fusion. The purpose of this study was to report patient outcomes after interpositional arthroplasty for hallux rigidus. METHODS: All patients undergoing interpositional arthroplasty at our institution from 2001 to 2014 were identified and a retrospective chart review was performed. Follow-up was conducted through a telephone survey to obtain survivorship, satisfaction, and functional scores. Survivorship of the interpositional arthroplasty procedure was defined as no subsequent surgery on the hallux after the index procedure. Patients were excluded for incomplete records. Complications were recorded. From 2001 to 2014, 183 patients were identified. Of these, 14 were excluded for incomplete data, leaving 169 patients. Of these, 133 had an average follow-up of 62.2 months (range, 24.3 months to 151.2 months). RESULTS: The overall failure rate was 3.8% (5/133). Patient-reported outcome was rated as excellent in 65.4% (87/133) or good in 24.1% (32/133) of patients and fair or poor in 10.5% (14/133) of patients. Of 133 patients, 101 (76%) were able to return to fashionable or regular footwear. The infection rate was 1.5% (2/133). Patient-reported cock-up deformity of the first metatarsophalangeal joint (MTPJ) occurred in 4.5% (6/133) of patients. In addition, 17.3% (23/133) of patients reported metatarsalgia of the second or third MTPJ at the time of final follow-up, and there was no significant difference between interposition types ( P = .441). CONCLUSION: Interpositional arthroplasty for hallux rigidus was found to have excellent or good results in most patients at a mean follow-up of 62.2 months. LEVEL OF EVIDENCE: Level IV, retrospective case series.

Cutaneous burn caused by radiofrequency ablation probe during shoulder arthroscopy.

It is common in shoulder surgery to perform an arthroscopic acromioplasty for patients with varying degrees of rotator cuff disease. One method for helping the surgeon stay oriented to the location of the arthroscopic instruments during this procedure is to place spinal needles into the subacromial space to demarcate bony landmarks. It is also common during arthroscopic partial acromioplasty to use an electrocautery device for hemostasis and tissue ablation. Although many complications of using an electrothermal device have been described, this is the first published report of a skin burn from direct contact of the device with the spinal needle used for demarcation during acromioplasty. We report this case to highlight the need to take precautions to prevent the metal needles used in arthroscopic surgery from overheating by contact with an ablation device.