Intravascular lithotripsy for severe coronary calcification: a systematic review.

INTRODUCTION: Coronary artery calcification remains a challenge in percutaneous coronary interventions, due to the higher risk of suboptimal result with subsequent poor clinical outcomes. Intravascular lithotripsy is a novel way of treating severe coronary calcification as it has the ability to modify calcium both circumferentially as well as transmurally, facilitating stent expansion and apposition. We conducted a systematic overview of the published literature on intravascular lithotripsy (IVL) assessing the efficacy and feasibility of IVL in treating severe coronary calcification. EVIDENCE ACQUISITION: Of the retrieved publications, 62 met our inclusion criteria and were included. A total of 1389 patients (1414 lesions) with significant coronary calcification or under-expanded stents underwent IVL. EVIDENCE SYNTHESIS: The mean age was 72.03 years (74.7% male). There was a significant improvement in acute and sustained vessel patency, with mean minimal lumen diameter of 2.78±0.46 mm, resulting in acute gain of 1.72±0.51 mm. The acute procedural success rate was 78.2 to 100% with in-hospital complication rate of 5.6 to 7.0%. The majority of the studies reported 30-day MACE, which was between 2.2 to 7.8%. CONCLUSIONS: The recent studies have highlighted that the use of IVL with adjuvant intracoronary imaging has revolutionized the way of treating heavily calcified, non-dilatable coronary lesions and is likely to succeed the conventional ways of treating these complex lesions. We need further studies to gauge the long-term efficacy and safety of IVL against techniques currently available for calcium modification including conventional balloons, cutting or scoring balloons, rotational atherectomy and laser atherectomy.

Inflammatory and Biomechanical Drivers of Endothelial-Interstitial Interactions in Calcific Aortic Valve Disease.

Calcific aortic valve disease is dramatically increasing in global burden, yet no therapy exists outside of prosthetic replacement. The increasing proportion of younger and more active patients mandates alternative therapies. Studies suggest a window of opportunity for biologically based diagnostics and therapeutics to alleviate or delay calcific aortic valve disease progression. Advancement, however, has been hampered by limited understanding of the complex mechanisms driving calcific aortic valve disease initiation and progression towards clinically relevant interventions.

Frontiers in translational systemic sclerosis research: A focus on the unmet 'cutaneous' clinical needs (Viewpoint).

This viewpoint considers four cutaneous unmet clinical needs of patients with systemic sclerosis (SSc), namely the rapidly progressive skin thickening (scleroderma) which occurs early on in diffuse cutaneous disease; digital (finger and toe) ulcers; calcinosis; and cutaneous telangiectases. All four problems cause pain, disability and/or disfigurement, all impact on quality of life, and for each, we require effective treatments. For each unmet need, we give a brief description of the clinical problem (including clinical burden), pathophysiology and current treatment, followed by a personal viewpoint of the key questions which research must address. For the painful, debilitating skin thickening of early diffuse cutaneous SSc, studies are required to decide whether corticosteroids are effective and safe (current opinion is divided) and whether phototherapy approaches have a role. Also, we need to develop and validate reliable outcome measures for clinical trials of promising new therapies: these could be composite indices, novel non-invasive imaging methods and patient-reported outcome measures, possibly in combination as they provide complementary information. For digital ulcers, again we require validated outcome measures for clinical trials. We also need to explore local (including topical) treatments, which are free from systemic adverse effects, and preventative strategies for high-risk patients. For calcinosis, we need to better understand pathophysiology, to validate outcome measures and to develop topical treatments. For telangiectases, we need to "use" these highly accessible lesions to help unravel the vascular pathophysiology of SSc and explore their different properties as potential biomarkers.

Comparing Ultrasound-Guided Needling Combined With a Subacromial Corticosteroid Injection Versus High-Energy Extracorporeal Shockwave Therapy for Calcific Tendinitis of the Rotator Cuff: A Randomized Controlled Trial.

PURPOSE: To compare clinical and radiographic outcomes after treatment with standardized high-energy extracorporeal shock wave therapy (ESWT) and ultrasound-guided needling (UGN) in patients with symptomatic calcific tendinitis of the rotator cuff who were nonresponsive to conservative treatment. METHODS: The study was designed as a randomized controlled trial. The ESWT group received ESWT (2000 pulses, energy flux density 0.35 mJ/mm2) in 4 sessions with 1-week intervals. UGN was combined with a corticosteroid ultrasound-guided subacromial bursa injection. Shoulder function was assessed at standardized follow-up intervals (6 weeks and 3, 6, and 12 months) using the Constant Murley Score (CMS), the Disabilities of the Arm, Shoulder, and Hand questionnaire, and visual analog scale for pain and satisfaction. The size, location, and morphology of the deposits were evaluated on radiographs. The a priori sample size calculation computed that 44 participants randomized in each treatment group was required to achieve a power of 80%. RESULTS: Eighty-two patients were treated (56 female, 65%; mean age 52.1 ± 9 years) with a mean baseline CMS of 66.8 ± 12 and mean calcification size of 15.1 ± 4.7 mm. One patient was lost to follow-up. At 1-year follow-up, the UGN group showed similar results as the ESWT group with regard to the change from baseline CMS (20.9 vs 15.7; P = .23), Disabilities of the Arm, Shoulder, and Hand questionnaire (-20.1 vs -20.7; P = .78), and visual analog scale for pain (-3.9 and -2.6; P = .12). The mean calcification size decreased by 13 ± 3.9 mm in the UGN group and 6.7 ± 8.2 mm in the ESWT group (

Shock wave therapy for rotator cuff disease with or without calcification.

BACKGROUND: Shock wave therapy has seen widespread use since the 1990s to treat various musculoskeletal disorders including rotator cuff disease, but evidence of its efficacy remains equivocal. OBJECTIVES: To determine the benefits and harms of shock wave therapy for rotator cuff disease, with or without calcification, and to establish its usefulness in the context of other available treatment options. SEARCH METHODS: We searched Ovid MEDLINE, Ovid Embase, CENTRAL, ClinicalTrials.gov and the WHO ICTRP up to November 2019, with no restrictions on language. We reviewed the reference lists of retrieved trials to identify potentially relevant trials. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and controlled clinical trials (CCTs) that used quasi-randomised methods to allocate participants, investigating participants with rotator cuff disease with or without calcific deposits. We included trials of comparisons of extracorporeal or radial shock wave therapy versus any other intervention. Major outcomes were pain relief greater than 30%, mean pain score, function, patient-reported global assessment of treatment success, quality of life, number of participants experiencing adverse events and number of withdrawals due to adverse events. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies for inclusion, extracted data and assessed the certainty of evidence using GRADE. The primary comparison was shock wave therapy compared to placebo. MAIN RESULTS: Thirty-two trials (2281 participants) met our inclusion criteria. Most trials (25) included participants with rotator cuff disease and calcific deposits, five trials included participants with rotator cuff disease and no calcific deposits, and two trials included a mixed population of participants with and without calcific deposits. Twelve trials compared shock wave therapy to placebo, 11 trials compared high-dose shock wave therapy (0.2 mJ/mm² to 0.4 mJ/mm² and above) to low-dose shock wave therapy. Single trials compared shock wave therapy to ultrasound-guided glucocorticoid needling, ultrasound-guided hyaluronic acid injection, transcutaneous electric nerve stimulation (TENS), no treatment or exercise; dual session shock wave therapy to single session therapy; and different delivery methods of shock wave therapy. Our main comparison was shock wave therapy versus placebo and results are reported for the 3 month follow up. All trials were susceptible to bias; including selection (74%), performance (62%), detection (62%), and selective reporting (45%) biases. No trial measured participant-reported pain relief of 30%. However, in one trial (74 participants), at 3 months follow up, 14/34 participants reported pain relief of 50% or greater with shock wave therapy compared with 15/40 with placebo (risk ratio (RR) 1.10, 95% confidence interval (CI) 0.62 to 1.94); low-quality evidence (downgraded for bias and imprecision). Mean pain (0 to 10 scale, higher scores indicate more pain) was 3.02 points in the placebo group and 0.78 points better (0.17 better to 1.4 better; clinically important change was 1.5 points) with shock wave therapy (9 trials, 608 participants), moderate-quality evidence (downgraded for bias). Mean function (scale 0 to 100, higher scores indicate better function) was 66 points with placebo and 7.9 points better (1.6 better to 14 better, clinically important difference 10 points) with shock wave therapy (9 trials, 612 participants), moderate-quality evidence (downgraded for bias). Participant-reported success was reported by 58/150 people in shock wave therapy group compared with 35/137 people in placebo group (RR 1.59, 95% CI 0.87 to 2.91; 6 trials, 287 participants), low-quality evidence (downgraded for bias and imprecision). None of the trials measured quality of life. Withdrawal rate or adverse event rates may not differ between extracorporeal shock wave therapy and placebo, but we are uncertain due to the small number of events. There were 11/34 withdrawals in the extracorporeal shock wave therapy group compared with 13/40 withdrawals in the placebo group (RR 0.75, 95% CI 0.43 to 1.31; 7 trials, 581 participants) low-quality evidence (downgraded for bias and imprecision); and 41/156 adverse events with extracorporeal shock wave therapy compared with 10/139 adverse events in the placebo group (RR 3.61, 95% CI 2.00 to 6.52; 5 trials, 295 participants) low-quality evidence (downgraded for bias and imprecision). Subgroup analyses indicated that there were no between-group differences in pain and function outcomes in participants who did or did not have calcific deposits in the rotator cuff. AUTHORS' CONCLUSIONS: Based upon the currently available low- to moderate-certainty evidence, there were very few clinically important benefits of shock wave therapy, and uncertainty regarding its safety. Wide clinical diversity and varying treatment protocols means that we do not know whether or not some trials tested subtherapeutic doses, possibly underestimating any potential benefits. Further trials of extracorporeal shock wave therapy for rotator cuff disease should be based upon a strong rationale and consideration of whether or not they would alter the conclusions of this review. A standard dose and treatment protocol should be decided upon before further research is conducted. Development of a core set of outcomes for trials of rotator cuff disease and other shoulder disorders would also facilitate our ability to synthesise the evidence.

Milia-like idiopathic calcinosis cutis of the forehead in an adult without Down's syndrome successfully treated with a CO2 laser.

BACKGROUND: Idiopathic calcinosis cutis is an uncommon form of calcinosis cutis. It may present as tumoral calcinosis, subepidermal calcified nodules or scrotal calcinosis. Subepidermal calcified nodules may also present as milia-like lesions commonly seen in children with Down's syndrome in the absence of tissue damage or metabolic disorders, it has been seldom reported in adults. The treatment of choice is surgical excision. However, a surgical approach may not always be beneficial to the patient given the cosmetic outcomes. Here, we describe the successful use of a CO2 laser in the treatment of milia-like calcinosis cutis of the forehead in an adult without Down's syndrome. AIMS: To describe the treatment of Milia-like idiopathic calcinosis cutis of the forehead in an adult without Down's syndrome successfully treated with a CO2 laser. METHODS: We report a case of a 48-year-old man who presented with skin-colored hard asymptomatic papules on the forehead that started about 9 years ago, a biopsy was performed and a diagnosis of milialike calcinosis cutis was made. Surgical excision was discarded regarding the location and the number of lesions, instead, a CO2 laser was used to treat this condition. RESULTS: Successful laser excision of the lesions with appealing cosmetic results. CONCLUSIONS: CO2 laser seems to be a valuable tool to treat milia-like calcinosis cutis lesions.

Ultrasound-guided percutaneous irrigation of calcific tendinopathy: technical developments.

Rotator cuff calcific tendinopathy (RCCT) is a common and painful shoulder disease characterised  by deposition of calcium into the rotator cuff's tendond. Different therapeutic options have been proposed, but the ultrasound-guided percutaneous irrigation (US-PICT) is been proved as an effective and safe first-line treatment. It can be performed with a single- of a double-needle tecnique, using warm saline solution to improve the dissolution of the calcific deposit. The procedure is ended with an intrabursal injection of local anaesthetics and slow-release steroids to improve the pain relief and to prevent complications. US-PICT leads to significative improvement in the shoulder funtion and pain relief in the short and long term, with a low complications rate.

Periarticular calcification mimicking inflammatory polyarthritis in chronic kidney disease.

Periarticular calcification is a frequent radiographic manifestation in chronic kidney disease (CKD). However, clinical presentation as inflammatory periarthritis, tenosynovitis, and bursitis is unusual. A 34-year-old man with CKD on dialysis for three years presented with painful swollen joints. His adherence to regular dialysis, phosphate binders, Vitamin D supplements, and antihypertension therapy was poor. He had swelling of the right thumb, index, and little fingers; periarticular swelling of the left middle finger and right little toe; and extensor tenosynovitis of the wrists and right olecranon bursitis. Laboratory investigations showed the following: urea 36 mmol/L; creatinine 1764 umol/L; serum urate 0.37 mmol/L; corrected calcium 1.76 mmol/L; phosphate 4.32 mmol/L; 25-dihydroxycholecalciferol 30 ng/mL; and parathyroid hormone 104 pmol/L. Radiographs showed periarticular calcification corresponding to the sites of inflammation. The inflammation resolved with oral steroids. In our patient, deranged mineral and bone metabolism contributed to periarticular calcification at multiple sites, mimicking inflammatory polyarthritis.

Electroacupuncture for the Treatment of Calcific Tendonitis. A Pilot Study.

Current treatment for calcific tendonitis consists of arm rest, antiinflammatory medications, and corticosteroid injections. If unsuccessful, a lot of clinicians suggest several physiotherapy modalities, such as shockwave therapy and electrotherapy. The purpose of our study was to assess the efficacy of electroacupuncture, as a substitute for failed medical treatment in calcific tendonitis. In a pilot study, we prospectively followed 10 patients treated with electroacupuncture for calcific tendonitis who failed to respond to medical treatment. Its efficacy was assessed by evaluating the level of pain, the Beck Depression Inventory, the range of active elbow mobility, and by repeated radiological evaluation of the course of calcific deposits. All clinical and radiological observations were recorded before and within 6 months after the onset of treatment. After electroacupuncture treatment (2 Hz, 180 mA for 30-60 seconds at GB21, GB34, LI4, LI 14, LI15, TW5, TW14, Chien Chien SI9, SI12, S37, S38), the visual analog score decreased notably, and the range of motion returned to normal. Radiological evaluation demonstrated almost complete absorption of calcific deposits within 6 months, after treatment. We conclude that electroacupuncture relieved skeletal pain, improved the quality of patient's life, and contributed to total regression of the calcific depositions in followed patients. So, electroacupuncture may be a valuable treatment option for calcific tendonitis, when medical treatment fails to relieve symptoms.

Pulmonary Alveolar Microlithiasis.

Pulmonary alveolar microlithiasis (PAM) is a genetic lung disorder that is characterized by the accumulation of calcium phosphate deposits in the alveolar spaces of the lung. Mutations in the type II sodium phosphate cotransporter, NPT2b, have been reported in patients with PAM. PAM progresses gradually, often producing incremental dyspnea on exertion, desaturation in young adulthood, and respiratory insufficiency by late middle age. Treatment remains supportive, including supplemental oxygen therapy. For patients with end-stage disease, lung transplantation is available as a last resort. The recent development of a laboratory animal model has revealed several promising treatment approaches for future trials.

Case report - calcification of the medial collateral ligament of the knee with simultaneous calcifying tendinitis of the rotator cuff.

BACKGROUND: Calcification of the medial collateral ligament (MCL) of the knee is a very rare disease. We report on a case of a patient with a calcifying lesion within the MCL and simultaneous calcifying tendinitis of the rotator cuff in both shoulders. CASE PRESENTATION: Calcification of the MCL was diagnosed both via x-ray and magnetic resonance imaging (MRI) and was successfully treated surgically. Calcifying tendinitis of the rotator cuff was successfully treated applying conservative methods. CONCLUSION: This is the first case report of a patient suffering from both a calcifying lesion within the medial collateral ligament and calcifying tendinitis of the rotator cuff in both shoulders. Clinical symptoms, radio-morphological characteristics and macroscopic features were very similar and therefore it can be postulated that the underlying pathophysiology is the same in both diseases. Our experience suggests that magnetic resonance imaging and x-ray are invaluable tools for the diagnosis of this inflammatory calcifying disease of the ligament, and that surgical repair provides a good outcome if conservative treatment fails. It seems that calcification of the MCL is more likely to require surgery than calcifying tendinitis of the rotator cuff. However, the exact reason for this remains unclear to date.

Ultrasound-Guided Percutaneous Tendon Treatments.

OBJECTIVE: The purpose of this article is to review currently available tendon treatments, especially those performed with sonographic guidance. CONCLUSION: Treatments of tendon disease have continued to develop and expand, and multiple therapeutic options have become available, all with varying levels of supportive clinical evidence of their efficacy. The use of ultrasound to direct these treatments improves accuracy and performance by facilitating visualization of the target and relevant adjacent structures.

Modeling pulmonary alveolar microlithiasis by epithelial deletion of the Npt2b sodium phosphate cotransporter reveals putative biomarkers and strategies for treatment.

Pulmonary alveolar microlithiasis (PAM) is a rare, autosomal recessive lung disorder associated with progressive accumulation of calcium phosphate microliths. Inactivating mutations in SLC34A2, which encodes the NPT2b sodium-dependent phosphate cotransporter, has been proposed as a cause of PAM. We show that epithelial deletion of Npt2b in mice results in a progressive pulmonary process characterized by diffuse alveolar microlith accumulation, radiographic opacification, restrictive physiology, inflammation, fibrosis, and an unexpected alveolar phospholipidosis. Cytokine and surfactant protein elevations in the alveolar lavage and serum of PAM mice and confirmed in serum from PAM patients identify serum MCP-1 (monocyte chemotactic protein 1) and SP-D (surfactant protein D) as potential biomarkers. Microliths introduced by adoptive transfer into the lungs of wild-type mice produce marked macrophage-rich inflammation and elevation of serum MCP-1 that peaks at 1 week and resolves at 1 month, concomitant with clearance of stones. Microliths isolated by bronchoalveolar lavage readily dissolve in EDTA, and therapeutic whole-lung EDTA lavage reduces the burden of stones in the lungs. A low-phosphate diet prevents microlith formation in young animals and reduces lung injury on the basis of reduction in serum SP-D. The burden of pulmonary calcium deposits in established PAM is also diminished within 4 weeks by a low-phosphate diet challenge. These data support a causative role for Npt2b in the pathogenesis of PAM and the use of the PAM mouse model as a preclinical platform for the development of biomarkers and therapeutic strategies.

An eggshell-like mineralized recurrent lesion in the popliteal region after treatment of giant cell tumor of the bone with denosumab.

We report a case of recurrent giant cell tumor of the bone (GCTB) in which treatment with denosumab gradually enhanced the eggshell-like mineralization at the periphery of the tumor. A 28-year-old male presented with a mass on his left distal femur that had enlarged within the past few months. Before curettage, GCTB of the distal femur was diagnosed based on histological analysis of a biopsy specimen; the tumor consisted of a proliferation of ovoid mononuclear stromal cells with evenly scattered multinucleated osteoclast-like giant cells. The tumor recurred three times after the initial diagnosis; at the time of the third relapse, the patient underwent en bloc resection and reconstruction with a knee joint prosthesis. He was also treated with denosumab postoperatively because some studies have recently shown the benefits of the receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitor denosumab as adjuvant therapy in patients with GCTB. Six months after starting adjuvant treatment with denosumab, radiography revealed a mineralized nodule >2 cm in diameter at the popliteal region; this lesion was considered a soft tissue recurrence of GCTB. Treatment with denosumab was continued for another 1.5 years, and the lesion was resected. Histological examination showed residual mononuclear stromal cells expressing RANKL without multinucleated giant cells surrounded by the peripheral mineralization. The patient was successfully treated by complete resection with the support of adjuvant treatment with denosumab.

Dystrophic calcification and accentuated localized Argyria after fractionated carbon dioxide laser therapy of hypertrophic scars.

IMPORTANCE: Fractionated, ultrapulsed carbon dioxide (CO2) laser therapy is a powerful tool for the treatment of scars. Common adverse effects of this therapeutic modality have been previously documented. We describe 2 unreported adverse effects of ultrapulsed CO2 laser treatment of mature scars in a patient previously treated with silver-impregnated dressings. OBSERVATIONS: A teenage survivor of toxic epidermal necrolysis presented with faint but diffuse dyschromia clinically and histologically consistent with localized argyria secondary to silver-impregnated dressings used years earlier. The patient was subsequently treated with fractionated CO2 for her scarring, but her hyperpigmentation worsened with each treatment. A subsequent biopsy specimen revealed a zone of dystrophic calcification with adjacent pseudo-ochronotic fibers that were not appreciated on biopsy specimens taken before CO2 laser treatment, suggesting unique complications not previously reported. CONCLUSIONS AND RELEVANCE: We present 2 unique complications secondary to ultrapulsed, fractionated CO2 laser treatment in a patient previously treated with silver-impregnated dressings: (1) the appearance of pseudo-ochronotic fibers in areas of worsening pigmentation and (2) evidence of dystrophic calcification limited to columns of fractionated laser ablation. Therefore, a history of argyria or treatment with silver-impregnated dressings should be considered before treatment with fractionated CO2 lasers.

Acute calcific band keratopathy: case report and literature review.

UNLABELLED: An 86-year-old patient developed a significant intraocular inflammatory reaction after having phacoemulsification. Topical therapy did not eliminate the inflammation, and tissue plasminogen activator (tPA) was injected into the anterior chamber. A white corneal plaque appeared in the previously clear cornea within days of the injection. The lesion was diagnosed as calcific band keratopathy and successfully treated with ethylenediaminetetraacetic acid chelation. Electron microscopy and elemental analysis of a corneal scraping from the lesion established its composition to be mainly calcium and phosphate, validating the diagnosis. This is the seventh reported case of rapid formation of calcific band keratopathy after tPA injection. The pathogenesis of this rare complication involves multiple factors, including alkalinization of the intraocular pH, increased phosphate concentration, and endothelial dysfunction. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Double-needle ultrasound-guided percutaneous treatment of rotator cuff calcific tendinitis: tips & tricks.

Rotator cuff calcific tendinitis is a very common disease and may result in a very painful shoulder. Aetiology of this disease is still poorly understood. When symptoms are mild, this disease may be treated conservatively. Several treatment options have been proposed. Among them, ultrasound-guided procedures have been recently described. All procedures use one or two needles to inject a fluid, to dissolve calcium and to aspirate it. In the present article, we review some tips and tricks that may be useful to improve performance of an ultrasound-guided double-needle procedure.

Submaximal suppression of parathyroid hormone ameliorates calcitriol-induced aortic calcification and remodeling and myocardial fibrosis in uremic rats.

BACKGROUND AND OBJECTIVE: In subtotally nephrectomized rats, we studied to what extent high-dose calcitriol-induced cardiovascular disease can be modulated by almost complete suppression of parathyroid hormone (PTH), mediated by either cinacalcet (CINA) or parathyroidectomy (PTX). METHODS: Five groups were studied: sham-operated controls, uremic (U), uremic with calcitriol (U+1,25D), uremic and calcitriol with CINA (U+1,25D+CINA) and uremic and calcitriol with PTX (U+1,25D+PTX). Treatments lasted 14 weeks. RESULTS: Compared with U group animals, PTH was significantly lower with calcitriol treatment and almost completely suppressed in animals treated with either PTX or CINA. Serum calcium and phosphorus levels were similarly elevated in all groups receiving calcitriol. Renal function in uremic animals was significantly more impaired in the U+1,25D group. Aortic calcifications were pronounced in U+1,25D animals and reduced by more than 50% by concomittant treatment with CINA or PTX. Chondrocytes were observed near areas of calcification (>90%) and endochondral bone formation was confirmed by positive immunofluorescence for chondrocytic transcription factor sox9 and matrix protein collagen X. Altered arterial (aneurysmatic) geometry with a significant increase in wall/lumen and lumen/body weight ratio was found only in the U+1,25D group. Myocardial fibrosis was present in all uremic groups with a significant increase in the U+1,25D group. Connective tissue growth factor messenger RNA was significantly upregulated only in the U+1,25D group. CONCLUSION: Submaximal suppression of PTH by either CINA or PTX reduced vascular calcifications, arterial remodeling and myocardial fibrosis to a similar degree and independent of the serum calcium and phosphorus levels. These data do not indicate vasculotropic effects of calcimimetics independent of PTH suppression.