Management guideline for Werner syndrome 2020. 7. Skin ulcer associated with Werner syndrome: Dermatological treatment

Skin ulcers in Werner's syndrome often arise from hyperkeratotic lesions and trauma to pressure points such as the plantar region, and are more difficult to treat than wound healing in healthy individuals. Multiple factors contribute to the intractable skin ulcers in Werner's syndrome, including skin thinning, sclerosis, fatty tissue loss, impaired blood flow, calcification, and excessive pressure due to osteoarticular deformity. Treatment includes topical application of a keratolytic agent for keratosis around the ulcer. Treatment of ulcers is the same as for normal ulcers, and if the ulcer is associated with infection and necrotic tissue, surgical debridement with a scalpel or scissors should be performed as much as possible after washing with saline or mildly warm water or with an antibacterial agent. Topical medications that promote softening and debridement of the necrotic tissue are used with careful control of moisture in the wound. Topical agents that promote granulation should be used in wounds where necrotic tissue has been removed without infection. Dressings to maintain a moist environment in the wound may also be useful. If the wound does not improve with conservative treatment, surgical treatment should be considered. Geriatr Gerontol Int 2021; 21: 160–162 .     

Primary lung cancer associated with Werner syndrome

A 52‐year‐old man with Werner Syndrome (WS) was admitted to our hospital for the treatment of skin ulcers on his thighs. Routine chest radiography revealed an abnormal shadow in the left upper lung field. Computed tomography (CT) revealed a poorly demarcated homogeneous mass (diameter, 4 cm) in the S1 + 2 lung area; no pleural effusion was observed. CT‐guided percutaneous needle biopsy revealed the presence of an adenocarcinoma. Other imaging studies did not reveal any lymph‐node involvement or presence of metastatic lesions. The patient was diagnosed with stage IB adenocarcinoma (T2N0M0), and a left upper lobectomy was successfully carried out; postoperative wound healing was steady and uneventful, with no obvious ulcer formation. Primary lung cancers very rarely develop in patients with WS; non‐epithelial tumors are usually observed in such patients. Patients with WS usually develop severe skin problems, such as refractory skin ulcers in the extremities; however, our patient did not develop any skin‐related complications after surgery. As the expected lifespan of patients with WS is increasing, we need to pay attention not only to the rare non‐epithelial malignancy, but also cancer. Further, the expected short lifespan of patients with WS, as well as the possibility of skin‐related problems after surgery, should not be considered while deciding whether to take the option of surgery in the case of malignancy. Geriatr Gerontol Int 2010; 10: 319–323.     

Levofloxacin-induced Achilles tendon rupture in a patient with systemic microscopic polyangiitis

We report a case of spontaneous Achilles tendon rupture associated with myeloperoxidase–anti-neutrophil cytoplasmic antibody (MPO-ANCA)-related microscopic polyangiitis in a 77-year-old man who was treated with oral corticosteroids. Several days after 10 days of treatment with levoflaxacin (daily dose 200 mg) for bacterial pneumonia, he noted discomfort around both Achilles tendons. The discomfort developed into swelling around his left ankle, and he could not walk well. We diagnosed bilateral Achilles tendinitis with spontaneous rupture induced by levofloxacin. Epidemiological studies show that the risk of fluoroquinolone-related tendon rupture is highest among patients over the age of 60 years who are receiving a corticosteroid. Rupture of the Achilles tendon is a rare but serious side effect of fluoroquinolone usage. Thus, physicians should be aware of this adverse effect, especially when prescribing medication for aged patients being treated with corticosteroids.     

Levofloxacin-induced Achilles tendon rupture in a patient with systemic microscopic polyangiitis

Abstract

We report a case of spontaneous Achilles tendon rupture associated with myeloperoxidase–anti-neutrophil cytoplasmic antibody (MPO-ANCA)-related microscopic polyangiitis in a 77-year-old man who was treated with oral corticosteroids. Several days after 10 days of treatment with levoflaxacin (daily dose 200?mg) for bacterial pneumonia, he noted discomfort around both Achilles tendons. The discomfort developed into swelling around his left ankle, and he could not walk well. We diagnosed bilateral Achilles tendinitis with spontaneous rupture induced by levofloxacin. Epidemiological studies show that the risk of fluoroquinolone-related tendon rupture is highest among patients over the age of 60 years who are receiving a corticosteroid. Rupture of the Achilles tendon is a rare but serious side effect of fluoroquinolone usage. Thus, physicians should be aware of this adverse effect, especially when prescribing medication for aged patients being treated with corticosteroids.     

Biomarkers of Vascular Calcification and Mortality in Patients with ESRD

Background

Vascular calcification is common among patients undergoing dialysis and is associated with mortality. Factors such as osteoprotegerin (OPG), osteopontin (OPN), bone morphogenic protein-7 (BMP-7), and fetuin-A are involved in vascular calcification.

Design, setting, participants, & measurements

OPG, OPN, BMP-7, and fetuin-A were measured in blood samples from 602 incident dialysis patients recruited from United States dialysis centers between 1995 and 1998 as part of the Choices for Healthy Outcomes In Caring for ESRD Study. Their association with all-cause and cardiovascular mortality were assessed using Cox proportional hazards models adjusted for demographic characteristics, comorbidity, serum phosphate, and calcium. An interaction with diabetes was tested because of its known association with vascular calcification. Predictive accuracy of selected biomarkers was explored by C-statistics in nested models with training and validation subcohorts.

Results

Higher OPG and lower fetuin-A levels were associated with higher mortality over up to 13 years of follow-up (median, 3.4 years). The adjusted hazard ratios (HR) for highest versus lowest tertile were 1.49 (95% confidence interval [95% CI], 1.08 to 2.06) for OPG and 0.69 (95% CI, 0.52 to 0.92) for fetuin-A. In stratified models, the highest tertile of OPG was associated with higher mortality among patients without diabetes (HR, 2.42; 95% CI, 1.35 to 4.34), but not patients with diabetes (HR, 1.26; 95% CI, 0.82 to 1.93; P for interaction=0.001). In terms of cardiovascular mortality, higher fetuin-A was associated with lower risk (HR, 0.85 per 0.1 g/L: 95% CI, 0.75 to 0.96). In patients without diabetes, higher OPG was associated with greater risk (HR for highest versus lowest tertile, 2.91; 95% CI, 1.06 to 7.99), but not in patients with diabetes or overall. OPN and BMP-7 were not independently associated with outcomes overall. The addition of OPG and fetuin-A did not significantly improve predictive accuracy of mortality.

Conclusions

OPG and fetuin-A may be risk factors for all-cause and cardiovascular mortality in patients undergoing dialysis, but do not improve risk prediction.     

Primary liver tumor associated with Werner syndrome (adult progeria)

A 57‐year‐old woman was admitted to our hospital with characteristic aging of the face and thin body. Before admission, she had been treated for diabetes mellitus type 2 and had undergone amputation of the right leg due to ischemic disease. Abdominal computed tomography revealed primary liver tumor. Biopsy of the liver mass revealed poorly differentiated adenocarcinoma, not hepatocellular carcinoma. Genetic sequencing indicated a homozygous mutation in the Werner syndrome gene (WRN) and she was diagnosed with Werner syndrome with primary liver tumor. She declined medications for the liver tumor and eventually died 6 months after diagnosis. Werner syndrome is a rare autosomal recessive disorder associated with premature aging, and most cases of Werner syndrome have been reported from Japan. The main causes of death with Werner syndrome are malignancy and atherosclerotic vascular disease. With respect to malignancy, non‐epithelial tumors are more common in Werner syndrome patients than in the general population. Some cases also show complications of epithelial tumors, as in the present case. When a liver tumor of unknown etiology is accompanied by characteristic aging of the face, Werner syndrome should be suspected and a comprehensive search for other tumors and complications of metabolic disorders undertaken.     

Atrial Fibrillation in Patients with Constrictive Pericarditis: The Significance of Pericardial Calcification

Background: Although atrial fibrillation (AF) is commonly encountered in patients with constrictive pericarditis (CP), little has been done to clarify its associated predisposing factors. Our aim was to evaluate the association of age, gender, disease duration, and pericardial calcification with AF in these patients. Methods: The medical records of 44 patients with CP were reviewed. There were 13 (29.5%) with AF and 31 (70.5%) with sinus rhythm. The two groups were compared for demographic variables, disease duration, and the presence of pericardial calcification. Results: The male‐to‐female ratio was 3.4:1. Calcification was seen in 11 (25%) of the entire group. AF was much more common in those with calcification than those with sinus rhythm (odds ratio, 7.87 [95% CI, 1.73–35.78], P = 0.008). There was no association between the presence of AF and the age (P = 0.156) or gender (P ≈ 1.00). Logistic regression, however, showed that the chance of developing AF increased by 27% by each year of increase in disease duration (P = 0.025). Conclusion: It seems that in patients with CP, the presence of pericardial calcification and the increasing disease duration are associated with a higher chance of developing AF.     

Prevalence of and Predictive Factor for Abdominal Aortic Calcification in Thai Chronic Kidney Disease Patients

Presence and severity of cardiovascular calcifications strongly predict cardiovascular morbidity and mortality in patients with CKD. This multicenter, cross‐sectional study primarily aimed to determine prevalence of abdominal aortic calcification (AAC) detected by plain lateral abdominal radiograph, and secondarily aimed to assess predictive factors for AAC. Patients (N = 1500), aged 18–70 years, with CKD stages 3–5D for ≥3 months prior to evaluation, were enrolled at 24 study centers in Thailand; 54.3% were non‐dialysis patients. The prevalence of AAC was 70.6% and 70.8% in non‐dialysis and dialysis patients, respectively. Patient's advanced age and widening pulse pressure were identified as predictive factors for AAC ≥ 5 in non‐dialysis patients, while patient's age, history of coronary heart disease or diabetes, longer dialysis vintage, and increasing corrected serum calcium or high‐sensitivity C‐reactive protein were identified as such in dialysis patients. With additional regression having covariates in binary, corrected serum calcium ≥9.5 mg/dL gave an OR 1.974 (95% CI: 1.324–2.943) for AAC ≥ 5 among the dialysis patients. AAC in diabetes subgroup (N = 692) was additionally evaluated and found that it was prevalent at 84.7% with increased phosphorus as predictive factor (OR, 1.178; 95% CI: 1.032–1.344) and 1,25 (OH)₂ vitamin D as protective factor (OR, 0.983; 95% CI, 0.970–0.996). The prevalence of AAC in the Thai CKD population is lower than that reported in the literature, and yet the burden is prominent in patients coexisting with diabetes. Variable relationships identified in this study may guide preventive measures against cardiovascular complications in CKD patients.     

Vascular Calcification in Patients with Nondialysis CKD over 3 Years

Background and objectives

Vascular calcification (VC) is common in CKD, but little is known about its prognostic effect on patients with nondialysis CKD. The prevalence of VC and its ability to predict death, time to hospitalization, and renal progression were assessed.

Design, setting, participants, & measurements

The Study of Mineral and Bone Disorders in CKD in Spain is a prospective, observational, 3-year follow-up study of 742 patients with nondialysis CKD stages 3–5 from 39 centers in Spain from April to May 2009. VC was assessed using Adragao (AS; x-ray pelvis and hands) and Kauppila (KS; x-ray lateral lumbar spine) scores from 572 and 568 patients, respectively. The primary end point was death. Secondary outcomes were hospital admissions and appearance of a combined renal end point (beginning of dialysis or drop >30% in eGFR). Factors related to VC were assessed by logistic regression analysis. Survival analysis was assessed by Cox proportional models.

Results

VC was present in 79% of patients and prominent in 47% (AS≥3 or KS>6). Age (odds ratio [OR], 1.05; 95% confidence interval [95% CI], 1.02 to 1.07; P<0.001), phosphorous (OR, 1.68; 95% CI, 1.28 to 2.20; P<0.001), and diabetes (OR, 2.11; 95% CI, 1.32 to 3.35; P=0.002) were independently related to AS≥3. After a median follow-up of 35 months (interquartile range=17–36), there were 70 deaths (10%). After multivariate adjustment for age, smoking, diabetes, comorbidity, renal function, and level of phosphorous, AS≥3 but not KS>6 was independently associated with all-cause (hazard ratio [HR], 2.07; 95% CI, 1.07 to 4.01; P=0.03) and cardiovascular (HR, 3.46; 95% CI, 1.27 to 9.45; P=0.02) mortality as well as a shorter hospitalization event–free period (HR, 1.14; 95% CI, 1.06 to 1.22; P<0.001). VC did not predict renal progression.

Conclusions

VC is highly prevalent in patients with CKD. VC assessment using AS independently predicts death and time to hospitalization. Therefore, it could be a useful index to identify patients with CKD at high risk of death and morbidity as previously reported in patients on dialysis.     

False tendons may be associated with the genesis of J-waves: Prospective study in young healthy male

Background

Recent studies showed that J-waves are associated with vulnerability to ventricular fibrillation. Recently we reported the association between false tendons (FTs) and J-waves in a retrospective study.

Methods and results

We prospectively studied 50 young healthy men (mean age 24.6 ± 2.7 years). FTs were detected echocardiographically and classified based on their points of attachment as type 1 (longitudinal type), type 2 (diagonal type), and type 3 (transverse type). J-waves were defined as terminal QRS notching or slurring with ≥ 0.1 mV. The filtered QRS duration (fQRSd), RMS40, and LAS40 were measured on signal-averaged ECGs. FTs were detected in 37 of the 50 subjects (74%). The incidence of J-waves was significantly higher in subjects with type 1 or type 2 FTs than those with no- or type 3 FTs (61% vs. 26%, p < 0.05). The leads with J-waves were closely associated with the location of the FT. While no late potential was recorded in any study subjects, fQRSd and LAS40 were significantly longer in subjects with type 1 or type 2 FTs (p < 0.05). Univariate and multivariate logistic regression analysis revealed that only the existence of FTs (type 1 or 2) was an independent predictor of the presence of J-waves.

Conclusions

Our results suggest that FTs were related to the genesis of J-waves with conduction delay.     

Spontaneous bilateral rupture of the Achilles tendon in a patient with chronic obstructive pulmonary disease

A 69-year-old man with chronic obstructive pulmonary disease (COPD) presented with an exacerbation of cough and breathlessness, as well as a 5 day history of sudden-onset bilateral calf tenderness. He had been commenced on inhaled steroids 41/2 years earlier and then received maintenance oral prednisone. Upon examination, there was a haematoma inferior to the medial malleolus with no Achilles tenderness on the left side. On the right side, there was focal tenderness over the mid-portion of the Achilles tendon with pain accentuated upon dorsi flexion. A venous duplex study confirmed superficial venous thrombosis involving the left gastrocnemius vein extending proximally to the popliteal vein junction. The major axial deep veins of the left lower leg were patent. Findings on the right side were normal. A subsequent diagnostic ultrasound demonstrated unequivocal bilateral Achilles tendon ruptures. The patient subsequently underwent corrective surgery. There have been several reports of bilateral Achilles tendon rupture associated with long-term corticosteroid use. It is likely that this entity is underdiagnosed because of a lack of awareness of this association by physicians. Recognition and surgical intervention are likely to reduce morbidity and improve outcome.     

Abnormal foot function in diabetic patients: the altered onset of Windlass mechanism.

AIM: The aim of this study was to examine foot function in the presence of diabetes-induced alterations of the anatomical and biomechanical unit formed by the Achilles tendon, plantar fascia and metatarso-phalangeal joints. More specifically, we focused on the Windlass mechanism, the physiological mechanism which entails stiffening of the foot during propulsion. METHODS: Sixty-one diabetic patients, with or without neuropathy, and 21 healthy volunteers were recruited. The thickness of Achilles tendon and plantar fascia was measured by ultrasound. The main biomechanical parameters of foot-floor interaction during gait were acquired by means of dedicated platforms. The range of motion of the 1st metatarso-phalangeal joint was measured passively. RESULTS: The plantar fascia (PF) and Achilles tendon (AT) were significantly thickened in diabetic patients [control subjects: PF 2.0+/-0.5 mm, AT 4.0+/-0.5 mm; diabetic patients without neuropathy: PF 2.9+/-1.2 mm (P=0.002), AT 4.6+/-1.0 mm (P=0.016); diabetic patients with neuropathy: PF 3.0+/-0.8 mm (P<0.0001), AT 4.9+/-1.7 mm (P=0.026)]. Joint mobility was significantly reduced [control subjects: 100.0+/-10.0 degrees; diabetic patients without neuropathy: 54.0+/-29.4 degrees (P<0.0001); diabetic patients with neuropathy: 54.9+/-17.2 degrees (P<0.0001)]. Loading times and force integrals under the heel and the metatarsals increased [metatarsal loading time (% stance phase): control subjects 88.2+/-4.1%; diabetic patients without neuropathy 90.1+/-4.7% (P=0.146); diabetic patients with neuropathy 91.7+/-6.6% (P=0.048)]. CONCLUSIONS: Increased thickness of Achilles tendon and plantar fascia, more evident in the presence of neuropathy, may contribute to an overall increase of tensile force and to the occurrence of an early Windlass mechanism, maintained throughout the whole gait cycle. This might play a significant role in the overall alteration of the biomechanics of the foot-ankle complex.