Clinical and pathologic characteristics of appendiceal neuroendocrine neoplasms diagnosed during pregnancy.

Introduction: Although appendicitis occurs in approximately 1:1000 pregnancies, appendiceal neuroendocrine neoplasm (ANEN) diagnosis during pregnancy is very rare. Data on presentation, treatment and prognosis is scarce. Aim: To describe ANEN cases diagnosed during pregnancy. Materials and methods: A retrospective appraisal of 7 consecutive ANEN patients diagnosed during pregnancy from four Israeli tertiary medical centers and comparison with 17 cases described in the literature from 1965-2021. Results: Age at ANEN diagnosis was 26.4 ± 3.5 years (range 21-33). Patients were diagnosed between gestational weeks 6-40, most frequently in the third trimester (53%). The most common presenting symptom was abdominal pain. Tumor size was 14.3 ± 8.9mm (range 3-45mm). In patients from our series appendiceal base involvement was reported in 2/7; mesoappendiceal invasion in 5/7; lympho-vascular invasion in 2/7. Ki67 staining was reported in 6/7 cases and ranged from 1-10%. Pathology details were lacking in most of the previously published cases. All 7 pregnancies in our series resulted in term delivery with no complications, whereas in historical cases there were one first trimester abortion, one ectopic pregnancy, and one stillbirth. Right hemicolectomy was performed in 5/7 patients in our series and reported in 2/17 historical cases. All hemicolectomies were performed after delivery, 3-16 months after appendectomy. Local metastases were reported in two cases. Follow-up duration was 7-98 months for our patients and 3-48 months in 5 historical cases. No disease recurrence, distant metastases or mortality were noted. Conclusions: To the best of our knowledge, this is the largest series describing the extremely rare diagnosis of ANEN during pregnancy. Although pathologic characteristics varied, pregnancy outcomes were usually favorable and long-term prognosis was excellent. This data may suggest that a conservative approach to patients with ANEN diagnosis during pregnancy can be considered.

Thyroid Disorders in Patients with Systemic Sclerosis: Biochemical and Sonographic Characteristics. A Prospective Cohort Study.

BACKGROUND: Patients with systemic sclerosis (SSc) are at increased risk for autoimmune thyroid diseases, but information regarding thyroid nodules and cancer in SSc is scarce. Objectives: To evaluate the thyroid gland in patients with SSc at a single Israeli center. METHODS: Thyroid workup was conducted in consecutive SSc patients: thyroid-stimulating hormone (TSH), free thyroxine (fT4), anti-thyroid peroxidase, and anti-thyroglobulin antibodies, as well as thyroid ultrasound and fine needle aspiration (FNA) when appropriate. RESULTS: Fifty patients, mean age 51.3 ± 13.5 years (44 women) were evaluated. Ten were previously diagnosed with thyroid disease. Median TSH level was 2.0 (normal range 0.23-4 mIU/l) and median fT4 level was 1.0 (normal range 0.8-2.0 ng/dL). Among the 40 thyroid disorder-naive patients, 3 had subclinical hypothyroidism and 5 had positive anti-thyroid antibodies; 22 (44%) had 1-6 thyroid nodules, which were ≥ 1 cm in 12 (24%). Accordingly, six patients underwent FNA, and five were diagnosed as colloid nodules and one as papillary carcinoma. CONCLUSIONS: New cases of clinically significant autoimmune thyroid disease were not detected in our cohort of patients with SSc. Nevertheless, almost half had thyroid nodules. The clinical significance of these findings and their relation to thyroid cancer remains to be determined.

Osteoporosis Treatment After Osteoporotic Fractures: Data From a Single Medical Center.

OBJECTIVE: Most patients do not receive osteoporosis treatment after osteoporotic fracture. This study reviewed osteoporosis treatment after osteoporotic fractures in a center without a Fracture Liaison Service. METHODS: We identified all patients with hip, vertebral, humeral or radial fractures, evaluated in Meir Medical Center, in 2017. The exclusion criteria were not a Clalit Health Services member, high-energy fracture or 30-day postoperative mortality. The primary endpoint was osteoporosis drugs issued within 12 months of fracture. Secondary endpoints included bone densitometry and 1-year mortality. RESULTS: Five-hundred-eighty-two patients (average age 78.6 ± 11.1 years, 75.8% women) were included. There were 321 (55.5%) hip, 84 (14.1%) humeral, 33 (5.6%) vertebral, and 144 (24.7%) radial fractures. Osteoporosis drugs were issued to 26.5% of the patients; those with humeral fractures received the least (21.4%) and vertebral, the most (30.3%; P = .51). Bone densitometry was performed in 23.2% of patients. One-year mortality after hip fracture was 12.1%, followed by humeral (3.6%; P < .05). Logistic regression showed that previous treatment (odds ratio [OR] = 7.4; 95% confidence interval [CI] 3.6-15.2), bone densitometry (OR = 4.4; 95% CI 2.6-7.4) and endocrinology visit (OR = 2.6; 95% CI, 1.4-4.6) were the most important factors associated with treatment. CONCLUSION: Fewer than one third of patients received pharmacotherapy within 1 year after fracture. Because pharmacotherapy reduces future fractures and mortality, we recommend that medical staff who care for patients with fracture adopt practical and effective strategies to increase treatment rates among patients with osteoporotic fractures.

Is there an added value for whole body scan combined with stimulated thyroglobulin testing for follow-up of differentiated thyroid cancer patients?

AIM: The aim of this study was to evaluate the incidence of positive WBS in patients with negative stimulated thyroglobulin (sTg), to define the clinical characteristics of this group, and the association with disease outcome. METHODS: DTC patients who underwent surveillance with simultaneous sTg and WBS were included. RESULTS: Two hundred seventy-two patients were included. Age at diagnosis was 46.5 ± 15.2 years, 79% were female. Mean duration of follow-up was 11.6 ± 6.8 years. Patients were categorised according to stimulation test results: sTg(-)/WBS(-) in 192/272 (70.6%); sTg(+) regardless of WBS results in 33/272 (12.1%); and sTg(-)/WBS(+) in 47/272 (17.3%) subjects. sTg > 10 mg/dl was considered positive. The three groups had similar demographic and pathologic characteristics. During follow-up, additional treatment was given in 77 patients (28.3%). Twelve (4.4%) developed distant metastases; 16 patients (5.8%) died. No deaths were disease-related. There was no difference in mortality rate between categories (P = 0.182). On multivariate analysis, additional treatment was associated with male gender (P = 0.046) and positive stimulation test results, either sTg (P < 0.001) or WBS (P < 0.001). Of the 47 WBS(+)/sTg(-) patients, 7(15%) were treated due to positive WBS results, including two who underwent additional surgery. CONCLUSION: A substantial proportion of stimulation test results were discordant. There was a significant association between WBS results and administration of additional treatment. Routine WBS had additional value for a small proportion of patients with no other evidence for disease and no indication for WBS.

Long-term Bisphosphonates for Osteoporosis: A Factor Effecting Fracture Pattern?

BACKGROUND: The incidence of fragility hip fractures, intracapsular and extracapsular, has been increasing worldwide. Fracture stability is important for treatment decision-making and is related to the expected rate of complications. It is unclear whether metabolic therapy explains the increased incidence of unstable fractures. OBJECTIVES: To investigate the possible association between treatment with bisphosphonates and the various patterns encountered with intertrochanteric hip fractures. METHODS: Patients with fragility hip fractures who were treated in our department between 2013 and 2014 were included in this study. They were classified into three groups: group 1 had a stable extracapsular fracture, group 2 had an unstable extracapsular fracture, and group 3 had an intracapsular fracture. Collated data included: osteoporosis preventive therapy and duration, fracture-type, history of previous fractures, and vitamin D levels. RESULTS: Of 370 patients, 87 were previously treated with bisphosphonates (18.3% prior to fracture in group 1, 38.3% in group 2, and 13.8% in group 3). Of those treated with bisphosphonates, 56.3% had an unstable fracture, 21.8% had a stable fracture, and the rest an intracapsular fracture. In contrast, only 27.9% of patients who were not treated with bisphosphonates had an unstable fracture and 30.0% had stable fractures. CONCLUSIONS: Our findings show a higher proportion of complex and unstable fractures among patients with fragility hip-fractures who were treated with bisphosphonates than among those who did not receive this treatment. The risk for complex and unstable fracture may affect the preferred surgical treatment, its complexity, length of surgery, and rehabilitation.

Efficacy and Safety of Intravenous Pamidronate for Parathyroid Hormone-dependent Hypercalcemia in Hospitalized Patients.

CONTEXT: Bisphosphonates are effective for hypercalcemia of malignancy (HOM). Efficacy and safety data for bisphosphonates in parathyroid hormone-related hypercalcemia (PTHRH) are rare, including pamidronate (Pam), which is not indicated for this condition. OBJECTIVE: This work aims to evaluate the efficacy and safety of Pam for moderate-to-severe PTHRH. METHODS: This retrospective case-control study was conducted at a tertiary care medical center. Patients included adults hospitalized with serum calcium levels greater than 12 mg/dL, from October 29, 2013 to December 17, 2019. Etiology was categorized as PTHRH or PTH-independent. Clinical and laboratory data of PTHRH patients treated with Pam (PTHRH-Pam+) were compared to Pam-untreated counterparts (PTHRH-Pam-). RESULTS: Thirty-four patients with 37 hospitalizations for PTHRH (Pam-treated and -untreated) met the inclusion criteria. Pam was given in 24 of 37 cases (64.8%). Admission serum calcium levels for the PTHRH-Pam+ group were higher than for PTHRH-Pam- group (14.4 mg/dL vs 13.0 mg/dL, P = .005). Median total Pam dose was 60 mg (range, 30-180 mg) in the treated group. Serum calcium decreased 3.5 mg/dL for PTHRH-Pam+ vs 1.6 mg/dL for PTHRH-Pam- (P = .003). No PTHRH-Pam+ patients developed hypocalcemia or acute kidney injury. Nadir serum phosphorus levels were lower in the PTHRH-Pam+ vs PTHRH-Pam- group (1.7 mg/dL vs 2.4 mg/dL, respectively, P = .004). Three PTHRH-Pam+ patients developed severe hypophosphatemia; all resolved with intravenous and oral supplementation. Seventeen patients underwent parathyroidectomy, of whom 10 received Pam within 28 days preoperatively. Postoperatively, 4 developed hypocalcemia and 3 hypophosphatemia. CONCLUSION: This study demonstrates that Pam is effective and safe for treating PTHRH, while ensuring close laboratory monitoring of calcium and phosphorus metabolism. Larger, prospective studies are needed to establish the role of Pam and other potent bisphosphonates in moderate-to-severe PTHRH.

Temporal trends in incidence, evaluation and management of neuroendocrine neoplasms of the appendix: 14 years' experience.

BACKGROUND: Information regarding temporal trends in appendiceal neuroendocrine neoplasms (ANEN) is limited. This retrospective study evaluated temporal trends in ANEN incidence and management over a 14-year period. METHODS: Appendectomy pathology reports from a single tertiary center were reviewed. RESULTS: During 2005-2018, 8327 appendectomies were performed and 57 ANENs were diagnosed (average age 31.7 ± 17 years; 70.2% women; 17.5% Arab ethnicity; and 22.8% < 18 years of age). The cohort was divided according to year of diagnosis (Period A 2005-2011; Period B 2012-2018). No differences were found in ANEN incidence (0.75% and 0.62%, respectively, p = 0.104), epidemiologic or pathologic characteristics between periods. In period B, pathology reports were more comprehensive and use of specific imaging and biochemical studies was more prevalent. Hemicolectomy rates and results were similar (8 in Period A, 7 in Period B, p = 0.925). All patients remained alive for the duration of follow-up. CONCLUSIONS: No temporal changes in epidemiological, clinical or pathological features of ANENs were noted. Although clinico-pathological evaluation was more detailed after 2011, there was no change in rates of hemicolectomy or disease prognosis.

Appendiceal tumor incidence and an in-depth look at appendiceal neuroendocrine neoplasm in a cohort of 8,162 appendectomies: Full dataset.

Data describing appendiceal tumor incidence and epidemiology is limited. We collated data from appendectomy pathology reports between 2005 and 2018 in our institution and examined patient epidemiological and appendectomy pathological features [1]. Overall, 8,328 appendectomies were performed at our institution over the pre-specified time period and 8,162 patients had sufficient epidemiological data to be included in the analysis. A total of 153 patients (1.9%) were diagnosed with appendiceal tumors, of which 57 (37.3%) were Appendiceal Neuroendocrine Neoplasm (ANEN), 35 (22.9%) were mucinous cystadenoma and 34 (22.2%) ovarian cancer metastases. We further examined the ANEN cases in order to characterize initial patient and tumor characteristics, to evaluate the performance of further investigations and interventions, and ultimately to study the behavior of these tumors over time.

VIRTUAL ORTHOPEDIC-REHABILITATION-METABOLIC COLLABORATION FOR TREATING OSTEOPOROTIC HIP FRACTURES.

Objective: To evaluate the effectiveness of a virtual, closed-loop protocol that treated hip fracture patients without formal clinic visits. Methods: In this prospective cohort study, an intervention group of 85 hip fracture patients (33.6%) with vitamin D levels ≥65 nmol/L who received recommendations for osteoporosis treatment, was compared to a nonintervention group of 168 (66.4%), with vitamin D <65 nmol/L. Treatment included vitamin D loading in orthopedic and rehabilitation departments for patients from both groups, and virtual, osteoporosis treatment recommendations by Metabolic Clinic physicians to patients from the intervention group upon achieving a vitamin D level ≥65 nmol/L. Recommendations were given without requiring clinic visits. Osteoporosis drug recommendations were relayed to primary care physicians. The primary endpoint was patients receiving osteoporosis drugs within 12-months post-surgery. Secondary endpoints were patients issued drugs within 3- and 6-months post-surgery, and 1-year post-fracture mortality rates. Results: Among 253 hip fracture patients (81.3 ± 10.7 years-of-age, 68.8% women), the postintervention osteoporosis medication issue rate was higher than in the nonintervention group (48.2% versus 22.0%, respectively; P<.001). More intervention group patients received drugs 3 months (18.8% versus 2.9%; P<.001) and 6 months after surgery (40% versus 5.9%; P<.001). One-year mortality was lower among patients who received any osteoporosis medications (either through our intervention or from community physicians) than among untreated patients (5.1% versus 26.3%; P<.001). Conclusion: Virtual orthopedic-rehabilitation-metabolic collaboration increased osteoporosis treatment rates post-hip fracture. Yet, treatment rates remained <50%. Additional research is required to increase treatment rates further, such as providing drug therapy shortly after surgery, perhaps during rehabilitation, or lowering the vita-min D threshold. Abbreviations: CHS = Clalit Health Services; FLS = Fracture liaison service; HMO = Health Maintenance Organization; MMC = Meir Medical Center; PCP = primary care physician.

Patients' knowledge and opinions regarding osteoporosis, osteoporosis treatment, and oral health care.

BACKGROUND: In this study, the authors assessed the knowledge and opinions of patients regarding osteoporosis and the associations among osteoporosis, osteoporosis treatments, and oral health care use. METHODS: Outpatients with osteopenia or osteoporosis completed a questionnaire, including sociodemographic data, internet use, osteoporosis status, oral health care use status, and knowledge regarding the effect of osteoporosis pharmacotherapy on dental procedures. RESULTS: Among 258 patients (mean [standard deviation] age, 68.5 [9.3] years; 93% female), 83.9% had osteoporosis, one-third had previous osteoporotic fracture, and 74.4% took osteoporosis medication, mostly antiresorptive agents. In addition, 66.3% had more than 12 years of education, and 53.9% used the internet daily. A total of 79.9% visited a dentist during the past year, and 29.0% had undergone an invasive procedure. Yet 46.5% estimated that their dentist did not know that they had osteoporosis. Approximately one-half of the participants responded that they did not know the answers to knowledge questions regarding associations between osteoporosis, its pharmacotherapy, and oral health care. Of the patients who answered questions about associations between osteoporosis and oral health care, 70% incorrectly believed osteoporosis increased gingival disease, and 30% incorrectly thought medications should be discontinued before caries restoration. CONCLUSIONS: Outpatients with osteoporosis or osteopenia who responded to a questionnaire had limited knowledge about associations among osteoporosis, osteoporotic treatment, and oral health care. PRACTICE IMPLICATIONS: Dentists should review previous and current medical treatments with their patients, including osteoporosis diagnoses. The medical community should make more efforts to provide balanced, accurate information to help patients prioritize health care treatment and avoid unnecessary interruptions in osteoporosis treatment.

Prevalence and clinical significance of hypercalcemia at diagnosis in diffuse large B-cell lymphoma.

The reported prevalence of hypercalcemia at diagnosis in non-Hodgkin-lymphoma ranges between 1.3% and 7.4%. These studies included all patients, regardless of lymphoma subtype. We performed a retrospective case-control study to determine the prevalence of hypercalcemia at time of diagnosis in patients with diffuse large B-cell lymphoma (DLBCL). Among 250 newly diagnosed patients, 46 (18%) had hypercalcemia. When compared with age-sex matched patients and normal calcium levels, those with hypercalcemia had higher levels of LDH, lower levels of albumin and more advanced stage. These differences were translated to shorter progression-free-survival and overall survival, but only in patients with hypercalcemia and low levels of parathyroid hormone (PTH). These findings suggest that in newly diagnosed patients with DLBCL, hypercalcemia is more frequent than previously appreciated. Furthermore, lymphoma-related but not primary hyperparathyroidism-related hypercalcemia is associated with adverse prognostic factors and adverse clinical outcomes in DLBCL. Hence, PTH should be obtained in patients with DLBCL and hypercalcemia at diagnosis.

A RETROPERITONEAL SEMINOMA WITH ENTRAPPED NERVE GANGLION MASQUERADING AS A PARAGANGLIOMA.

OBJECTIVE: The differential diagnosis of retroperito-neal tumors includes lymphoid, germ cell, and neurogenic tumors such as paraganglioma. Paragangliomas are rare neuroendocrine tumors of the autonomic nervous system, which may secrete catecholamines and their metabolites. Clinical features include sustained or paroxysmal hypertension, headaches, sweating, and palpitations. Here we present an unusual case of a retroperitoneal tumor entrapping a sympathetic nerve ganglion and mimicking paraganglioma. METHODS: A 57-year-old man with a history of controlled hypertension presented with paroxysms of tachycardia, flushing, high blood pressure, and headache. Ambulatory blood pressure monitoring showed uncontrolled labile hypertension with a normal nocturnal dip. Abdominal computed tomography (CT) demonstrated a 6.1 cm mass in the right retroperitoneum with adjacent lymphadenopathy. Paraganglioma was suspected and 24-hour urine demonstrated elevated normetanephrines (575 mcg/24 hours; normal, 5 to 290 mcg/24 hours) and vanillylmandelic acid (8.3 mg/24 hours; normal, 0.5 to 6.6 mg/24 hours). 68-Gallium DOTATATE positron emission tomography/CT showed weak uptake in the retroperitoneal mass and no other mass lesions. RESULTS: Following preparation with alpha-adrenergic blockers, surgical excision was performed with diagnostic and curative intent. Postoperatively, hypertension and paroxysmal symptoms resolved completely. The histopathology report described seminoma with an entrapped large ganglion within the tumor. CONCLUSION: We describe a retroperitoneal seminoma with an entrapped ganglion causing hypertension and paroxysmal symptoms, with laboratory and imaging features compatible with paraganglioma. Awareness of the rare possibility of mechanical pressure on a ganglion, within the differential diagnosis of retroperitoneal mass and sympathetic symptoms may aid in clinical decision making in atypical cases.

Orthopedic-Metabolic Collaborative Management for Osteoporotic Hip Fracture.

OBJECTIVE: Osteoporotic hip fractures are associated with increased morbidity, mortality, and secondary fractures. Although osteoporosis treatment can reduce future fracture risk, patients often do not receive it. We report results of a coordinator-less fracture liaison service in Israel addressing hip fracture patients. The primary endpoint was attending the Metabolic Clinic. Secondary endpoints included vitamin D measurement, calcium and vitamin D recommendations, initiation of osteoporosis treatment, and mortality 1-year post-fracture. METHODS: This prospective study included 219 hip fracture patients who were compared with historical controls. Data on hospitalized patients were collected before and after implementation of a structured protocol for hip fracture patients, led by a multidisciplinary team, without a coordinator. RESULTS: The study included 219 and 218 patients ≥60 years old who were operated on in 2013 and 2012, respectively. Metabolic Clinic visits increased from 6.4 to 40.2% after the intervention ( P<.001). Among 14 patients who attended the Clinic in 2012, 85.7% began osteoporosis therapy; among 88 who attended in 2013, 45.5% were treated at the first visit. Vitamin D measurements and calcium and vitamin D supplementation increased postintervention (0.5-80.1%, P<.001; 30.8-84.7%, P<.001, respectively). Patients receiving osteoporosis medications had lower mortality rates than untreated patients (4.3% vs. 21.8%). CONCLUSION: An Orthopedic-Metabolic team implemented by existing staff without a coordinator can improve osteoporosis care for hip fracture patients. Yet, gaps remain as only 40% had Metabolic Clinic follow-up postintervention, and of these, only half received specific treatment recommendations. Hospitals are encouraged to adopt secondary fracture prevention protocols and continuously improve them to close the gaps between current management and appropriate metabolic assessment and treatment. ABBREVIATIONS: CHS = Clalit Health Services; CI = confidence interval; FLS = fracture liaison service; HMO = health maintenance organization; OR = odds ratio.

Vertebral Fractures Following Denosumab Discontinuation in Patients with Prolonged Exposure to Bisphosphonates.

Denosumab (DMAB) efficacy for treatment of osteoporosis was demonstrated in a pivotal trial with a reduction in vertebral and hip fractures during 3 years, and fracture risk reduction was sustained up to 10 years in an extension study. DMAB causes potent yet reversible inhibition of bone resorption. Bone density declines rapidly upon discontinuation and bone turnover markers increase above baseline in a rebound fashion. Spontaneous multiple vertebral fractures after DMAB discontinuation were recently reported. Prior treatment with bisphosphonates (BP) was postulated to decrease the risk for this alarming phenomenon. We aimed to describe our experience of fractures following DMAB withdrawal with special attention to past history of osteoporosis treatment. A phone survey of physicians engaged in bone metabolism from nine hospitals in Israel was performed. Clinical data of the patients presenting with vertebral fractures upon DMAB discontinuation were summarized and compared to the previously published cases. Nine elderly (74.2 ± 5.3 years) female patients were identified. Most patients had a prolonged prior exposure to BP (7.4 ± 3.2 years). All but one sustained osteoporotic fractures prior to DMAB initiation and their FRAX scores were high. Thirty-six vertebral fractures were identified in nine patients. Eight patients presented with multiple fractures, and most fractures were spontaneous. In line with the previous reports, the timing and severity of the fractures raise concern of DMAB discontinuation effect. Prolonged BP exposure in most of our patients challenges the protective effect hypothesis. Care providers, patients, and regulatory authorities should be aware of the possible risk of DMAB treatment interruption.

Does parvovirus infection have a role in systemic lupus erythematosus?

We sought to evaluate a possible link between parvovirus B19 infection and the clinical and laboratory expression of systemic lupus erythematosus (SLE). SLE patients were examined to evaluate their clinical status and disease activity. A complete Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score was obtained for each patient. In addition, we determined the level of systemic involvement throughout the course of the disease. Blood levels of IgM and IgG antibodies to parvovirus B19, levels of anti-dsDNA, C3, and C4 were measured. A PCR real-time assay was used to determine the presence of parvovirus B19 genetic material. The viral genome was found in sera of 2 of 51(3.9%) patients with SLE. There was no correlation between viral serology and the clinical and serological parameters of the disease. More SLE patients with secondary antiphospholipid syndrome (APS) had IgG and IgM antibodies to the virus (p < 0.029 and p < 0.018, respectively). These patients also had a higher titer of IgG antibodies to parvovirus B19 compared to SLE patients without APS. In this group of SLE patients, no association was found between parvovirus infection and the presence or activity of SLE. The results of the study suggest an association between parvovirus infection and antibody production directed against phospholipids.

Classical and additional antiphospholipid antibodies in blood samples of ischemic stroke patients and healthy controls.

Classical antiphospholipid antibodies (aPLa) are found in 6-25% of blood samples from stroke patients. The frequency of novel aPLa antibodies in blood samples of CVA patients is not known. Enzyme-linked immunosorbent assays (ELISA) were performed on blood samples from 209 CVA patients (170 samples were obtained during the acute phase and 39 samples were from patients with complete carotid stenosis) and compared to 54 healthy controls. Subjects were tested for the presence of the classical aPL antibodies anticardiolipin (aCL) and anti-beta2-glycoprotein (aß2gI), in addition to antiphosphatidylethanolamine (aPE), anti-phosphatidylserine (aPS), and Annexin V. All antibodies were tested for both IgM and IgG subclasses. Numeric analysis of the antibody titer levels (µ/ml) revealed a significantly higher subclinical titer by two standard deviations of many aPL autoantibodies among CVA patients (Pv < 0.05). However, according to the kit manufacturer's cutoff value, no positive antibodies were found except a trend toward higher percentage of positive aPS IgG titer in the CVA group compared to controls (6.2 vs. %0; P = 0.077). According to the manufacturer's cutoff, significantly higher levels of positive antibodies were not found among stroke patients. However, the absolute ELISA values of stroke patients were significantly higher. These results suggest that lower cutoff values than those used for APS diagnosis should be used for risk stratification of CVA among healthy individuals.

Hepatitis B carrier state among SLE patients: case-control study.

The association between hepatitis B and autoimmune disorders has been intriguing for decades. Many reports have speculated on the possible linkage between these two conditions, yet never before data driven from a large national database was utilized in order to investigate this issue. The objective of this study was to investigate the association between SLE and hepatitis B carrier state. Patients with SLE were compared with age- and sex-matched controls regarding the proportion of hepatitis B carrier state in a case-control study. Chi-square and t tests were used for univariate analysis, and a logistic regression model was used for multivariate analysis. The study was performed utilizing the medical database of Clalit Health Services. The study included 5018 lupus patients over the age of 20 years and 25,090 age- and sex-frequency-matched controls without SLE. The proportion of hepatitis B carriers was higher in SLE patients as compared to controls (0.9 and 0.56 %, respectively; p < 0.001). A significant association was also observed among patients in lower socioeconomic status. In a multivariate logistic regression analysis, SLE was significantly associated with hepatitis B (OR = 1.828, 95 % CI = 1.291-2.590). Patients with SLE have a greater proportion of hepatitis B carrier state than matched controls.

Compliance, Persistence, and Preferences Regarding Osteoporosis Treatment During Active Therapy or Drug Holiday.

Osteoporosis treatments reduce the risk of fractures by 30%-50%, but adherence after 1 year is only about 50%. Drug holiday, a period with no active treatment, is part of routine management. The objective of this study was to determine compliance and persistence with osteoporosis therapy among postmenopausal women and to assess attitudes regarding treatment resumption among patients on drug holiday. This was a prospective observational study of patients followed at a dedicated metabolic bone clinic September 2013-February 2014. Compliance was assessed by medication possession ratio (MPR; number of doses dispensed relative to the number prescribed). Persistence was defined as continuation of treatment without a >30-day gap in prescription refills. Of 150 patients (70.1 ± 8.1 years), 57% were prescribed a medication: 64% oral, mostly bisphosphonates. MPR ≥ 80% was found in 80% and <50% in 12%; it was 100% for zoledronic acid and denosumab and 97%, 85%, 83%, and 70% for raloxifene, teriparatide, oral bisphosphonates, and strontium ranelate, respectively. Of 39 patients prescribed oral bisphosphonates, 77% persisted with treatment, and 89% took them as directed. Of 64 patients on a drug holiday, 59% expressed confidence in their physician's future treatment choice, whereas 19% expressed concerns about resuming treatment. Compliance among patients attending a dedicated bone clinic was higher than that reported in the literature. High persistence and compliance may be specific to patients followed in this type of setting. This study provides new information about attitudes of patients on a drug holiday. Most were not concerned about resuming treatment and did not have a preferred medication.

[OSTEOPOROSIS AND DIABETES - IN WHICH WAY ARE THEY RELATED?]

INTRODUCTION: Diabetes and osteoporosis are common diseases with growing prevalence in the aging population. Many recent studies have reported an association between diabetes mellitus and an increased osteoporotic fracture rate. Compared to control subjects, decreased bone mineral density has been observed in patients with type 1 diabetes mellitus, while those with type 2 diabetes display a unique skeletal phenotype of increased bone mineral density, but impaired architectural structure and mineral properties. Accumulation of advanced glycation end products changes collagen structure and suppression of bone turnover causes impairment of repair and adaptation mechanisms. These seem to be significant factors impairing bone strength. In addition, longer disease duration, disease complications, insulin use and increased falls, as well as the use of drugs like thiazolidinediones for treatment, are all reported risk factors for fractures among patients with diabetes. Conventional diagnostic tools, including DXA measurements and the fracture risk assessment (FRAX) tool, seem to underestimate fracture risk so that for every FRAX, the actual risk of fracture is higher in the diabetic patient. Despite the unique pathophysiology of bone disease in patients with diabetes, as far as we know, existing drug treatments for osteoporosis are as effective as in patients without diabetes. Therefore, physicians should be aware of the higher risk for osteoporotic fracture among patients with diabetes and treat them according to the clinical algorithms used for all patients.

Vitamin D Antibodies in Systemic Sclerosis Patients: Findings and Clinical Correlations.

BACKGROUND: Vitamin D is a pivotal factor in calcium homeostasis and exerts immunomodulatory effects. Hypovitamin D has been demonstrated in systemic sclerosis (SSc) patients and may be related to more severe disease of longer duration and with extensive skin involvement. OBJECTIVES: To seek anti-vitamin D antibodies in SSc patients, as found by previous research in patients with systemic lupus erythematosus (SLE). METHODS: The study included 54 SSc patients and 41 volunteers. Immunoglobulin (Ig) G and IgM autoantibody levels against 25(OH)D and 1,25(OH)D were obtained from patients and controls and were compared. SSc patients were assessed for autoantibody profile and disease severity. RESULTS: Vitamin D antibodies were present in 87% of SSc patients and 42% of controls. Higher levels of anti-25(OH)D IgM antibodies were detected in SSc patients compared to controls (0.48 ± 0.22 vs. 0.29 ± 0.29, respectively, P = 0.002); however, IgG levels were lower in the SSc patients. No such discriminative. effect was found regarding anti-1,25(OH)D antibodies between SSc and controls. No correlation was found between,vitamin D antibodies and other autoantibodies, disease severity, or target organ damage. CONCLUSIONS: To the best of our knowledge; this is the first study of these novel, anti-vitamin D antibodies in SSc patients and the first time a correlation between IgM 25(OH) vitamin D antibodies and scleroderma has been identified. Further research on the pathophysiological significance and therapeutic potential of vitamin D is required.