Tumor induced osteomalacia: A single center experience on 17 patients.

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome due to a phosphaturic tumor, which overproduces Fibroblast Growth Factor 23 (FGF-23), causing hyperphosphaturia, hypophosphatemia, low 1,25(OH)2D and osteomalacia. Tumor localization is critical, diagnostic delay ranges from 2.5 to 28 years and to date surgical removal is considered effective treatment. We retrospectively evaluated patients with definite diagnosis of TIO referred to a tertiary Rheumatology Center between September 2000 and May 2020, investigating clinical management and disease outcome. We included 17 patients: 10 (58.8%) were females, mean age at diagnosis was 55.3 ± 13.9 years (mean ± standard deviation), with a diagnostic delay from symptoms onset to tumor detection of 6.6 ± 6.25 years. Biochemical data were: serum phosphorus 1.3 ± 0.4 mg/dL (Reference Range: 2.5-4.6), serum 1,25(OH)2D 31.8 ± 22.9 ng/mL (RR: 25-86), intact FGF-23, 358.9 ± 677 pg/mL (RR: 25-45); 24 h-Urine Phosphorus was increased in only 2 patients, while tubular reabsorption of phosphate (TRP) was decreased in all patients confirming a renal phosphate wasting. In 2013 68Ga- DOTA-based PET/CT was introduced in routinely practice and diagnostic delay was consistently reduced (from 8.6 ± 7.9 to 4.3 ± 2.4 years). Thirteen patients underwent surgery, one patient underwent radiofrequency ablation; 3 patients, not eligible for surgery, were treated only with supplements of phosphorus and calcitriol. One was started on Burosumab after several unsuccessful surgical attempts. After surgery or ablation, 8 patients had complete remission, 3 TIO persistence, and 3 had overtime relapse. Relapses were observed only in patients who previously underwent closed biopsy. To our knowledge, this is the widest European cohort of TIO patients in the last two decades. We confirm a usual diagnostic delay and recommend a stepwise diagnostic approach. Tumor biopsy is not recommended due to the potential cell spilling. Surgery is generally considered a definitive treatment, even though other approaches have been successful in curing TIO. Active surveillance on possible recurrence is always needed. Burosumab appears a promising therapy.

Emotive and cognitive processes in cancer patients: linguistic profiles of post-traumatic growth.

Starting from the challenge offered by the authors of the post-traumatic growth (PTG) construct (Tedeschi & Calhoun, ), this paper aims to explore the existence of different linguistic profiles of cognitive and emotional processes in PTG narratives. The autobiographical narratives of 40 cancer patients were analysed for both PTG and linguistic indicators of emotions and cognitive processes. PTG was operationalised as the presence of redemption sequences (McAdams, ). The emotional and cognitive linguistic indicators were analysed by the LIWC program (Pennebaker & Francis, ). All the narratives included PTG (M = 3.55, SD = 1.91). Three clusters of linguistic profiles were retained (60%-79% of variance explained): "disengagement", "assimilative" and "accommodative". These clusters differed significantly by PTG (F = 9.70, p < .000, η2  = .34). Given the limitations of the study, the results highlight the importance of the linguistic approach to a deeper understanding of PTG and to tailored pathways of its promotion.

Increased Bone Resorption: A Possible Pathophysiological Link Between Hypovitaminosis D and Peripheral Arterial Disease.

OBJECTIVE/BACKGROUND: Vitamin D deficiency has been associated with the prevalence and severity of peripheral arterial disease (PAD); nevertheless, data on bone turnover in patients with PAD is lacking. The present study investigates a possible relationship between the markers of bone turnover and the presence and severity of PAD. METHODS: The study examined 143 patients, with a mean ± SD age of 75.3 ± 8.5 years (range 50.0-93.0 years), of both sexes, admitted to a department of internal medicine. All patients underwent ankle brachial index (ABI) assessment by Doppler velocimetry. Serum levels of 25(OH) vitamin D and two markers of bone turnover, C-terminal telopeptide of type I collagen (sCTX) and bone isoenzyme of alkaline phosphatase, were measured. The differences between patients with normal ABI and patients with PAD were analyzed. Pearson and Spearman correlation coefficients were calculated and independent predictors were identified through a stepwise linear regression analysis. Odds ratios were calculated with a logistic regression model. RESULTS: Compared with patients with a normal ABI (≥0.90), patients with PAD (ABI < 0.90) presented with significantly lower levels of 25(OH) vitamin D (12.2 ± 9.6 ng/mL vs. 16.7 ± 8.7 ng/mL; p = .006) and a significantly higher concentration of sCTX (1.1 ± 0.7 ng/mL vs. 0.6 ± 0.4 ng/mL; p < .001). There was a positive correlation between ABI and serum concentration of 25 (OH) vitamin D (r = 0.3; p < .001), whereas ABI was inversely correlated with the concentration of sCTX (r = -0.358; p < .001). At logistic regression analysis, age, cigarette smoking, and both vitamin D and sCTX were independent predictors of an ABI < 0.90. CONCLUSION: These results support the hypothesis that hypovitaminosis D and increased bone turnover are risk factors for the presence and severity of PAD. Furthermore, the presence of PAD, even if asymptomatic and diagnosed by a reduced ABI, could identify a population at risk for osteoporosis and osteomalacia.

Bioelectrical impedance vector analysis (BIVA) for the assessment of two-compartment body composition.

This review is directed to define the efficacy of bioelectrical impedance vector analysis (BIVA) for assessing two-compartment body composition. A systematic literature review using MEDLINE database up to 12 February 2014 was performed. The list of papers citing the first description of BIVA, obtained from SCOPUS, and the reference lists of included studies were also searched. Selection criteria included studies comparing the results of BIVA with those of other techniques, and studies analyzing bioelectrical vectors of obese, athletic, cachectic and lean individuals. Thirty articles met the inclusion criteria. The ability of classic BIVA for assessing two-compartment body composition has been mainly evaluated by means of indirect techniques, such as anthropometry and bioelectrical impedance analysis (BIA). Classic BIVA showed a high agreement with body mass index, that can be interpreted in relation to the greater body mass of obese and athletic individuals, whereas the comparison with BIA showed less consistent results, especially in diseased individuals. When a reference method was used, classic BIVA failed to accurately recognize FM% variations, whereas specific BIVA furnished good results. Specific BIVA is a promising alternative to classic BIVA for assessing two-compartment body composition, with potential application in nutritional, sport and geriatric medicine.

Is fibromyalgia a cause of failure in the treatment of a painful shoulder?

PURPOSE: This study aims to review the incidence of fibromyalgia in a cohort of patients who were treated for shoulder pain and address whether a concomitant fibromyalgia could have had detrimental effect on outcomes. METHODS: The treatment of 286 consecutive patients for shoulder pain was reviewed. RESULTS: Eighteen patients (6.3 %) were diagnosed as having fibromyalgia, but in 13 of them (72 %), the diagnosis was initially missed. Five patients received a total of 11 surgeries for treatment of the shoulder. At an average follow-up of 15 months (range 12-27), the average new Oxford shoulder score (OS score) was 49 % (range 6-87 %). The average physical component of the Short-Form-12 Healthy Survey (SF-12) was 36 (range 21-55), and the mental component 30 (range 15-46). The Summary Outcome Determination score (SOD score) was 1.3 (range-3 to 6). CONCLUSIONS: Fibromyalgia occurs relatively frequently in patients who complain of shoulder pain and it can be a cause of failure in the treatment of concomitant painful shoulder conditions.

Anti-inflammatory effect of 3,4-DHPEA-EDA [2-(3,4 -hydroxyphenyl) ethyl (3S, 4E)-4-formyl-3-(2-oxoethyl)hex-4-enoate] on primary human vascular endothelial cells.

Diets in which fat is significantly provided by olive oil and are relatively rich in vegetables, have been associated with a low incidence of cardiovascular diseases, mostly due to the presence of several phenolic compounds which have anti-oxidant and antiinflammatory properties. [1]. In this work, we describe the anti-inflammatory effect of 3,4-DHPEA-EDA in a cell model that we developed to mimic inflammatory injury of endothelium. This was based on the production of the proinflammatory chemokine CCL2, following in vitro stimulation of primary human endothelial cells. Pre-treatment of cells with 3,4-DHPEA-EDA resulted in a dose-dependent inhibition of CCL2 secretion. The effect of 3,4-DHPEA-EDA on CCL2 expression was observed at the transcriptional level. Functional data have shown that 3,4-DHPEA-EDA diminished monocyte adhesion to HUVECs. These results point on the use of 3,4- DHPEA-EDA as a novel drug aimed to prevent or reduce inflammation of endothelium.

Small (

PURPOSE: We prospectively compared gadoliniumenhanced magnetic resonance imaging (dynamic MRI), superparamagnetic iron oxide (SPIO) (ferucarbotran) MRI and multidetector-row computed tomography (MDCT) and the combination of dynamic MRI plus MDCT vs. dynamic MRI plus SPIO-MRI (double-contrast MRI: DC-MRI) for the detection of small (1 cm and the highest specificity (83.3%) superior to dynamic MRI (p<0.0001). In the per-lesion analysis, SPIO-MRI demonstrated a positive predictive value higher than dynamic MRI (p=0.0059) and than both the combinations dynamic MRI/MDCT and DC-MRI (p=0.0021 and p=0.0087, respectively). DC-MRI showed the highest sensitivity (97.7%) and accuracy (78.9%), detecting hypovascular and atypical HCCs >1 cm. Furthermore its per-patient negative predictive value was the highest (100%), and significantly higher than all the other methods. CONCLUSIONS: DC-MRI is the most sensitive and accurate method and can be confidently used as a single-step procedure for the detection of small HCCs, with the exception of lesions <1 cm.

Pain relief and motor function during continuous interscalene analgesia after open shoulder surgery: a prospective, randomized, double-blind comparison between levobupivacaine 0.25%, and ropivacaine 0.25% or 0.4%.

BACKGROUND AND OBJECTIVES: To compare pain relief and motor impairment of 0.25% levobupivacaine with either an equivalent (0.25%) or equipotent (0.4%) concentration of ropivacaine for continuous interscalene block after open shoulder surgery. METHODS: Seventy-two adult patients scheduled for elective major shoulder surgery received an interscalene injection of mepivacaine 1.5% 30 mL followed by 24 h patient-controlled interscalene analgesia (basal infusion rate: 5 mL h-1; incremental bolus: 2 mL; lockout period: 10 min; maximum boluses per hour: 4) with either 0.25% levobupivacaine (n = 24), 0.25% ropivacaine (n = 24) or 0.4% ropivacaine (n = 24). A blinded observer recorded the evolution of pain relief and recovery of motor block during the first 24 h. Motor function was assessed as the maximum pressure developed while squeezing a sphygmomanometer cuff with the blocked hand. The reduction from preoperative values was considered as an index of motor impairment. RESULTS: No differences were reported among the three groups in the quality of postoperative analgesia. The number of incremental patient-controlled interscalene analgesia doses, total volume of local anaesthetic infused during the 24-h patient-controlled interscalene analgesia, and number of rescue ketoprofen analgesia were higher in the ropivacaine 0.25% group than in the other two groups (P = 0.0005). The hand strength recovered to >or=90% of baseline values within the first 24 h of infusion in all groups, without differences among the three groups. CONCLUSION: When providing patient-controlled interscalene analgesia after open shoulder surgery 0.25% levobupivacaine and 0.4% ropivacaine performed equally in terms of pain relief, motor block and number of patient-controlled boluses required, while patients receiving 0.25% ropivacaine needed significantly more boluses and rescue analgesia to control their pain.

Corticotrophin-releasing activity of desmopressin in Cushing's disease: lack of correlation between in vivo and in vitro responsiveness.

Desmopressin (DDAVP), an arginine vasopressin analogue, markedly stimulates ACTH secretion in patients with Cushing's disease, in contrast to its minimal effect in normal subjects. However, little is known about the mechanisms underlying this action and it appeared to be of interest to evaluate the effect of DDAVP on ACTH-secreting pituitary adenomas in vitro, in comparison with its effect in the same patients in vivo. Pituitary adenomas from 14 patients with Cushing's disease were incubated with DDAVP, corticotrophin-releasing hormone (CRH) and DDAVP together with vasopressin receptor antagonists or CRH. Incubation with DDAVP induced a modest dose-dependent increase in ACTH concentrations which appeared maximal at 10 nM. CRH stimulated ACTH to a greater extent compared with DDAVP and potentiated the effect of DDAVP alone. The DDAVP-induced ACTH increase appeared blunted by vasopressin V(2) and V(3) receptor antagonists. V(3) receptor gene expression was detected by RT-PCR in all adenoma samples except for two which were not responsive to DDAVP in vitro but responsive to the peptide in vivo. Surprisingly, no difference in the in vitro ACTH secretory response was observed between in vivo DDAVP-responsive (ACTH peak>150% baseline) and -unresponsive (ACTH peak<120% baseline) patients, suggesting that the pituitary adenoma is not the sole mediator of the ACTH-releasing effect of DDAVP. In conclusion, the marked stimulatory effect of DDAVP observed in patients with Cushing's disease appears to be mainly dependent on an extrapituitary action, possibly the inhibition of a corticotrophin release-inhibitory factor.

Polycyclic aromatic hydrocarbons air levels in Florence, Italy, and their correlation with other air pollutants.

Benzo(a)pyrene [B(a)P] air levels were measured in Florence (Italy) in the period 1992-2001. For the period 1999-2000 seven polycyclic aromatic hydrocarbons (PAH) (benzo(a)anthracene, crysene, benzo(a)pyrene (B(a)P), benzo(b)fluoranthene (B(b)F), benzo(k)fluoranthene, dibenzo(a,h)anthracene (DBA) and benzo(g,h,i)perylene (BGP)), were measured in the air in four different sites (one with heavy traffic (A), one in a park (B), one in a residential area (C) and one in a hill area (D)). B(a)P levels were elevated in 1992-1998 (maximum average value of winter months: 5.8 ng/ m3) but a decreasing trend was observed in the following years, probably due to improvement in vehicle emissions. The sum of PAH in the air in the period 1999-2000 was about one order of magnitude lower in the hill site (D) relative to the urban sites, and residential areas (B and C) had values 2.5-3 times lower compared to site A with a heavy traffic. PAH concentrations decreased in the warmer seasons of 2000 in all sites. A negative correlation was found between PAH levels and ozone. A positive correlation with carbon monoxide (CO) (r = 0.862, P < 0.001) and low B(a)P/BGP ratios, ranging from 0.44 to 0.51, indicated that vehicular traffic was the major PAH source in all monitored sites. Using B(a)P(TEF) values (toxic equivalency factors) for evaluating the biological activity of PAH, we found that the highest PAH contributors in terms of potential air carcinogenic activity were B(a)P and DBA. Therefore, in addition to B(a)P, DBA concentration should be considered in the evaluation of air quality in terms of PAH contamination.

Blood pressure rhythm and prevalence of vascular events in hypertensive subjects.

OBJECTIVES: To evaluate the influence of age on the day-night blood pressure rhythm and on the prevalence of vascular events in those whose systolic blood pressure (SBP) fell by <10% overnight (non-dippers). DESIGN: Cross-sectional observational cohort study. SETTING: Outpatient hypertension clinic. PARTICIPANTS: 419 Hypertensive patients (214 male, 205 female). METHODS: All subjects were submitted to ambulatory blood pressure monitoring (Spacelabs 90207). The nocturnal fall of SBP was calculated from (day SBP--night SBP)/day SBP, where 'day' values were recorded between 0600 h and 2200 h and 'night' values between 2200 h and 0600 h. Dippers and non-dippers were divided in two subgroups according to age (under or over 65 years). Information on gender, smoking, diabetes mellitus and body mass index was collected and cerebrovascular and cardiovascular events, evaluated by history and medical records, were registered. RESULTS: The day-night difference in blood pressure significantly decreased with age and the prevalence of non-dippers was greater in elderly than in younger subjects (65.1% vs. 29.8%). No difference was found between groups for cerebrovascular events, irrespective of age. A relationship between non-dipping pattern and cardiovascular events was found only in younger hypertensive non-dippers (odds ratio, 2.0; 95% confidence interval, 1.20-3.21); in elderly people the prevalence of cardiovascular events was similar in dippers and non-dippers. CONCLUSIONS: Cardiovascular risk is not increased in elderly non-dipper hypertensive subjects. This contrasts with results in younger populations.

[Carcinogens in the urban environment of Italian cities: benzene and benzo(a)pyrenes]. / Cancerogeni nell'ambiente urbano delle città italiane: benzene e benzo(a)pirene.

In Italian urban areas air pollution from benzene and benzo(a)pyrene-B(a)P--is mostly caused by traffic. The concentration limits in the atmosphere fixed by Italian legislation up to December 31, 1998 expressed as annual means are 15 micrograms/m3 and 2.5 ng/m3 for benzene and B(a)P respectively and, starting from January 1, 1999, 10 micrograms/m3 and 1 ng/m3. In the city of Florence the concentrations detected and expressed as annual means of benzene and B(a)P in an area with heavy traffic (32.1 micrograms/m3 and 3.5 ng/m3), in a densely populated area (9.2 micrograms/m3 and 1.86 ng/m3), and in a city park (6.0 micrograms/m3 and 0.25 ng/m3), suggest a marked progressive reduction in the atmospheric levels of these chemicals with the distance from the main roads. The environmental data obtained from densely populated areas of a number of Italian cities (Firenze, Milano, Roma, Bologna, Bolzano, Pavia, Modena), the only ones that allow evaluation of the health risk, show benzene concentrations ranging from 6.0 to 11.3 micrograms/m3 and B(a)P levels, measured in heavy traffic areas, from 1.0 to 3.5 ng/m3 respectively (annual mean in 1996). The data obtained in the city of Florence show that the population is exposed weekly to average concentrations of 14.3 micrograms/m3 for benzene and 2.0 ng/m3 for B(a)P. These results suggest that, regarding benzene and B(a)P pollution, the situation in Florence is far from being critical but not such as to ensure that long-term exposure is without adverse effects.

Long-term results of hydroxyapatite-fibrin glue implantation in plastic and reconstructive craniofacial surgery.

The bone tissue formed in orthotopic or heterotopic implants of granular, porous hydroxyapatite and fibrin glue was examined several (2 1/2-8) years after implantation. The results showed distinct ossification in all cases and the functional situation and external appearance were also satisfactory. The reconstituted spongy and compact bone underwent a remodelling process similar to that of normal bone. Most of the hydroxyapatite granules were embedded in the bone tissue; a few were very close to the fibrillar connective tissue of the intertrabecular spaces and were either covered by osteoid-like collagenous borders or were in contact with osteoclast-like giant cells. Even if the results refer only to a few patients, and were obtained from a cross-sectional study, they allow the conclusion to be reached that the implantation of porous hydroxyapatite and fibrin glue leads to the formation of long-lasting bone whose hardness is equal to, or greater than, that of normal bone.

Osteogenic response to hydroxyapatite-fibrin implants in maxillofacial bone defects.

Bone formation in hydroxyapatite-fibrin implants has been reported several times. However, available studies refer to experimental animals, or are limited to short periods after implantation. We report the results of histological, histochemical and ultrastructural studies carried out 2.5-8 yr after implantation of non-resorbable, porous hydroxyapatite (HA) and fibrin glue in human maxillofacial bones. Prominent ossification was found in all cases, with the presence of normally structured spongy bone. HA granules were embedded in the calcified bone matrix. They had not elicited inflammatory reactions and did not induce bone resorption. Ossification was preceded by the appearance of alkaline phosphatase activity on fibroblast-like cells, and by the formation of dense collagenous layers, similar to osteoid borders, on the surface of HA granules. The early phases of the calcification process occurred in these borders, with the appearance of calcification nodules adjacent to alkaline phosphatase-positive osteoblast-like cells. A remodeling process similar to that occurring in normal bones was found in the newly formed bone. These results justify the conclusion that HA-fibrin implants lead to the formation of long-lasting bone that does not differ from that of the normal maxillofacial skeleton. Mixing the HA granules with fibrin has the advantage of creating an easily mouldable material which can be adapted to any skeletal surface and stays in place after surgery.

Estudio multicentrico de prevalencia de infeccion por Helicobacter pylori en pacientes con patologia gastroduodenal cronica: algunos aspectos epidemiologicos / Multicenter study of Helicobacter pylori infection prevalence in patients with chronic gastroduodenal disease: some epidemiologic features

El objetivo de este trabajo fue establecer la prevalencia de infección por H. Pylori en pacientes con patología gastroduodenal crónica, atendidos en las unidades de gastroenterología de cuatro hospitales de Capital Federal y conurbano. Se estudiaron 398 pacientes con evaluación clínica y datos epidemiológicos, se efectuó endoscopía alta con toma de dos biopsias de antro gástrico para test rápido con ureasa y evaluación histológica, con coloración de giemsa, del estado de infección con H. Pylori. La prevalencia de infección en la población total estudiada fue de 75,6 por ciento. En los pacientes con úlcera gástrica la tasa de prevalencia de infección por H.P. fue 70 por ciento en úlcera duodenal 77,2 por ciento y en gastritis crónica fue 78,5 por ciento. La prevalencia de infección por H.P. en la población según grupos etarios para pacientes menores de 20 años fue 61,54 por ciento; entre 21 y 40 años: 80,39 por ciento; entre 41 y 60 años 76,41 por ciento y en mayores de 60 años fue 68,22 por ciento. se ha intentado obtener de una correlación entre prevalencia de la infección y algunas características sanitarias (agua corriente y cloacas) de la población estudiada. Se observó ue 225 pacientes que residen en viviendas con agua corriente y cloacas, tuvieron una prevalencia de infección de 69,345 y en 129 pacientes sin agua corriente ni cloacas se observó una tasa de prevalencia de infección de 83,72 por ciento una diferencia estadísticamente significativa con un p< 0,01 para los pacientes con pobres condicones sanitarias. Estos datos puedem ser importantes cuando se efectua el diseño de los esquemas terapéuticos de erradicación de la bacteria.

Palliative treatment of carcinoma of the rectum by endoscopic injection of polidocanol.

Between January 1987 and December 1988, at the Surgical Department of Chiarenzi Hospital, five patients underwent endoscopic intratumoral injection of polidocanol for palliative treatment of inoperable carcinoma of the rectum. Histological evaluation was performed in all cases. The patients comprised two males and three females aged 78 to 88 years (mean 83.4). One of them refused surgery for recurrent rectal cancer, four consulted us with impending intestinal obstruction; three were inoperable due to local spread of the tumor and poor general condition, the other was in a poor general condition due to massive metastatic hepatic disease. In all the patients, we observed remission of the obstructive symptoms with no major complications; none of them has required a colostomy. The follow-up period has covered a period of two months to two years. The technique of injection is simple, inexpensive and, properly performed, safe. All these advantages make this type of palliative treatment for rectal cancer interesting, even when compared with laser treatment, urological resectoscope or electric snare resection, and electrocoagulation.