Changes in body composition in early breast cancer patients treated with aromatase inhibitors.

PURPOSE: The aim of the study was to analyze the modification of total and regional body composition in early breast cancer patients treated with aromatase inhibitors (AIs). METHODS: This is a prospective, single-center, observational, longitudinal study. Four-hundred and twenty-eight patients treated with adjuvant aromatase inhibitors were enrolled at the Medical Oncology and Breast Unit of Spedali Civili Hospital in Brescia from September 2014 to June 2022. Several body composition parameters including total and regional fat and lean body mass were investigated with dual-energy X-ray absorptiometry (DXA) scan at baseline and after 18 months of treatment with aromatase inhibitors. RESULTS: A significant increase in fat body mass (mean + 7.2%, 95% confidence interval [CI]: 5.5;8.9%) and a reduction in lean body mass (mean -3.1%, 95% CI -3.9; -2.4) were documented in this population. The changes in fat and lean body mass varied considerably according to different body districts ranging between + 3.2% to + 10.9% and from-1.3% to -3.9%, respectively. CONCLUSION: Aromatase inhibitor adjuvant therapy in early breast cancer is associated with changes in body composition, with a wide variability among different body districts, leading to a risk of sarcopenic obesity. Supervised physical exercise that focuses on single body parts that may display detrimental variations may be beneficial for AIs treated patients.

Cirugía de escoliosis en pacientes con mielomeningocele / Scoliosis surgery in patients with myelomeningocele

Resumen: Objetivo: Evaluar en forma retrospectiva los resultados obtenidos y las complicaciones presentadas en el tratamiento quirúrgico de pacientes con escoliosis neuropática secundaria a mielomeningocele. Material y métodos: Entre Julio de 1991 y Julio de 2018 fueron tratados quirúrgicamente 40 pacientes consecutivos con diagnóstico de escoliosis neuropática secundaria a mielomeningocele, a quienes se les realizó artrodesis vertebral. Resultados: El promedio de observación fue de 10 años (rango de 2-27 años). Fueron 19 pacientes masculinos y 21 femeninos, con un promedio de edad de 13 años. La magnitud promedio de la curva escoliótica fue de 90o en el prequirúrgico y de 43o en el último control. Corrección promedio de 52%. La magnitud promedio de la oblicuidad pélvica fue de 19o en el prequirúrgico y de 9o en el último control. Corrección promedio de 53%. La magnitud preoperativa del balance coronal fue de 28.4 mm, al último control fue de 17 mm. Corrección promedio de 40%. La magnitud promedio de la cifosis fue de 50o en el prequirúrgico y de 41o en el último control. Corrección promedio de 18%. El balance sagital prequirúrgico fue de 63.3 mm, al último control fue de 38.3 mm. Corrección promedio de 40%. Hubo 13 complicaciones (32.5%), la infección fue la complicación observada con mayor frecuencia. Conclusión: Los principales objetivos de la estabilización quirúrgica en pacientes con mielomeningocele son obtener una columna estable, balanceada y sin dolor. Sin embargo, el tratamiento quirúrgico de estos pacientes continúa siendo difícil y está asociado a un alto porcentaje de complicaciones.

Abstract: Objective: The aim of the study was to evaluate the outcomes and complications in patients with myelomeningocele who have undergone spinal fusion for neuromuscular scoliosis. Material and methods: Retrospective study of 40 consecutive patients with myelomeningocele with neuromuscular scoliosis who underwent spinal arthrodesis, treated at our center between July 1991 and July 2028. Results: Mean follow up was 10 years. There were 19 male and 21 females. The average age at operation was 13 years. The mean preoperative scoliosis curve was 90o. At last follow up, the mean scoliosis curve was 43o. Mean correction of 52%. The average of pelvic obliquity was 19o. At last follow up de obliquity was 9o. Mean correction of 53%. The mean preoperative coronal balance was 28.4 mm. At the last follow up it was 17 mm. Mean correction of 40%. The mean preoperative kyphosis was 50o. At the last follow up it was 41o. Mean correction of 18%. The mean preoperative sagittal balance was 63.3 mm. At the last follow up it was 38.3 mm. Mean correction of 40%. There were 13 complications (32.5%), with infection being the most frequently observed complication. Conclusions: The goals of the spinal surgery in patients with MMC are to obtain a stable, balanced and painless spinal fusion. Although the surgical treatment of these patients remains difficult, it is associated with high complication rate.

Surgical fixation of displaced midshaft clavicular fractures with precontoured plates in adolescents. / Tratamiento de fracturas mediodiafisarias de clavícula con placas precontorneadas en adolescentes.

BACKGROUND: The use of plate fixation to treat displaced midshaft clavicular fractures in adults reduces complications and residual shoulder disability. New features of the precontoured locking plates have been shown to reduce the need for hardware removal in adults. There is a lack of studies evaluating surgical fixation of displaced clavicular fractures with precontoured plates in adolescents. We evaluate outcomes and complications of adolescents with displaced midshaft clavicular fractures treated with precontoured locking plates. MATERIALS AND METHODS: 40 adolescents with displaced midshaft clavicular fractures were surgically treated from January 2010 to May 2017. Outcomes were evaluated using the Constant score, the 11- item version of the Disabilities of Arm, Shoulder and Hand (QuickDASH) questionnaires, and radiographs, and a visual analog scale. Return-to-sport rate, level achieved, and complications were recorded. RESULTS: Mean follow-up was 50 months (18 - 108 months). Constant, Quick-DASH, and visual analog scale scores were 95.6, 2.8 and 0.5 points, respectively. 100% of adolescents returned to sports at the same level they had before injury. Mean time to return was 69 days and 95% of patients were able to return before 12 weeks. Complication rate was 12.5%, 3 patients (7.5%) required hardware removal. CONCLUSIONS: Adolescents with displaced midshaft clavicular fractures treated with precontoured locking plates exhibited satisfactory outcomes and low complication rate. Compared to other reports, this study had lower rates, anatomic plates might reduce hardware-related complications.

[Scoliosis surgery in patients with myelomeningocele]. / Cirugía de escoliosis en pacientes con mielomeningocele.

OBJECTIVE: The aim of the study was to evaluate the outcomes and complications in patients with myelomeningocele who have undergone spinal fusion for neuromuscular scoliosis. MATERIAL AND METHODS: Retrospective study of 40 consecutive patients with myelomeningocele with neuromuscular scoliosis who underwent spinal arthrodesis, treated at our center between July 1991 and July 2028. RESULTS: Mean follow up was 10 years. There were 19 male and 21 females. The average age at operation was 13 years. The mean preoperative scoliosis curve was 90o. At last follow up, the mean scoliosis curve was 43o. Mean correction of 52%. The average of pelvic obliquity was 19o. At last follow up de obliquity was 9o. Mean correction of 53%. The mean preoperative coronal balance was 28.4 mm. At the last follow up it was 17 mm. Mean correction of 40%. The mean preoperative kyphosis was 50o. At the last follow up it was 41o. Mean correction of 18%. The mean preoperative sagittal balance was 63.3 mm. At the last follow up it was 38.3 mm. Mean correction of 40%. There were 13 complications (32.5%), with infection being the most frequently observed complication. CONCLUSIONS: The goals of the spinal surgery in patients with MMC are to obtain a stable, balanced and painless spinal fusion. Although the surgical treatment of these patients remains difficult, it is associated with high complication rate.

OBJETIVO: Evaluar en forma retrospectiva los resultados obtenidos y las complicaciones presentadas en el tratamiento quirúrgico de pacientes con escoliosis neuropática secundaria a mielomeningocele. MATERIAL Y MÉTODOS: Entre Julio de 1991 y Julio de 2018 fueron tratados quirúrgicamente 40 pacientes consecutivos con diagnóstico de escoliosis neuropática secundaria a mielomeningocele, a quienes se les realizó artrodesis vertebral. RESULTADOS: El promedio de observación fue de 10 años (rango de 2-27 años). Fueron 19 pacientes masculinos y 21 femeninos, con un promedio de edad de 13 años. La magnitud promedio de la curva escoliótica fue de 90o en el prequirúrgico y de 43o en el último control. Corrección promedio de 52%. La magnitud promedio de la oblicuidad pélvica fue de 19o en el prequirúrgico y de 9o en el último control. Corrección promedio de 53%. La magnitud preoperativa del balance coronal fue de 28.4 mm, al último control fue de 17 mm. Corrección promedio de 40%. La magnitud promedio de la cifosis fue de 50o en el prequirúrgico y de 41o en el último control. Corrección promedio de 18%. El balance sagital prequirúrgico fue de 63.3 mm, al último control fue de 38.3 mm. Corrección promedio de 40%. Hubo 13 complicaciones (32.5%), la infección fue la complicación observada con mayor frecuencia. CONCLUSIÓN: Los principales objetivos de la estabilización quirúrgica en pacientes con mielomeningocele son obtener una columna estable, balanceada y sin dolor. Sin embargo, el tratamiento quirúrgico de estos pacientes continúa siendo difícil y está asociado a un alto porcentaje de complicaciones.

Idiopathic retroperitoneal fibrosis: clinicopathologic features and differential diagnosis.

Idiopathic retroperitoneal fibrosis (IRF) is a rare disease often causing obstructive uropathy. We evaluated the clinicopathologic features of 24 patients with IRF to characterize the histopathology of the disease and to provide a framework for the differential diagnosis with other retroperitoneal fibrosing conditions. Retroperitoneal specimens were analyzed by light and electron microscopy and by immunohistochemistry. Most patients presented with abdominal/lumbar pain, constitutional symptoms, and high acute-phase reactants. Overall, 20 had ureteral involvement and 13 developed acute renal failure. The retroperitoneal tissue consisted of a fibrous component and a chronic inflammatory infiltrate with the former characterized by myofibroblasts within a type-I collagen matrix. The infiltrate displayed perivascular and diffuse patterns containing lymphocytes, macrophages, plasma cells, and eosinophils. The perivascular aggregates had a central core of CD20(+) cells and a mantle of CD3(+) cells in equal proportions. In the areas of diffuse infiltrate, CD3(+) cells outnumbered the CD20(+) cells. Most plasma cells were positive for the IgG4 isotype. Small vessel vasculitis was found in the specimens of 11 patients. Our study indicates that a sclerotic background with myofibroblasts associated with a diffuse and perivascular infiltrate mainly consisting of T and B lymphocytes may be a pathological hallmark of IRF.

Hyperferritinaemia without iron overload: pathogenic and therapeutic implications.

It is not unusual to meet increased levels of ferritinaemia in patients apparently healthy. Among other causes of hyperferritinaemia, recently was described the Hereditary Hyperferritinemia Cataract Syndrome, a genetic condition characterized by increased serum ferritin values without iron overload and bilateral nuclear cataract, both of early onset. It has been demonstrated that single or double point mutations or deletions in the stem-loop structure of the iron regulatory element (I.R.E.) located in the 5 untranslated regions of the ferritin L-subunit gene (19q13.1) are responsible for the upregulation of ferritin. This overexpression only for the L-chain gives rise to typical piles in several tissues. When this altered ferritin accumulates in lens it causes bilateral nuclear cataracts, that is the peculiar sign of this syndrome. It is essential to differentiate true iron overload from Hereditary Hyperferritinaemia Cataract Syndrome (H.H.C.S.), because these patients rapidly develop iron deficient anaemia when venosectioned. Here we describe a case report about a 40 years old healthy female blood donor who presented isolated hyperferritinaemia without iron overload, in the absence of concomitant pathologies. Anamnestic, biochemical, instrumental and clinical investigations led us to diagnose H.H.C.S., a pathology first described in 1995. From 1995 to date about 40 cases concerning patients showing the characteristics of this syndrome from Europe, USA, and Australia were described. Biochemical, genetical and clinical investigations led finally to understand every matter of this pathology, providing conclusive and exhaustive explanations.

Clinical, biochemical and molecular findings in a series of families with hereditary hyperferritinaemia-cataract syndrome.

Hereditary hyperferritinaemia-cataract syndrome (HHCS) is an autosomal dominant disease caused by mutations in the iron responsive element (IRE) of the l-ferritin gene. Despite the elucidation of the genetic basis, the overall clinical spectrum of HHCS has been less well studied as, to date, only individual case reports have been described. Therefore, we studied a total of 62 patients in 14 unrelated families, with nine different mutations. No relevant symptoms other than visual impairment were found to be associated with the syndrome. A marked phenotypic variability was observed, particularly with regard to ocular involvement (i.e. age range at which cataract was diagnosed in 16 subjects with the C39T: 6-40 years). Similarly, serum ferritin levels varied substantially also within subjects sharing the same mutation (i.e. range for the A40G: 700-2412 microg/l). We followed an HHCS newborn in whom well-defined lens opacities were not detectable either at birth or at 1 year. The lens ferritin content was analysed in two subjects who underwent cataract surgery at different ages, with different cataract morphology. Values were similar and about 1500-fold higher than in controls. These observations suggest that: (i) in HHCS the cataract is not necessarily congenital; (ii) in addition to the IRE genotype, other genetic or environmental factors may modulate the phenotype, especially the severity of the cataract.

Linkage to chromosome 1q in Greek families with juvenile hemochromatosis.

Hereditary hemochromatosis (HH) is a genetically heterogeneous disease. The HFE gene resides on chromosome 6 and its mutations account for the majority of HH cases in populations of northern European ancestry. Recently, two new types of hemochromatosis have been identified: Juvenile hemochromatosis (JH or HFE2), which maps to chromosome 1q21, and an adult form defined as HFE 3, which results from mutations of the TFR 2 gene, located at 7q22. We have performed a linkage study in five unrelated families of Greek origin with non-HFE hemochromatosis. Linkage at the chromosome 1q21 JH locus was detected in affected members with the use of polymorphic markers. Comparison of haplotypes between Greek and Italian JH patients revealed the presence of a common haplotype. However, the fact that many other haplotypes carrying the JH defect were observed in the two populations indicates that the respective mutations may have occurred in different genetic backgrounds. We suggest that hemochromatosis patients without HFE mutations should be evaluated for other possible types of hemochromatosis since hemochromatosis type 3 (HFE3) has a clinical appearance similar to HFE 1, and JH may have a late onset in some cases.

Haemochromatosis in patients with beta-thalassaemia trait.

Severe iron overload has been reported in patients with the beta-thalassaemia trait. Studies performed before the discovery of the haemochromatosis gene (HFE) have yielded conflicting results: some suggest that iron overload might arise from the interaction of the beta-thalassaemia trait with heterozygosity for haemochromatosis, some with homozygosity for haemochromatosis and others that it was unrelated to haemochromatosis. We have studied the clinical phenotype, iron indices and HFE genotypes of 22 unrelated patients with the beta-thalassaemia trait and haemochromatosis, the inheritance of chromosome 6p and 1q haplotypes in families of non-homozygous C282Y probands and serum measures of iron status in relatives heterozygous for C282Y with or without the beta-thalassaemia trait. We demonstrate that the beta-thalassaemia trait aggravates the clinical picture of C282Y homozygotes, favouring higher rates of iron accumulation and the development of severe iron-related complications. We suggest that the coexistence of the beta-thalassaemia trait might also increase the risk of iron overload in patients with HFE genotypes at a mild risk of haemochromatosis. Our findings do not support the hypothesis that the association of the beta-thalassaemia trait with a single C282Y or H63D allele might lead to iron overload and suggest that other non-HFE-related inherited factors are present in haemochromatosis patients with incomplete HFE genotypes.

Recurrent mutations in the iron regulatory element of L-ferritin in hereditary hyperferritinemia-cataract syndrome.

BACKGROUND AND OBJECTIVE: Hereditary hyperferritinemia-cataract syndrome (HHCS) is an autosomal dominant disorder characterized by bilateral cataracts and increased serum and tissue L-ferritin, in the absence of iron overload. The deregulation of ferritin production is caused by heterogeneous mutations in the iron regulatory element (IRE) of L-ferritin that interfere with the binding of iron regulatory proteins. DESIGN AND METHODS: We have identified several patients from three unrelated Italian families with HHCS. Iron parameters were assessed by standard methods. The IRE element of L-ferritin was amplified by PCR using appropriate primers and directly sequenced. RESULTS: Ferritin levels ranged from 918 microg/L to 2490 microg/L in the patients studied. In one family bilateral cataracts were diagnosed early in life, whereas in the others cataracts were diagnosed around 40-50 years. The female proband of family 3 presented with a severe iron deficiency anemia, which was unrecognized because of the increased ferritin values. Sequencing of the IRE element of L-ferritin in the probands of the three families identified three different nucleotide substitutions (+32 GAE A, +40 AAE G and +39 CT) in the IRE of L-ferritin. These mutations have already been reported in unrelated subjects of different ethnic origins. INTERPRETATION AND CONCLUSIONS: Our findings are consistent with recurrent mutations associated with HHCS and underline the importance of this syndrome in the differential diagnosis of unexplained hyperferritinemia. In addition, the findings highlight the role played by transferrin saturation in the diagnosis of iron deficiency in these patients.

Juvenile hemochromatosis locus maps to chromosome 1q.

Juvenile hemochromatosis (JH) is an autosomal recessive disorder that leads to severe iron loading in the 2d to 3d decade of life. Affected members in families with JH do not show linkage to chromosome 6p and do not have mutations in the HFE gene that lead to the common hereditary hemochromatosis. In this study we performed a genomewide search to map the JH locus in nine families: six consanguineous and three with multiple affected patients. This strategy allowed us to identify the JH locus on the long arm of chromosome 1. A maximum LOD score of 5.75 at a recombination fraction of 0 was detected with marker D1S498, and a LOD score of 5. 16 at a recombination fraction of 0 was detected for marker D1S2344. Homozygosity mapping in consanguineous families defined the limits of the candidate region in an approximately 4-cM interval between markers D1S442 and D1S2347. Analysis of genes mapped in this interval excluded obvious candidates. The JH locus does not correspond to the chromosomal localization of any known gene involved in iron metabolism. These findings provide a means to recognize, at an early age, patients in affected families. They also provide a starting point for the identification of the affected gene by positional cloning.

Inherited HFE-unrelated hemochromatosis in Italian families.

Hemochromatosis (HH) is usually caused by the homozygous state for C282Y mutation in the HFE gene. A minority of iron loaded patients have no mutations in this gene. An infrequent subset shows an early-onset aggressive disorder, denoted juvenile hemochromatosis (JH), which has no linkage to 6p. In this report we describe six patients from three unrelated Italian families, four men and two women, aged 21 to 44 with the typical hemochromatosis phenotype, who are homozygous for the wild type allele at the HFE gene. In two families the disorder is unlinked to 6p; in one family some features of the juvenile form are seen, but linkage to 6p is not excluded. Our results point to genetic forms of hemochromatosis not associated with HFE and raise the problem of whether non-HFE hemochromatosis in Italy is related to the "juvenile" form. They also emphasize the importance of phenotypic as well as genetic diagnosis of HH.

Studies on the oxygen transport in the clinical association between Hb-S and Hb-C.

The whole blood oxygen affinity of a Negro carrier of SC disease was found to be characterized by some right-shifted p50 and clearly increased Bohr effect, whereas the isolated and purified Hb-S and Hb-C exhibited slight deficiencies mainly of the Bohr effect. The right-shifted p50 from whole blood can be easily explained by the mild anemia with a parallel increase of 2,3-diphosphoglycerate (DPG), whereas the functional discrepancies between whole blood function and that of the purified Hb-S and C could be due, at least in part, to the presence in vivo of consistent amounts of hybrid Hb tetramers of the type alpha alpha beta S beta C. Unfortunately, the mechanism promoting the formation (or dissolution) of hybrids are fundamentally unknown; so, either their presence and functional properties are very difficult to be explored.

A recombination event close to HFE gene in hereditary hemochromatosis.

A candidate gene for Hereditary Hemochromatosis (HFE) has been recently cloned from a region 4 cM telomeric to HLA-A on the short arm of chromosome 6. This gene, defined HFE, is mutated in a high proportion of HFE patients. Positional cloning of HFE has been difficult, because of the extended region of linkage disequilibrium observed around the gene and of the rarity of recombination events in this DNA area. Here we describe a crossover in an Italian HFE patient which occurred close to the HFE gene in a restricted interval between D6S2221 and D6S2240-D6S2238 markers. The molecular analysis of this event and the segregation of the HFE mutations in the family are consistent with the position of the HFE gene telomeric to D6S2221.

Juvenile and adult hemochromatosis are distinct genetic disorders.

Juvenile Hemochromatosis (JH) is a rare genetic disorder that causes iron overload. JH clinical features are similar to those of hemochromatosis (HFE), but the clinical course is more severe and is characterized by an earlier onset and by a prevalence of cardiac symptoms and endocrine dysfunctions. Here we describe seven Italian patients belonging to five unrelated families with clinical features typical of JH. In four out of five families the parents were consanguineous. Analysis of HFE gene mutations in all the cases and nucleotide sequence of the gene in one case excluded this gene as responsible for JH. Segregation analysis of 6p markers closely associated with HFE in families with consanguineous parents clearly showed that JH is unlinked to 6p and thus genetically distinct from HFE.

Symptomatic treatment of osteoarthrosis with two different oral preparations of naproxen.

A new oral Naproxen retard preparation (750 mg once daily) was compared with a standard commercial formula (375 mg BID) in a population of 60 patients affected by osteoarthritis or rheumatoid arthritis. An assessment was made of the effects on the clinical parameters, inflammation indexes (ESR, PCR, urinary hydroxyproline) and general tolerance parameters after one month of treatment. Once the steady state had been reached, no significant differences were observed even 24 h after the administration of a single 750 mg dose of Naproxen retard as compared with the administration of two 375 mg doses of standard Naproxen taken every 12 hours. Both treatments induced a similar improvement in the clinical and laboratory parameters and were shown to be equally safe. However, tolerance at a gastro-enteric level was, better with the retard preparation.