Global risk stratification in primary hypertension: the role of the kidney

OBJECTIVE: Microalbuminuria and a reduction in creatinine clearance are well known, independent predictors of unfavourable cardiovascular prognosis. Our aim was to evaluate the impact of renal damage on global risk stratification in 459 non-diabetic, untreated hypertensive patients (64% men, mean age 47.3 years). METHODS: Renal damage was defined as creatinine clearance < 60 ml/min per 1.73 m2 (Cockcroft-Gault formula) or the presence of microalbuminuria (albumin to creatinine ratio). Cardiac and vascular organ damage was assessed by ultrasound scan. We evaluated the impact of renal damage, left ventricular hypertrophy and carotid atherosclerosis on risk stratification as recommended by the 2007 European Society of Hypertension-European Society of Cardiology Guidelines. RESULTS: The prevalence of renal damage, microalbuminuria and creatinine clearance < 60 ml/min per 1.73 m2 was 24, 12 and 13%, respectively. There was no correlation between albuminuria and estimated creatinine clearance, and only 0.9% of patients showed microalbuminuria and reduced creatinine clearance simultaneously. The presence of renal damage entailed a 3.3 times higher risk of having cardiovascular abnormalities. Based on routine work-up, 58% of our study patients were classified as high-very high risk. The simultaneous evaluation of albuminuria and creatinine clearance resulted in a significant change in risk stratification, since 68% of patients were classified in the high-very high risk class. The search for left ventricular hypertrophy or carotid atherosclerosis by ultrasonography did not improve risk stratification significantly as compared to the assessment of renal damage. CONCLUSIONS: Our findings support the assessment of renal abnormalities as the first step when evaluating target organ damage for cardiovascular risk assessment in hypertensive patients.     

A perioperative multidisciplinary care bundle reduces surgical site infections in patients undergoing synchronous colorectal and liver resection

Background

Surgical site infections (SSIs) are a major cause of morbidity, mortality, and healthcare costs, and patients undergoing simultaneous colorectal/liver resections are at an especially high SSI risk.

Physical exercise and vascular endothelial growth factor (VEGF) in elderly: A systematic review

The aim of this study was to conduct a systematic review of studies that verified the effects of physical exercise on vascular endothelial growth factor (VEGF) in elderly.     

A 20-year long term experience of the Italian Diamond-Blackfan Anaemia Registry: RPS and RPL genes,different faces of the same disease?

Diamond–Blackfan anaemia (DBA) is a rare and heterogeneous disease characterised by hypoplastic anaemia, congenital anomalies and a predisposition for malignancies. The aim of this paper is to report the findings from the Italian DBA Registry, and to discuss the Registry’s future challenges in tackling this disease. Our 20-year long work allowed the connection of 50 Italian Association of Paediatric Haematology and Oncology (AIEOP) centres and the recruitment of 283 cases. Almost all patients have been characterised at a molecular level (96%, 271/283), finding a causative mutation in 68% (184/271). We confirm the importance of determination of erythrocyte adenosine deaminase activity (eADA) and of ribosomal RNA assay in the diagnostic pipeline and characterisation of a remission state. Patients with mutations in large ribosomal subunit protein (RPL) genes had a significant correlation with the incidence of malformations, higher eADA levels and more severe outcomes, compared to patients with mutations in small ribosomal subunit protein (RPS) genes. Furthermore, as a consequence of our findings, particularly the incidence of malignancies and the high percentage of patients aged >18 years, we stress the importance of collaboration with adult clinicians to guarantee regular multi-specialist follow-up. In conclusion, this study highlights the importance of national registries to increase our understanding and improve management of this complex disease.     

Spontaneous regeneration of cochlear supporting cells after neonatal ablation ensures hearing in the adult mouse

Supporting cells in the cochlea play critical roles in the development, maintenance, and function of sensory hair cells and auditory neurons. Although the loss of hair cells or auditory neurons results in sensorineural hearing loss, the consequence of supporting cell loss on auditory function is largely unknown. In this study, we specifically ablated inner border cells (IBCs) and inner phalangeal cells (IPhCs), the two types of supporting cells surrounding inner hair cells (IHCs) in mice in vivo. We demonstrate that the organ of Corti has the intrinsic capacity to replenish IBCs/IPhCs effectively during early postnatal development. Repopulation depends on the presence of hair cells and cells within the greater epithelial ridge and is independent of cell proliferation. This plastic response in the neonatal cochlea preserves neuronal survival, afferent innervation, and hearing sensitivity in adult mice. In contrast, the capacity for IBC/IPhC regeneration is lost in the mature organ of Corti, and consequently IHC survival and hearing sensitivity are impaired significantly, demonstrating that there is a critical period for the regeneration of cochlear supporting cells. Our findings indicate that the quiescent neonatal organ of Corti can replenish specific supporting cells completely after loss in vivo to guarantee mature hearing function.Inner hair cells (IHCs), the sensory cells of the mammalian auditory sensory epithelium, are surrounded by specialized supporting cells (SCs) called “inner border cells” (IBCs) and “inner phalangeal cells” (IPhCs) (Fig. S1A). IBCs and IPhCs, together with other SCs, are known to play critical roles during the development and maturation of the organ of Corti, in processes such as patterning of the epithelium, synaptogenesis, and initiation of electrical activity in auditory nerves before the onset of hearing and formation of extracellular matrices (1–7). SCs also are essential for the function of the mature organ of Corti, where they contribute to the maintenance of the reticular lamina at the apical surface of the epithelium (8), control the extracellular concentration of ions (e.g., K⁺) (9, 10) and neurotransmitters (e.g., glutamate) (11), and support hair cell (HC) and auditory sensory neuron survival (5, 12–15). SCs also have been proposed to regulate the effects of insults on HCs by releasing molecules that either promote (e.g., ERK1 and 2) (16) or reduce (e.g., heat shock protein 70) (17) HC death. Additionally, SCs impact the extent of damage in the auditory epithelium through scar formation and clearance of HC debris (18). Furthermore, SCs are considered a potential source of cells for HC replacement in mammals, because SCs are a documented source of new HCs in cultured neonatal cochlea (19) and in adult utricles (20). Additionally, nonmammalian vertebrates regenerate HCs and SCs after damage and recover hearing, with the SCs being the source of the regenerative response (21–23). Indeed, if SCs are damaged by insults, the regenerative response is severely compromised (1, 24). Thus, it is assumed that the presence of these cells in the postnatal cochlea is essential for hearing, but specific roles of IBCs and IPhCs in HC maintenance and cochlear function have not been established.To determine the consequences of neonatal IBC and IPhC loss on the mature organ of Corti, we ablated these cells in vivo using an inducible diphtheria toxin fragment A (DTA) transgenic approach (25). Unexpectedly, we found that when these IHC supporting cells are eliminated immediately after birth, they are replaced efficiently within days. Moreover, this regeneration preserves the structure and function of the organ of Corti, so that mice with transient IBC/IPhC loss retain normal hearing as adults. In contrast, IBCs and IPhCs do not regenerate if ablation occurs after the onset of hearing, resulting in IHC loss and severe hearing impairment. Our studies also indicate that IBC and IPhC replacement in the neonatal cochlea results from transdifferentiation of less-specified SCs within the neighboring greater epithelial ridge (GER or Kölliker’s organ), which does not require cell proliferation. The unexpected regenerative capacity of SCs in the early postnatal organ of Corti in vivo may provide new strategies to regenerate its nonsensory and sensory cells after damage.     

Gastrointestinal bleeding as presentation of small bowel metastases of malignant melanoma: Is surgery a good choice?

INTRODUCTIONMelanoma shows a particular predilection in involving small intestine both in a single site and in multiple localization and acute or chronic gastrointestinal bleedings are often the first sign of tumour.PRESENTATION OF CASEWe report two cases of GI metastases of malignant melanoma, one presented with only a big mass that cause intestinal obstruction and the other with a tumour spread throughout the small intestine that produce enterorrhagia.DISCUSSIONDiagnosis and follow-up are very difficult: CT scan, PET-CT scan and capsule endoscopy should be complementary for the assessment of patients with GI symptoms and melanoma history.CONCLUSIONWhat is the role of surgery? Several studies suggest metastasectomy to achieve both R0 results and palliative resolutions of acute symptoms, such as obstruction, pain, and bleeding.     

Baseline glycated hemoglobin levels are associated with duodenal-jejunal bypass liner-induced weight loss in obese patients

Introduction

Endoscopic treatment with the duodenal-jejunal bypass liner (DJBL) leads to significant weight loss in obese patients. We sought to identify clinical factors associated with weight loss in obese patients treated with the DJBL for 1 year.

Methods

Subjects with morbid obesity were enrolled in a single-arm, open-label, prospective trial and implanted with the DJBL. Patient demographics along with baseline comorbidities, anthropometrics, and biochemical variables were selected for univariate and multivariate analysis.

Results

The DJBL was implanted in 79 subjects and 61 completed 12 months of follow-up. There were 18 early removals. Baseline mean age and body mass index (BMI) were 35.4 ± 9.7 years and 43 ± 5.6 kg/m², respectively. Forty-four (72 %) were women. This population included 22 subjects with type 2 diabetes (T2DM). Twelve months after treatment, patients had a mean excess body weight loss (%EBWL) of 46 ± 18 %. Univariate analysis identified that fasting glycemia (r ² = ?0.303, p < 0.013), insulin-resistance determined by HOMA-IR (r ² = ?0.457, p < 0.019), and glycated hemoglobin (HbA1c) (r ² = ?0.471, p < 0.013) were associated inversely with %EBWL at 1 year. In this cohort of patients, the multivariate analysis indicated that only baseline HbA1c levels were associated inversely with %EBWL after 1 year of treatment (β adjusted coefficient ?0.758, p < 0.016). Importantly, no differences at 1 year in %EBWL were observed between patients with or without T2DM (%EBWL T2D 46.7 ± 20 % vs. non-T2DM 46.8 ± 18.6 %, p = 0.988).

Conclusions

This analysis indicates that higher baseline HbA1c levels are associated independently with diminished body weight loss in obese patients treated with the DJBL independent of their diabetic status. These results show that DJBL induces clinically significant weight loss in both T2DM and non-T2DM patients.     

Psychosexual outcome after labiaplasty: a prospective case-comparison study

Introduction and hypothesis

Our goal was to determine psychosexual outcome after labiaplasty in the long-term with specific measures of genital body image and sexual dysfunction.

Method

We conducted a prospective study with a matched-comparison group of women not wanting labiaplasty. Forty-nine women were compared against a group of 39 women matched for age, sexual orientation, ethnicity, and marital status. The labiaplasty group was assessed before, 3 months after and between 11 and 42 months after surgery. The comparison group was assessed at two time points 3 months apart to control for the passage of time. The primary outcome measure was the Genital Appearance Satisfaction (GAS) scale.

Results

Of the 49 women receiving labiaplasty, 19 (38.8 %) were lost to follow-up but were reassessed clinically. Twenty-four of 25 (96 %) women in the labiaplasty group showed a reliable and clinically significant improvement on the GAS scale 3 months after the procedure; 21/23 (91.3 %) showed an improvement at the long-term follow-up. A large effect size was found for improvements on the GAS scale in the labiaplasty group. Small-effect sizes were found for improvements in sexual functioning. Nine women obtaining labiaplasty met diagnostic criteria for body dysmorphic disorder before the operation; eight lost that diagnosis at the 3-month follow-up; 26 % reported minor side effects.

Conclusions

Labiaplasty is effective in improving genital appearance and sexual satisfaction, but larger studies are required to determine the prevalence of potential side effects.     

Myxoid glioneuronal tumor,PDGFRA p.K385‐mutant: clinical,radiologic, and histopathologic features

“Myxoid glioneuronal tumor, PDGFRA p.K385‐mutant” is a recently described tumor entity of the central nervous system with a predilection for origin in the septum pellucidum and a defining dinucleotide mutation at codon 385 of the PDGFRA oncogene replacing lysine with either leucine or isoleucine (p.K385L/I). Clinical outcomes and optimal treatment for this new tumor entity have yet to be defined. Here, we report a comprehensive clinical, radiologic, and histopathologic assessment of eight cases. In addition to its stereotypic location in the septum pellucidum, we identify that this tumor can also occur in the corpus callosum and periventricular white matter of the lateral ventricle. Tumors centered in the septum pellucidum uniformly were associated with obstructive hydrocephalus, whereas tumors centered in the corpus callosum and periventricular white matter did not demonstrate hydrocephalus. While multiple patients were found to have ventricular dissemination or local recurrence/progression, all patients in this series remain alive at last clinical follow‐up despite only biopsy or subtotal resection without adjuvant therapy in most cases. Our study further supports “myxoid glioneuronal tumor, PDGFRA p.K385‐mutant” as a distinct CNS tumor entity and expands the spectrum of clinicopathologic and radiologic features of this neoplasm.     

Association of MASP2 polymorphisms and protein levels with rheumatic fever and rheumatic heart disease

MASP-2 is a key protein of the lectin pathway of complement system. Several MASP2 polymorphisms were associated with MASP-2 serum levels or functional activity. Here we investigated a possible association between MASP2 polymorphisms and MASP-2 serum levels with the susceptibility to rheumatic fever (RF) and rheumatic heart disease (RHD). We haplotyped 11 MASP2 polymorphisms with multiplex sequence-specific PCR in 145 patients with history of RF from south Brazil (103 with RHD and 42 without cardiac lesion [RFo]) and 342 healthy controls. MASP-2 levels were determined by ELISA. The low MASP-2 producing p.377A and p.439H variants were negatively associated with RF (P = 0.02, OR = 0.36) and RHD (P = 0.01, OR = 0.25). In contrast, haplotypes that share the intron 9 – exon 12 g.1961795C, p.371D, p.377V and p.439R polymorphisms increased the susceptibility to RHD (P = 0.02, OR = 4.9). MASP-2 levels were associated with MASP2 haplotypes and were lower in patients (P < 0.0001), which may reflect protein consumption due to complement activation. MASP2 gene polymorphisms and protein levels seem to play an important role in the development of RF and establishment of RHD.