Implantation of cardioverter-defibrillator: Effects on shoulder function

Background

Subcutaneous almost substituted subpectoral approach of implantable cardioverter-defibrillator (ICD) implantation as a less invasive surgical technique. However, the impact of this change in placement site on procedure-related shoulder impairment is poorly understood.

Methods

Candidates for ICD implantation were prospectively evaluated at baseline, 2-weeks and 3-months after the procedure. Assessment of shoulder function included: Constant Score, Numeric Rating Scale (NRS) for pain and the Disability of the Arm, Shoulder and Hand (DASH) scoring method. The Short Form-36 (SF-36) questionnaire was adopted for quality of life.

Results

Fifty consecutive patients were enrolled (21 single-chamber, 5 dual-chamber and 24 biventricular ICD). Significant changes in the short term were observed: physical component summary (regarding SF-36) decreased from 44.5 ± 9.1 to 41.8 ± 11.4 (p = 0.016), patients with NRS > 1 increased from 14% to 44% (p < 0.001), DASH score increased from 1.29 [interquartile range 0.00–10.34] to 30.60 [interquartile range 12.93–46.34] (p < 0.001). Notably, only the shoulder ipsilateral to implantation site presented a decrease in Constant Score (76.00 [interquartile range 61.37–86.87] vs. 95.75 [interquartile range 91.37–98.00]; p < 0.001). After three months most of the parameters seemed to have recovered, except for range of motion. Procedure-related increase in pain (i.e. NRS increase ≥ 1 point) was the most important independent predictor of shoulder impairment, in terms of Constant Score modification (r = 0.570; p < 0.001).

Conclusions

ICD implantation is frequently associated with ipsilateral shoulder impairment which tends to recover within 3-months. These data positively compare with the subpectoral approach and should be considered for future research regarding impact of ICD implant on physical well-being and quality of life.     

Persistent activation of DNA damage signaling in response to complex mixtures of PAHs in air particulate matter

Complex mixtures of polycyclic aromatic hydrocarbons (PAHs) are present in air particulate matter (PM) and have been associated with many adverse human health effects including cancer and respiratory disease. However, due to their complexity, the risk of exposure to mixtures is difficult to estimate. In the present study the effects of binary mixtures of benzo[a]pyrene (BP) and dibenzo[a,l]pyrene (DBP) and complex mixtures of PAHs in urban air PM extracts on DNA damage signaling was investigated. Applying a statistical model to the data we observed a more than additive response for binary mixtures of BP and DBP on activation of DNA damage signaling. Persistent activation of checkpoint kinase 1 (Chk1) was observed at significantly lower BP equivalent concentrations in air PM extracts than BP alone. Activation of DNA damage signaling was also more persistent in air PM fractions containing PAHs with more than four aromatic rings suggesting larger PAHs contribute a greater risk to human health. Altogether our data suggests that human health risk assessment based on additivity such as toxicity equivalency factor scales may significantly underestimate the risk of exposure to complex mixtures of PAHs. The data confirms our previous findings with PAH-contaminated soil (Niziolek-Kierecka et al., 2012) and suggests a possible role for Chk1 Ser317 phosphorylation as a biological marker for future analyses of complex mixtures of PAHs.     

Vitreous incarceration in sutured vs non-sutured sclerotomies after 25-gauge macular surgery

ObjectivesTo study the patterns of vitreous incarceration in sutured vs non-sutured sclerotomies in patients subjected to 25-gauge macular surgery.MethodsA prospective study of 135 eyes affected by epiretinal membrane or macular hole. Vitreal disposition was evaluated via ultrasound biomicroscopy (UBM) at the sclerotomy sites between 30 and 40 days after surgery, once the tamponade had completely disappeared.ResultsIn total, 349 sclerotomies (86.2%) of 99 patients were non-sutured while 56 sclerotomies (13.8%) of 36 patients were sutured at the end of the surgical procedure. Among the 36 patients with sutured sclerotomies, 15 out of 36 (41.6%) had at least two sclerotomies sutured. All the sclerotomy sites were evaluated (405 sclerotomies). Sclerotomy suture was significantly associated with a less aggressive pattern of vitreal incarceration (OR: 0.16, 95% CI: 0.07–0.35, p < 0.001). Compared to preoperative values, day 1 post operative IOP was not significantly different in patients with sutured sclerotomies, while patients with non-sutured sclerotomies had a significantly lower day 1 post operative IOP.ConclusionsIn 25-gauge macular surgery, UBM evaluation documented a higher rate of postoperative vitreous incarceration in the non-sutured sclerotomies, confirming the previously postulated role of the residual vitreous, left at the end of the surgery, in closing the sclerotomy site.Subject terms: Surgery, Retinal diseases     

Ten-year experience with penile prosthetic surgery for the treatment of erectile dysfunction:outcomes of a tertiary referral center and predictors of early prosthetic infection

We aimed to evaluate ten-year outcomes of penile prosthesis(PP)implantation for the treatment of erectile dysfunction and to assess predictors of early prosthet...     

Modulation of vascular tone control under isometric muscular stress: Role of estrogen receptors

AimsThe aim of this study was to evaluate isometric muscle contraction (handgrip) changes on key elements of cardiac afterload, before and after raloxifene administration in postmenopausal women.Methods/results12 postmenopausal and 12 fertile women were studied. Postmenopausal women underwent raloxifene administration (60 mg/day for 30 days). We evaluated vascular reactivity in superficial palmar arterial arch during handgrip in postmenopausal women before and after (M + R) drug administration, and in controls. Blood flow was higher after raloxifene administration (p < 0.05). Mean arterial pressure (MAP)/mean arterial flow (Fmed) and arterial pulse pressure (APP)/systolic maximum arterial flow (Fmax syst) were lower after raloxifene administration (p < 0.001). Systolic blood pressure (SBP)/R-R ratio was higher in postmenopausal women than in the controls and M + R (p < 0.01). End-handgrip systolic and diastolic blood pressure were higher in patients before raloxifene administration than in controls (p < 0.001); diastolic and mean arterial pressure reduced after raloxifene administration (p < 0.001). End-effort APP/Fmax syst-ratio before treatment was higher than baseline (p < 0.05). Controls and no-treated patients showed a MAP/Fmed ratio at end-handgrip higher than M + R group and rest (p < 0.05). Handgrip reduced R-R interval and increased SBP/R-R ratio were shown in all groups (p < 0.05).ConclusionsRaloxifene reduced the vascular effects of isometric muscle contraction by modulating the vasomotor tone of peripheral vessels in relation to exercise.     

Dual Diagnosis and Chronology of Illness in Treatment-Seeking Italian Patients Dependent on Heroin

ABSTRACT

Although there are studies describing the prevalence of patients with drug addiction and dual diagnosis, there is a paucity of data regarding the progression from psychiatric disorders to drug addiction or vice versa. A total of 1,090 patients dependent on heroin were interviewed to examine the presence of dual diagnosis and the progression from psychiatric disorders to drug dependence or vice versa. A total of 574 patients met the criteria for a dual diagnosis. A total of 362 patients progressed from substance abuse disorders to psychiatric disorders (SUD-PR) and 144 patients progressed from psychiatric disorders to drug addiction (PSY-PR). SUD-PR patients are more frequently affected by mood disorders. PSY-PR patients were more frequently diagnosed as psychotic or affected by anxiety disorders. The authors’ findings suggest that the self-medication theory of dual diagnosis was relevant only for those with existing diagnoses of schizophrenia or anxiety disorders. When treating patients with a dual diagnosis, clinicians should ensure that the same attention is given to the treatment of drug dependence as it is to the treatment of comorbid psychiatric conditions.     

Mineralization of 3D Osteogenic Model Based on Gelatin-Dextran Hybrid Hydrogel Scaffold Bioengineered with Mesenchymal Stromal Cells: A Multiparametric Evaluation

Gelatin–dextran hydrogel scaffolds (G-PEG-Dx) were evaluated for their ability to activate the bone marrow human mesenchymal stromal cells (BM-hMSCs) towards mineralization. G-PEG-Dx1 and G-PEG-Dx2, with identical composition but different architecture, were seeded with BM-hMSCs in presence of fetal bovine serum or human platelet lysate (hPL) with or without osteogenic medium. G-PEG-Dx1, characterized by a lower degree of crosslinking and larger pores, was able to induce a better cell colonization than G-PEG-Dx2. At day 28, G-PEG-Dx2, with hPL and osteogenic factors, was more efficient than G-PEG-Dx1 in inducing mineralization. Scanning electron microscopy (SEM) and Raman spectroscopy showed that extracellular matrix produced by BM-hMSCs and calcium-positive mineralization were present along the backbone of the G-PEG-Dx2, even though it was colonized to a lesser degree by hMSCs than G-PEG-Dx1. These findings were confirmed by matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI), detecting distinct lipidomic signatures that were associated with the different degree of scaffold mineralization. Our data show that the architecture and morphology of G-PEG-Dx2 is determinant and better than that of G-PEG-Dx1 in promoting a faster mineralization, suggesting a more favorable and active role for improving bone repair.     

Prognostic value of 18F-DOPA PET/CT at the time of recurrence in patients affected by neuroblastoma

Purpose

The aim of this study was to investigate the relationship between ¹²³I-metaiodobenzylguanidine (MIBG) scan semi-quantification and a new ¹⁸F-DOPA positron emission tomography (PET)/CT score in patients with suspected or documented neuroblastoma (NB) relapse and to assess the association between these two parameters and progression-free survival (PFS)/overall survival (OS).

Methods

We analysed 24 NB patients who had undergone ¹²³I-MIBG and ¹⁸F-DOPA PET/CT scans at the time of suspected relapse, after applying a proper scoring system for each scan. In time-to-event analyses, the score distributions were regarded as continuous and were categorized in tertiles and medians. We used Kaplan-Meier curves and Cox proportional hazard models for PFS and OS in order to estimate the independent prognostic impact of ¹²³I-MIBG and ¹⁸F-DOPA PET/CT scans.

Results

The ¹²³I-MIBG and ¹⁸F-DOPA scores were highly and positively correlated (Spearman’s rho?=?0.8, p?<?0.001). Over a median follow-up of 14 months (range 6–82), 12 cases of disease progression and 6 deaths occurred. Multivariate Cox models showed a higher risk of disease progression [hazard ratio (HR) 17.0, 95 % confidence interval (CI) 2.7–109] in NB patients with ¹²³I-MIBG score?>?3 (3rd tertile) and an even higher risk (HR:37.2, 95 % CI 2.4–574) in those with ¹⁸F-DOPA whole-body metabolic burden (WBMB) >7.5 (median), after adjustment for all main clinical/pathological factors considered. Kaplan-Meier analyses showed a significant association with OS (log-rank p?=?0.01 and p?=?0.03 for ¹²³I-MIBG and ¹⁸F-DOPA WBMB, respectively).

Conclusion

Our results confirm the good agreement between ¹⁸F-DOPA PET/CT and ¹²³I-MIBG scan in patients affected by NB relapse. In time-to-event analyses, ¹²³I-MIBG scan and ¹⁸F-DOPA PET/CT scores were independently and significantly associated with disease progression.     

Vemurafenib and panitumumab combination tailored therapy in BRAF-mutated metastatic colorectal cancer: A case report

As the knowledge on cancer genetic alterations progresses, it fosters the need for more personalized therapeutic intervention in modern cancer management. Recently, mutations in KRAS, BRAF, and PIK3CA genes have emerged as important mechanisms of resistance to EGFR-targeted therapy in metastatic colorectal cancer (mCRC). Here we report the first case of a mCRC patient whose disease had progressed on standard lines of treatment and for which we devised a personalized therapeutic approach consisting of vemurafenib (Zelboraf^TM) and panitumumab (Vectibix^TM), based on the following molecular profile: BRAF^V600E-mutant, amplified EGFR (double positive) and WT KRAS, WT PIK3CA, not-amplified HER2 (triple negative). This new combination therapy was well tolerated and resulted in a strong control of the disease. In particular, the vemurafenib-panitumumab combination appears to limit the typical toxicity of single agents, since no cutaneous toxic effects typically associated with vemurafenib were observed. Here we report the first clinical evidence that the combination of an anti-EGFR (panitumumab) and an inhibitor of BRAF^V600E (vemurafenib) is well tolerated and results in a strong disease control in an extensively pretreated mCRC patient.