Candidacy and long-term outcomes of subcutaneous implantable cardioverter-defibrillators in current practice in patients with hypertrophic cardiomyopathy.

BACKGROUND: In patients with Hypertrophic Cardiomyopathy (HCM) S-ICD is usually the preferred option as pacing is generally not indicated. However, limited data are available on its current practice adoption and long-term follow-up. METHODS: Consecutive HCM patients with S-ICD implanted between 2013 and 2021 in 3 international centers were enrolled in this observational study. Baseline, procedural and follow-up data were regularly collected. Efficacy and safety were compared with a cohort of HCM patients implanted with a tv-ICD. RESULTS: Seventy patients (64% males) were implanted with S-ICD at 41 ± 15 years, whereas 168 patients with tv-ICD at 49 ± 16 years. For S-ICD patients, mean ESC SCD risk score was 4,5 ± 1.9%: 25 (40%) at low-risk, 17 (27%) at intermediate and 20 (33%) at high-risk. Patients were followed-up for 5.1 ± 2.3 years. Two patients (0.6 per 100-person-years, vs 0.4 per 100 person-years with tv-ICD, p = 0.45) received an appropriate shock on VF, 17 (24%) were diagnosed with de-novo AF. Inappropriate shocks occurred in 4 patients (1.2 per 100-person-years, vs 0.9 per 100 person-years with tv-ICD, p = 0.74), all before Smart-Pass algorithm implementation. Four patients experienced device-related adverse events (1.2 per 100-person-years, vs 1 per 100 person-years with tv-ICD, p = 0.35%). CONCLUSIONS: S-ICDs were often implanted in patients with an overall low-intermediate ESC SCD risk, reflecting both the inclusion of additional risk markers and a lower decision threshold. S-ICDs in HCM patients followed for over 5 years showed to be effective in conversion of VF and safe. Greater scrutiny may be required to avoid overtreatment in patients with milder risk profiles.

Evolution and impact of a dedicated ultrasound clinic on clinical rheumatology practice at an academic medical center.

BACKGROUND: Rheumatologic ultrasonography (RhUS) has grown in scope and application over the past 20 years. While many studies have shown the benefits of RhUS, few have investigated the efficacy of a dedicated clinic. This study explores the impact of a dedicated ultrasound clinic on patients and rheumatologists at an academic medical center (AMC). METHODS: We analyzed claims data for patient visits, X-rays (XR), magnetic resonance imaging (MRI), and RhUS from an AMC with an established RhUS clinic, alongside two affiliated community medical practices (CMPs) without RhUS. We also analyzed RhUS clinic records on referral indication, procedures, results, and follow-up treatment changes. Pre- and post-RhUS visit patient surveys and referring physician (RP) surveys assessed experience and impact of the RhUS clinic. RESULTS: From 2018 to 2021, referrals to the RhUS clinic substantially increased. In parallel, XR and MRI orders changed by -76 % and -43 % respectively, compared with 163 % and -24 % at CMPs. Discordance between RP pre-RhUS assessments and RhUS results were common. Patient surveys showed RhUS led to increased disease understanding and impacted thoughts and decisions about their therapy. RPs found utility in RhUS across a range of indications and were confident with RhUS results. CONCLUSIONS: These findings suggest a dedicated RhUS clinic can be a valuable resource in clinical rheumatology practice. Implementation of a RhUS clinic at this AMC spurred rapid adoption of RhUS into clinical decision-making with notable benefits for patients and physicians alike. This may serve as a model for implementation of similar clinics at other institutions.

Biologics Initiation in Rheumatoid Arthritis by Race and Ethnicity: Results From a Randomized Survey Study.

OBJECTIVE: To investigate whether the race and ethnicity of a patient with rheumatoid arthritis (RA) influences rheumatologists' likelihood of choosing to initiate biologic disease-modifying antirheumatic drug (bDMARD) treatment. METHODS: We conducted a randomized survey experiment in which identical brief case vignettes of hypothetical patients with RA were sent to US rheumatologists (respondents). Three of the four cases included some level of treatment decision ambiguity whereas the fourth case strongly favored bDMARD initiation. Each respondent was shown the four case vignettes, with the race and ethnicity (Black, Hispanic, White) randomly assigned for each case. Each vignette offered multiple choices for next therapeutic step, which we summarized using frequencies and proportions by race and ethnicity version. RESULTS: Among 159 US rheumatologists, we found that for the three cases with some level of treatment decision ambiguity, there was little to no variability in the proportions of respondents who chose to start a biologic for the Black and Hispanic variants (cases 1, 2, and 3). For case 4, respondents generally agreed to start a biologic with some minimal variability across the variants (92.6% for the Black version, 98.1% for the Hispanic version, and 96.2% for the White version). CONCLUSION: There are conflicting data regarding bDMARD use and initiation in patients with RA based on the sex and race of the patient. This work adds to this conversation by examining how the next therapeutic step chosen by rheumatologists varied by the race and ethnicity of the hypothetical patient.

Lung Ultrasound in Children With Systemic Juvenile Idiopathic Arthritis-Associated Interstitial Lung Disease.

OBJECTIVE: Systemic juvenile idiopathic arthritis (JIA) associated with lung disease (JIA-LD) is a potentially life threating complication in children with systemic JIA. Although high-resolution computed tomography (HRCT) is considered the gold standard imaging modality for evaluating interstitial lung disease (ILD), lung ultrasound (US) has shown utility for ILD screening in adults with connective tissue diseases at lower cost and without using ionizing radiation. The goals of this pilot study were to describe lung US features in children with known systemic JIA-LD and to assess the feasibility of lung US in this population. METHODS: Children age <18 years with systemic JIA-LD and healthy controls were enrolled. Lung US acquisition was performed at 14 lung positions. Demographic, clinical, and HRCT data were collected and reviewed. Feasibility was assessed through patient surveys. Lung US findings were qualitatively and semiquantitatively assessed and compared to HRCT findings. RESULTS: Lung US was performed in 9 children with systemic JIA-LD and 6 healthy controls and took 12 minutes on average to perform. Lung US findings in systemic JIA-LD included focal to diffuse pleural irregularity, granularity, and thickening, with associated scattered or coalesced B-lines, and subpleural consolidations. Lung US findings appeared to correspond to HRCT findings. CONCLUSION: Lung US in systemic JIA-LD reveals highly conspicuous abnormalities in the pleura and subpleura that appear to correlate with peripheral lung findings on HRCT. Lung US is a feasible imaging tool in children even from an early age. This study suggests a potential role of lung US in systemic JIA-LD screening, diagnosis, and/or prognostication.

Antitumoral synergism between a copper(II) complex and cisplatin improves in vitro and in vivo anticancer activity against melanoma, lung and breast cancer cells.

BACKGROUND: Intrinsic resistance of cancer cells is a major concern for the success of chemotherapy, and this undesirable feature stimulates further research into the design of new compounds and/or alternative multiple drug chemotherapy protocols. METHODS: In this study, we investigated the antitumoral potential of the coordination compounds [Cu(HPClNOL)Cl]Cl (1), [Fe(HPClNOL)Cl2]NO3(2) and [Mn(HPClNOL)Cl2] (3). Using the human, MCF-7 and A549, and the murine melanoma, B16-F10, cell lines, we determined the cytotoxicity, DCFH oxidation, disruption of mitochondrial membrane potential (ΔΨm), Sub-G1 and TUNEL positive cells, and caspase 8 and 9 activities. Fractional inhibitory concentration (FIC) and xenograft models were also assessed to evaluate the efficacy of antitumoral potential. RESULTS: We observed that only complex 1 was cytotoxic. The treatment of cancer cells with complex 1 triggered ROS generation and promoted the disruption of ΔΨm. Complex 1 increased the number of Sub-G1 and TUNEL positive cells, and the measurement of caspase 8 and 9 activity confirmed that apoptosis was triggered by the intrinsic pathway. FIC demonstrated that the combination of complex 1 with cisplatin was additive for the A549 cells whilst it was synergic for MCF-7 and B16-F10. Treatment with complex 1, either alone or combined with cisplatin, reduced tumor growth on xenograft models. CONCLUSIONS: The present study brings new clues regarding the mechanism of action of [Cu(HPClNOL)Cl]Cl, either alone or in combination with cisplatin. GENERAL SIGNIFICANCE: These results indicate that complex 1, administered either singly or in combination with current drugs, has real potential for use in cancer therapy.

Tailored ultrasound learning for acute care surgeons: a review of the MUSEC (Modular UltraSound ESTES Course) project.

PURPOSE: The European Society for Trauma and Emergency Surgery (ESTES) identified the need for general and trauma surgeons involved in the management of critically ill surgical patients to embrace and learn both basic and advanced US skills. A steering group was created to address this deficit. METHODS: Modular UltraSound ESTES Course (MUSEC) is a modular blended-learning course. It incorporates pre-test/post-test examinations, pre-course online materials, didactic and interactive lectures, interactive case scenarios discussion with pathological US clips, hands-on practice on healthy volunteer models, and on original phantoms for simulating both pathological US findings and practicing US-guided interventional maneuvers. Four independent modules were provided. Surgical decision-making didactics were also included in the course curriculum. Learning gain (Δ of the rating of pre-test and post-test) was calculated for each module. An anonymous post-course satisfaction survey was also administered (16 questions with a Likert's 5-point scale of evaluation). RESULTS: Twenty-three MUSEC Courses were run in a 30 months period, training 416 doctors from 29 countries. A total of 52 modules were delivered. The mean pre-test and post-test grades were 8.3/12 and 10.7/12, respectively, yielding a significant mean learning gain of 28.9 % (p = 0.001). Post-course satisfaction survey got an overall ranking of 4.5/5. CONCLUSIONS: MUSEC is an effective and original educational format, enjoyed by candidates, that fills an educational gap for tailored US education as a procedural skill to acute care surgeons. Ongoing revisions should reduce the current limitations and increase the educational value, in terms of number of modules and post-course credentialing.

Whole-exome sequencing in obsessive-compulsive disorder identifies rare mutations in immunological and neurodevelopmental pathways.

Studies of rare genetic variation have identified molecular pathways conferring risk for developmental neuropsychiatric disorders. To date, no published whole-exome sequencing studies have been reported in obsessive-compulsive disorder (OCD). We sequenced all the genome coding regions in 20 sporadic OCD cases and their unaffected parents to identify rare de novo (DN) single-nucleotide variants (SNVs). The primary aim of this pilot study was to determine whether DN variation contributes to OCD risk. To this aim, we evaluated whether there is an elevated rate of DN mutations in OCD, which would justify this approach toward gene discovery in larger studies of the disorder. Furthermore, to explore functional molecular correlations among genes with nonsynonymous DN SNVs in OCD probands, a protein-protein interaction (PPI) network was generated based on databases of direct molecular interactions. We applied Degree-Aware Disease Gene Prioritization (DADA) to rank the PPI network genes based on their relatedness to a set of OCD candidate genes from two OCD genome-wide association studies (Stewart et al., 2013; Mattheisen et al., 2014). In addition, we performed a pathway analysis with genes from the PPI network. The rate of DN SNVs in OCD was 2.51 × 10(-8) per base per generation, significantly higher than a previous estimated rate in unaffected subjects using the same sequencing platform and analytic pipeline. Several genes harboring DN SNVs in OCD were highly interconnected in the PPI network and ranked high in the DADA analysis. Nearly all the DN SNVs in this study are in genes expressed in the human brain, and a pathway analysis revealed enrichment in immunological and central nervous system functioning and development. The results of this pilot study indicate that further investigation of DN variation in larger OCD cohorts is warranted to identify specific risk genes and to confirm our preliminary finding with regard to PPI network enrichment for particular biological pathways and functions.

ESTES guidelines: acute mesenteric ischaemia.

PURPOSE: Acute mesenteric ischaemia (AMI) accounts for about 1:1000 acute hospital admissions. Untreated, AMI will cause mesenteric infarction, intestinal necrosis, an overwhelming inflammatory response and death. Early intervention can halt and reverse this process leading to a full recovery, but the diagnosis of AMI is difficult and failure to recognize AMI before intestinal necrosis has developed is responsible for the high mortality of the disease. Early diagnosis and prompt treatment are the goals of modern therapy, but there are no randomized controlled trials to guide treatment and the published literature contains a high ratio of reviews to original data. Much of that data comes from case reports and often small, retrospective series with no clearly defined treatment criteria. METHODS: A study group of the European Society for Trauma and Emergency Surgery (ESTES) was formed in 2013 with the aim of developing guidelines for the management of AMI. A comprehensive literature search was performed using the Medical Subject Heading (MeSH) thesaurus keywords "mesenteric ischaemia", "bowel ischaemia" and "bowel infarction". The bibliographies of relevant articles were screened for additional publications. After an initial systematic review of the literature by the whole group, a steering group formulated questions using a modified Delphi process. The evidence was then reviewed to answer these questions, and recommendations formulated and agreed by the whole group. RESULTS: The resultant recommendations are presented in this paper. CONCLUSIONS: The aim of these guidelines is to provide recommendations for practice that will lead to improved outcomes for patients.

[Rennet production by Rhizomucor miehei NRRL 3169]. / Producción de renina por Rhizomucor miehei NRRL 3169.

The production of rennet was studied, using different strains of the fungus Rhizomucor miehei. The selection and preservation of strains, type of growth, media design and operation conditions were evaluated. The experiments were carried out in Erlenmeyer flasks in rotary shaker at 250 rpm and 2.5 eccentricity, and in mechanically stirred fermentors of the New Brunswick type, at 30 degrees C. In the studies concerning strain selection, the best strain was Rhizomucor miehei NRRL 3169. The major titles of enzyme were obtained in batch process at 168 h, with 884 SU/ml, whereas in mechanically stirred fermentors the best value was 1160 SU/ml. These values were far more superior to former ones published by various experts.

Producción de renina por Rhizomucor miehei NRRL 3169 / [Rennet production by Rhizomucor miehei NRRL 3169]

The production of rennet was studied, using different strains of the fungus Rhizomucor miehei. The selection and preservation of strains, type of growth, media design and operation conditions were evaluated. The experiments were carried out in Erlenmeyer flasks in rotary shaker at 250 rpm and 2.5 eccentricity, and in mechanically stirred fermentors of the New Brunswick type, at 30 degrees C. In the studies concerning strain selection, the best strain was Rhizomucor miehei NRRL 3169. The major titles of enzyme were obtained in batch process at 168 h, with 884 SU/ml, whereas in mechanically stirred fermentors the best value was 1160 SU/ml. These values were far more superior to former ones published by various experts.

Ultrasonographic contrast agent: evaluation of time-intensity curves in the characterisation of solitary thyroid nodules.

PURPOSE: To evaluate whether the time-intensity curve can improve characterisation of solitary thyroid nodules. MATERIAL AND METHODS: From June to December 2000 we studied 61 patients (16 men and 45 women, mean age 46 years) with solitary thyroid nodules that were not associated with any important hormonal alteration and that showed poor tracer uptake at scintigraphy. We evaluated the Power Doppler vascular pattern before and after a 60" intravenous injection of 2.5 g of Levovist (diluted in 7 ml). The study lasted 5 minutes from the beginning of the infusion. Finally, the time-intensity curves were processed. All the nodules underwent fine needle aspiration biopsy (FNAB) and excision biopsy. RESULTS: Histology revealed 43 benign lesions and 18 malignant lesions. At contrast-enhanced Power Doppler 83.4% (15/18) of the malignant nodules were found to be hypervascularized, while 16.6% (3/18) were hypovascularized. Of the benign lesions, 90.7% (39/43) were hypervascularized, 9.3% (4/43) were hypovascularized. All the nodules, both hyper- and hypovascularized, displayed rapid and intense wash-in curves. By contrast, the wash-out curves were regular and monophasic in 40/43 (93%) benign lesions (36 hypervascularized and 4 hypovascularized lesions) and irregular and polyphasic in 16/18 (89%) malignant lesions (13 hypervascularized and 3 hypovascularized lesions); 3/43 (7%) benign nodules showed polyphasic wash-out and 2/18 malignant lesions (11%) showed monophasic wash-out. DISCUSSION AND CONCLUSIONS: Time-intensity curves, and particularly wash-out curves, provide useful information for the characterisation of solitary thyroid nodules. 93% of benign nodules (with regular vascularization) showed a monophasic pattern of the wash-out curve, while 89% of malignant nodules ("anarchical" vascularization) had polyphasic wash-out curves. This behaviour was observed in both hypervascularized and hypovascularized lesions. Our method proved to have a sensitivity of 88% and a specificity of 93%. The study of time-intensity curves could therefore enable us to differentiate between benign and malignant lesions and characterise hypovascularized malignant nodules which would not be observed without contrast agent.

The hand in recessive dystrophic epidermolysis bullosa.

Recessive dystrophic epidermolysis bullosa is still a difficult challenge for surgeons and doctors. Hand retractions are different from burns. The medical team must have a good knowledge of the disease. Surgery must be performed with the collaboration of every member of the team, as well as the family. In young children, complete correction of the retractions is possible. On the other hand, when retractions are present for a long time in children and adolescents, surgery is purely functional. Static and dynamic splints delay recurrences, but their prolonged use presents psychological obstacles in adolescents and adults.

Influencia del amaranto en la producción de alpha-amilasa empleando Aspergillus niger NRRL 3112 / Influence of amaranth on the production of alpha-amylase using Aspergillus niger NRRL 3112

In this paper the influence of the amaranth seed meal and the aeration conditions on the alpha-amylase production by Aspergillus niger NRRL 3112 were studied. The assays of selection of culture medium were carried out in a rotary shaker at 250 rpm and 2.5 cm stroke. The aeration conditions were studied in a mechanically stirred fermentor New Brunswick type. A concentration of alpha-amylase of 2750 U.Dun/ml was achieved at 120 h with a dry weight of 8.0 g/l, using a base medium with 5.0 g/l Amaranthus cruentus seed meal. In the experiment performed in a New Brunswick fermentor, the highest value was 2806 U.Dun/ml. This result was obtained after 120 h, operating at 300 rpm and an airflow of 1 l/l. min. in a limited dissolved oxygen concentration. It was determined that the increase in the agitation rate was not favorable to the enzyme production, despite that an increase was verified in the dissolved oxygen. The morphology of the microorganism, in long and ramified hyphae, was the critical factor to obtain higher levels of alpha-amylase.

[Influence of amaranth on the production of alpha-amylase using Aspergillus niger NRRL 3112]. / Influencia del amaranto en la producción de alpha-amilasa empleando Aspergillus niger NRRL 3112.

In this paper the influence of the amaranth seed meal and the aeration conditions on the alpha-amylase production by Aspergillus niger NRRL 3112 were studied. The assays of selection of culture medium were carried out in a rotary shaker at 250 rpm and 2.5 cm stroke. The aeration conditions were studied in a mechanically stirred fermentor New Brunswick type. A concentration of alpha-amylase of 2750 U.Dun/ml was achieved at 120 h with a dry weight of 8.0 g/l, using a base medium with 5.0 g/l Amaranthus cruentus seed meal. In the experiment performed in a New Brunswick fermentor, the highest value was 2806 U.Dun/ml. This result was obtained after 120 h, operating at 300 rpm and an airflow of 1 l/l. min. in a limited dissolved oxygen concentration. It was determined that the increase in the agitation rate was not favorable to the enzyme production, despite that an increase was verified in the dissolved oxygen. The morphology of the microorganism, in long and ramified hyphae, was the critical factor to obtain higher levels of alpha-amylase.

Development of dopaminergic neurons in the human mesencephalon and in vitro effects of basic fibroblast growth factor treatment.

The origin and development of the mesencephalic dopaminergic (mesDA) neurons within the substantia nigra were characterized in human embryos from Postconception (PC) Week 5.0 to 12.0. Tyrosine hydroxylase (TH) immunoreactive cells were first demonstrated in the ventral mesencephalon at PC Week 5.5 next to the ventricular zone. Cell migration and neurite outgrowth of TH-positive neurons were timed. Early expression of ganglioside GM1 was demonstrated in developing neurons. Glial fibrillary acidic protein (GFAP) was first observed at PC Week 10.0 instead, after the dopaminergic neurotransmitter phenotype expression. In vitro complementary information was obtained: TH-positive cells represented about 3% of the total cell population after a week in culture, based upon accurate anatomical dissection. They tended to form microaggregates and to grow in close contact with glial cells. MesDA neuronal expression of TH activity was measured by a biochemical microassay. TH-positive cells responded to basic fibroblast growth factor (bFGF) both with increased TH activity and neuronal survival. bFGF effects were mediated by the proliferative action on glial cells. Astroglial GFAP-positive cells express nerve growth factor-low-affinity receptor in culture. Information on in vitro and in vivo sequences of mesDA neuronal development and their response to identified neurotrophic molecules may be invaluable for selection of the most appropriate tissue donor age for brain grafting and development of alternative treatment strategies for Parkinson's disease.

Maintained cellular function of adrenal medullary cells in parkinsonian dysautonomia.

Adrenal gland involvement in Parkinson's disease was reported by different authors. Further studies became relevant after adrenal was proposed as dopaminergic donor for neurotransplantation. Chromaffin cells were grown in culture and the effects of nerve growth factor (NGF) tested: no differences were observed between parkinsonian and control cells. The expression of the beta-NGF mRNA in the parkinsonian adrenal was analyzed: a specific cDNA was synthesized and a 168 bp portion amplified using PCR. The products were identified and the identity of the fragment was confirmed by sequencing. Quantitative PCR demonstrated a beta-NGF mRNA concentration exceeding 5 fg/micrograms of total adrenal RNA. These findings demonstrate the retained functional capacity of the parkinsonian adrenal to respond to NGF and express the beta-NGF mRNA.

[The role of episacroiliac lipomas as a cause of pseudolumbago-sciatica syndromes]. / Il ruolo dei lipomi episacroiliaci come causa di sindromi pseudolombosciatalgiche.

With their research, the authors intend to recall the existence of episacroiliac lipomas. These growths are important in as much as they cause low lumbar pain where the objective and instrumental signs typical of radicular lumbar syndromes are not present. Amongst other routine instrumental tests the echo scan is suggested for a more precise record. A simple operation relieves pain once and for all.

Human neuronal cells in culture: from concepts to basic methodology.

The paper reviews some conceptual and methodological aspects of the tissue culture models which, during the past three decades, demonstrated a remarkable mimicry of many important structures and functions of the mammalian Central Nervous System (CNS) and related peripheral sensory and motor elements. Emphasis is placed on an original human neuronal tissue culture model obtained from selective CNS areas. The different cell types were identified and the neurotrophic interactions preliminary characterized. Neuropathological findings suggest hypothesis that can be fully tested using in vitro human models of affected cerebral specific areas.

[Preliminary data on the endocrinologic evaluation of thalassemic adolescents]. / Dati preliminari sulla valutazione endocrinologica di adolescenti talassemici.

Endocrine disfunction are well known in young patients with thalassaemia major and are mainly due to iron overload. Gonadotrophin releasing hormone (GnRH) was administered to 13 boys aging more than 14 years and to 13 girls aging more than 13 years to assess pituitary function. Human Chorionic gonadotrophin (HCG) was also administered to 13 boys to evaluate their gonadal function. Most of the patients had evidence of pituitary hypofunction and in 4 boys there was evidence of gonadic failure. This study is mandatory for a correct therapeutic approach.