Blood glucose control and metabolic dysfunction-associated steatotic liver disease in people with type 1 diabetes.

PURPOSE: Metabolic dysfunction-associated steatotic liver disease (MASLD) may have distinctive pathophysiological features in type 1 diabetes (T1D). We evaluated the independent role of blood glucose control on MASLD in T1D. METHODS: In a cross-sectional study on 659 T1D adult patients, MASLD was assessed by the Fatty Liver Index (FLI) and the Hepatic Steatosis Index (HSI). Anthropometric, biochemical, and clinical parameters were retrieved from electronic records. Blood glucose control status was evaluated by dividing participants into subgroups according to the median value of HbA1c [7.6% (60 mmol/mol)], and this analysis was repeated excluding overweight/obese patients. RESULTS: Patients with HbA1c above 7.6% (60 mmol/mol) showed significantly higher MASLD indices (HSI 38 ± 6 vs. 36 ± 5, p < 0.001; FLI 26 ± 26 vs.19 ± 19, p < 0.001), and higher proportions of MASLD identified by HSI (57 vs. 44%, p < 0.001) and FLI (14 vs. 7%, p < 0.001) than patients with HbA1c below 7.6% (60 mmol/mol). Similar results were obtained for HSI after the exclusion of overweight/obese patients. Stepwise linear regression analysis confirmed that HbA1c was independently associated with HSI (r = 0.496, p = 0.009) and FLI (r = 0.722, p = 0.007); waist circumference with HSI (r = 0.492, p < 0.001); and waist circumference (r = 0.700, p < 0.001), HDL cholesterol (r = 0.719, p < 0.001), and LDL cholesterol (r = 0.712, p < 0.001) with FLI. CONCLUSIONS: Blood glucose control is a main factor associated with MASLD in adults with T1D, also independently of overweight and obesity. Appropriate therapeutic strategies focused on tight blood glucose control may also be needed for the prevention and treatment of MASLD in T1D.

New perspectives for transcatheter aortic valve implantation: more than a "simple" alternative to surgery.

To date, the gold standard of aortic stenosis treatment is surgical valve replacement. However, in inoperable or high risk patients a valid alternative is transcatheter aortic valve implantation (TAVI). Several trials showed feasibility, efficacy and safety of TAVI, with a tailored strategy for these patients on the basis of their clinical and anatomical conditions. The selection of valve type (CoreValve® or Edwards Sapien®) and transcatheter approach (transfemoral, transapical, subclavian or direct aortic approach) is an important step in the management of aortic stenosis. However, mortality is high and it is mainly related to non-cardiac reasons, given the high clinical risk profile of these patients. Moreover, the less invasive approach, the faster recovery, the reduced morbidity and the improved psychological tolerance, typical of TAVI, suggest that this technique could be used in a broader spectrum of cases, becoming a valid therapeutic alternative even in patients with severe aortic stenosis with a low surgical risk or asymptomatics. The identification of aortic stenosis patients by the medical community and their assessment over time, before they become candidates only for "extreme" strategies, remains the main challenge.

Effects of the Nuss procedure on chest wall kinematics in adolescents with pectus excavatum.

No data are available on the effects of the Nuss procedure on volumes of chest wall compartments (the upper rib cage, lower rib cage and abdomen) in adolescents with pectus excavatum. We used optoelectronic plethysmography to provide a quantitative description of chest wall kinematics before and 6 months after the Nuss procedure at rest and during maximal voluntary ventilation in 13 subjects with pectus excavatum. An average 11% increase in chest wall volume was accommodated within the upper rib cage (p=0.0001) and to a lesser extent within the abdomen and lower rib cage. Tidal volumes did not significantly change during the study. The repair effect on chest wall kinematics did not correlate with the Haller index of deformity at baseline. Six months of the Nuss procedure do increase chest wall volume without affecting chest wall displacement and rib cage configuration.

Chest wall kinematics in young subjects with Pectus excavatum.

Quantifying chest wall kinematics and rib cage distortion during ventilatory effort in subjects with Pectus excavatum (PE) has yet to be defined. We studied 24 patients: 19 during maximal voluntary ventilation (MVV) and 5 during MVV and cycling exercise (CE). By optoelectronic plethysmography (OEP) we assessed operational volumes in upper rib cage, lower rib cage and abdomen. Ten age-matched healthy subjects served as controls. Patients exhibited mild restrictive lung defect. During MVV end-inspiratory and end-expiratory volumes of chest wall compartments increased progressively in controls, whereas most patients avoided dynamic hyperinflation by setting operational volumes at values lower than controls. Mild rib cage distortion was found in three patients at rest, but neither in patients nor in controls did MVV or CE consistently affect coordinated motion of the rib cage. Rib cage displacement was not correlated with a CT-scan severity index. Conclusions, mild rib cage distortion rarely occurs in PE patients with mild restrictive defect. OEP contributes to clinical evaluation of PE patients.

Coronary flow reserve evaluation: basics, techniques and clinical applications.

Coronary flow reserve is a useful physiologic parameter providing information on coronary stenoses severity. To date, the gold standard to evaluate coronary flow reserve consists of fractional flow reserve (FFR) measurement, assessed with a pressure-wire. The FFR has a high lesion specificity, due to insensitivity to patient hemodynamic status and to coronary microvascular resistance; it shows low inter- and intraindividual variability and a well-defined, bound cut-off range values (0.75-0.80). Several reports confirmed that FFR has high reproducibility and feasibility in patients with either single- or multi-vessel coronary artery disease, or with both stable and instable coronary artery disease and that is significantly associated with patient outcome. More recently, the FFR has been used as a sensitive marker of successful percutaneous coronary intervention, since postprocedural FFR value strongly predicts patients event-free survival rate after angioplasty. Moreover, it has been demonstrated that abnormal FFR ratios can be also associated with diffused atherosclerotic coronary artery disease in the absence of unique angiographically detectable stenoses requiring revascularization. There are strong evidences supporting that the FFR provides crucial functional information that could be related with morphological endovascular ultrasound findings, with the possibility to achieve same information in a cheaper, easier and more available manner. This review will focus on the current available literature regarding coronary flow reserve quantification and its clinical validation, suggesting and highlighting its current and future clinical applications.

Coronary stenting early before non-cardiac surgery: is the endothelial progenitor cell capturing coronary stent a solution?

The authors report, for the first time, immediate and mid-term outcome of early antiplatelet therapy discontinuation followed by uneventful non-cardiac surgery and endovascular aortic repair, few days after successful deployment of an endothelial progenitor cell capturing coronary stent, in three consecutive patients.

Case for diagnosis: 4-month-old infant with increasing cough, hemoptysis, and anemia.

A 4-month-old caucasian infant presented non-productive cough, fever associated with hemoptysis, and increasing anemia. He had mild tachypnoea; routine lab tests were normal. The thoracic HRCT scan showed a very large mass in the right lung adherent to the thorax wall, well defined and limiting the medium and upper lobe; the mass was well vascularized, and with central hypodensic areas. Fiberoptic bronchoscopy and bronchoalveolar lavage (BAL) cytology were normal. The definitive histology of the mass showed the presence of inflammatory cells admixed with fibroblasts and rare Touton giant cells in the lesion suggestive of a juvenile xanthogranuloma (JXG) of the lung.

Total esophagogastric dissociation: 10 years' review.

PURPOSE: Neurologically impaired children run a 12% to 45% risk of recurrent gastroesophageal reflux (GER) after fundoplication. Elimination of the reflux by "rescue" total esophagogastric dissociation (TEGD) encouraged us to use it also as a "primary" form of antireflux surgery in this group of patients. METHODS: Twenty-six (14 male, 12 female) patients underwent TEGD between 1994 and 2004, of which 16 were primary and 10 were rescue procedures for failed fundoplication. RESULTS: There was no operative mortality and postoperative complications were limited to one subphrenic collection, one esophagojejunal dehiscence, and one small bowel hernia beneath the jejunal Roux loop. Gastrostomy feeding was usually established by 3 to 5 days and the mean hospital stay was 10.2 days (range, 6-18 days). At follow-up of 7 months to 11 years, there was no recurrence of GER. Four late deaths were unrelated to the surgery. The children's nutritional status improved with the mean weight standard deviation score showing a statistically significant increase from -2.63 preoperatively to -0.96 postoperatively (Wilcoxon's signed rank P value < or =.005). CONCLUSIONS: Total esophagogastric dissociation is a safe definitive solution for GER because it eliminates all risk of recurrent reflux. We therefore feel that TEGD can be used as a primary treatment of choice for severely neurologically impaired patients who are experiencing GER and are completely dependant on tube feeds.

Further experience with OK-432 for lymphangiomas.

This study includes all the children treated with OK-432 for lymphangioma at our institute. Twenty-nine children treated between 1999 and 2003 are reported for the first time: twelve cases regressed completely, eight cases regressed more than 50% and seven remained unchanged; two cases were lost at follow-up. The outcome was related to the size of the cysts, the larger ones having a better prognosis. The adverse reactions are discussed and the methods of treatment are described in detail. Fifteen children, treated before 1999 and already reported, are reviewed after a long-term follow-up. Four had a recurrence: one regressed spontaneously and three needed further treatment. The other 11 had no complaints. Even considering the risk of recurrence, OK-432 therapy remains our first line therapy for lymphangiomas, avoiding surgery in most cases.

[Role of mutilating surgery in the treatment of non-chemosensitive pediatric soft tissue sarcomas. Experience of the Italian Cooperative Group Studies RMS-79 and RMS-88]. / Ruolo della chirurgia mutilante nel trattamento dei sarcomi delle parti molli non chemiosensibili in età pediatrica. Esperienza degli studi Cooperativi Italiani RMS-79 ed RMS-88.

UNLABELLED: Aim of the study was to evaluate the role of mutilating surgery in the patients with non chemosensitive soft tissue sarcomas (STS) registered in the Italian Studies. Between 1979 and 1995, 114 patients (pts) with "non chemosensitive" localized STS were enrolled in the cooperative studies RMS-79 (33) and RMS-88 (81). Median age: 89 months (range 1-194). HISTOLOGY: fibrosarcoma 29, Malignant Perpheral Nerve Sheath Tumors (MPNST) 40, malignant fibrous histiocytoma 5, hemangiopericytoma 6, leiomyosarcoma 4, others 20, STS nos 10. The cases were classified according to the IRS staging system as Gr. I 46, Gr. II 24, Gr. III 44. Twelve out of 114 pts (7%), 5/33 (14%) in the first study and 7/81 (8%) in the second, underwent mutilating surgery: 8 pts (of whom 3 were < 2 y of age) had a fibrosarcoma and 4 a MPNST. The mutilating procedure was carried out at diagnosis in 6 cases (4 in RMS-79 and 2 in RMS-and 88) and achieved radicality in 5/6 cases. It was performed after ineffective chemotherapy (CT) in 5 pts (1 in RMS-79 and 4 in RMS-88). One pt (RMS-88) underwent mutilation after multiple local recurrences treated with CT, radiotherapy and conservative excisions (RMS-88) and died. The procedures consisted of 5 amputations, 4 demolitive excisions of extremities with functional impairment, 1 nephrectomy, 1 excision of deferents with spermatic vesicae and 1 mastectomy. OUTCOME: At present 6/12 pts, 5 with fibrosarcoma and 1 with MPNST, are alive with no evidence of disease (NED), 4 of the first and 2 of the second study. Of the 5 Gr. I patients, 4 are alive (NED) and 1 died of 2nd tumor; 1 Gr. II pt is alive NED; of the 5 Gr. III pts 1 is alive NED and 4 died (3 of metastatic spread and 1 of 2nd tumor); the pt amputated after repeated local relapses (Gr. II) is dead of pulmonary metastases. CONCLUSIONS: In the RMS-79 study the mutilations were frequent and were performed at diagnosis in several cases; this trend decreased in the 2nd study in which chemotherapy was attempted in most of the patients. Probably the timing of mutilating procedures was not always adequate (too early or too late). The outcome of pts undergone mutilations is similar to that of the whole group of 114 pts, whose overall survival at 10 years is 64% (C.I. 60-77). Only fibrosarcomas and MPNST probably requires a more aggressive surgical behaviour. At present we avoid initial demolitive surgery; it should be planned without delay after the first local relapse or after initial ineffective CT and RT.

Hepatic abscess and umbilical venous catheter: one cannot be cavalier about proper position.

PURPOSE The umbilical venous catheter (UVC) is routinely used in neonatal intensive care. Incorrect placement may expose the patient to some dangerous complications (i.e. thrombosis, abscesses, etc). We report a case of an hepatic abscess due to incorrect positioning of this device. We describe how the abscess was treated and we emphasize that one cannot be cavalier about proper positioning of the UVC.

Experimental abdominal wall defect repaired with acellular matrix.

In the surgical repair of congenital abdominal-wall defects (AWD), the ready availability of a non-immunogenic and non-prosthetic biomaterial that could guide the regeneration of normal tissue is a fascinating possibility. Biomaterials are already in use, but in our experience, an acellular matrix (ACM) can stimulate exact regeneration of the absent tissue. We explored the possibility of using an ACM to repair a muscular AWD in an animal model. Male New Zealand white rabbits (3-4 kg, n = 18) were anesthetized and the abdominal wall was shaved and scrubbed; a vertical incision was made in the left lower quadrant and a large patch of external-oblique muscle was resected (3 x 3 cm). The animals underwent reconstruction with homologous diaphragm acellular matrix (HDAM) grafts that were previously prepared using a detergent enzymatic method. The patches were evaluated histologically at 9 (n = 6), 40 (n = 6), and 90 (n = 6) days post-surgery in each group; moreover, 90 days post-surgery an electromyogram (EMG) (n = 6) of the implanted matrix was recorded. Histologic analysis demonstrated that the HDAM supported fibroblast migration, deposition of newly-formed collagen, and neovascularization. No signs of necrosis, or evidence of skeletal-muscle-cell ingrowth were detected. The EMG revealed minimum muscular electrophysiologic activity, probably due to muscle underlying the patch. The HDAM we employed was thus not able to produce reconstruction of the skeletal muscle, and was progressively remodeled into fibrous tissue. Since the ultimate reason for failure of muscle regeneration is a lack of myogenesis, future studies will use ACMs preconditioned by various regulators of myoblast proliferation and differentiation.

Central venous access in pediatric patients.

Occlusion of traditional sites for central venous cannulation is a challenging problem in patients that require a permanent central venous line for chronic administration of nutrients or drugs. In rare cases, extensive central venous thrombosis of the superior and inferior vena cava may preclude catheterization, and uncommon routes should be used. We describe our approach for placement of chronic central venous lines in two pediatric patients with short bowel syndrome and extensive caval occlusion.

Cervical spinal epidural abscesses. A report on five cases.

The authors report a series of five cases of non tuberculous cervical spinal epidural abscesses. There were neither patients suffering from immunodeficiency syndromes nor drug addicts; all the patients were in their seventh decade; two patients were affected by diabetes mellitus refractory to medical treatment. Retropharyngeal abscess was the main etiological risk factor (two cases); Staphylococcus aureus was cultured in two cases. Gadolinium MRI was necessary for a preoperative diagnosis, planning surgical approach and postoperative prognosis. Surgical debridement was performed via an anterior approach in those cases where the collection was located lower than C4 and did not span more than three vertebral segments; posterior approach, via a laminectomy, was performed in a case of C1-C2 location of the lesion and in a case of involvement of the whole cervical spine. Surgical results were poor in those patients affected by diabetes mellitus, a lesion involving the high cervical segments (higher than C4) or a lesion spanning more than three levels. Medical treatment with MRI follow-up was not undertaken in any of the patients and we opted for surgical drainage in all the cases due to the possibility of a sudden neurological deterioration, caused both by spinal cord mechanical compression and vascular compromission.

Analgesia and sedation in the critically ill--a practical approach.

Advancements in intensive care therapy have progressed rapidly over the last two decades. Associated with this have been scientifically unsubstantiated sedation and analgesia practices in the intensive care unit. There is little consensus as to which agents are the most suitable, let alone when and how to use them. There are few, if any, placebo-controlled trials involving sedative drugs in critically ill patients. In an analysis of the literature, we have attempted to present a practical approach to sedation and analgesia practices in the critically ill patient. The aim is to present a framework upon which medical personnel managing critically ill patients can develop a strategy for their own circumstances.

Critical care research and pre-emptive informed consent: a practical approach used in Chris Hani Baragwanath ICU.

OBJECTIVES: 1) To establish a protocol within international and local ethical guidelines to obtain informed consent for critical care research, overcoming constraints previously described and 2) To evaluate eventual recruitment using this protocol. DESIGN: Prospective descriptive study. SETTING: Multidisciplinary ICU in a community-based university teaching hospital. PATIENTS AND PARTICIPANTS: Following approval by the University Ethics Committee and Hospital Review Board, patients admitted between January and May 1996 were assessed on weekdays for potential enrollment into existing clinical trials. Discussion with potential candidates and/or next-of-kin occurred at the earliest opportunity and informed consent was obtained preemptively. Next-of-kin was notified if enrollment subsequently occurred. We evaluated the number of patients screened, the number of potential study candidates, the number for whom consent was obtained or refused and the number subsequently enrolled. INTERVENTIONS: None RESULTS: Of 249 patients screened, 149 (60%) did not meet the inclusion criteria. Of 100 potential study candidates (40% of all patients screened), we failed to make contact with the next-of-kin in 29 cases (12% of all patients screened). Thus 71 patients or next-of-kin were counselled (28% of all patients screened). In all, 30 patients (12% of all patients screened) were subsequently enrolled into a study. CONCLUSIONS: A policy of pre-emptive informed consent enabled us to overcome some of the problems previously experienced in our unit with regards to patient enrollment in critical care research. Although overall recruitment remained low, predictions for future enrollment can be made from this study.

Basal and forskolin-stimulated cyclic adenosine monophosphate in intact human platelets during the menstrual cycle.

In previous studies we observed modifications of cyclic adenosine monophosphate and adenylate cyclase activity in human endometrium during the menstrual cycle. In the present study our intension was to verify whether these modifications occur in isolated intact platelets. The results demonstrate that in nine normal women platelet cyclic adenosine monophosphate content varies during the menstrual cycle both in basal and in stimulated conditions (in vitro addition of forskolin). In fact, significantly higher levels of cyclic adenosine monophosphate were consistently observed during the proliferative phase. These findings provide evidence that platelet cyclic adenosine monophosphate metabolism normally varies during the menstrual cycle, which suggests a possible involvement of this system in some important clinical events.