OUTCOMES OF A LONG-TERMS MICROVASCULAR TRAINING FOR RESIDENTS IN ORTHOPEDIC.

The acquisition of specific technical skills in the field of microsurgery like the use of operating microscope and microsurgical instruments, arterial and venous anastomosis, vascular grafts, nerve sutures and tenorrhaphies, is very important during the training in Orthopedics and in Hand Surgery in order to deal with management of complex and amputative traumas of the upper limb. The learning curve in microsurgical techniques is significantly shortened for surgeons who benefit from pre-clinical courses on an animal model. The aim of this study was to standardize a long-term microsurgical activity during the training in Orthopedics and Hand Surgery and to document the benefits that the residents of the School of Specialization got by chance of practicing weekly this discipline on in-vivo model. In 2016, a protocol for teaching in vivo microsurgery on Wistar rats for orthopedics and hand surgery residents was approved. In the first 3 years of graduation course, the students performed the training aimed at acquiring manual dexterity and confidence with the microsurgical instrumentations on nonliving models. Subsequent exercises were performed ex vivo on chicken leg models under the microscope or loupes. Finally, the in-vivo rat exercises were intended for residents in the last 2 years who required access to the supplementary diploma in hand surgery. Outcome evaluations consisted of the Global Rating Scale score and time to completion. Two-tailed Student t test was performed to compare initial and final outcome evaluations (p<0.05). Only 8 residents completed the microvascular training of almost thirty microsurgical teaching sessions administered on a weekly basis. The total mean GRS score (and standard deviation) improved from 15±2 points for the initial score to 21±6 points for the final score (p<0.005). Time to completion of the anastomosis also significantly improved (p<0.005), from a mean score of 31:18±9:21 minutes for the initial time to 21:15±6:10 minutes for the final time. A microvascular training curriculum utilizing a live rat model, preceded by a training on non-living models, provides a superior surgical simulation experience and is effective at improving resident microvascular surgical skills.

Sleep/wake rhythm modifications in the Italian population during SARS-CoV2 pandemic: a web-based cross-sectional survey.

OBJECTIVE: The study aims to investigate in a representative sample of the Italian population whether the SARS-CoV2 pandemic and the subsequent home isolation had repercussion on the daily sleep/wake cycling and habits. MATERIALS AND METHODS: A web-based cross-sectional survey consisted of various multiple-choice questions concerning demographic characteristics, sleep habits, and sleep-related problems was broadcast through mainstream social-media. Individuals were randomly allowed to participate from April 29th to May 17th, namely 50 days after the lockdown imposition and the day before its abrogation. RESULTS: 58.84% of respondents experienced a change in their sleep habits. 71% of those whose sleep changed showed a delayed sleep pattern. Overall, a two-fold risk of delayed sleep pattern without any change in total sleep time emerged during the investigation period. Females emerged almost 2 times more likely to modify their sleep habits than males. Youths were also more likely to experience modifications than old people, who conversely appeared protected. A significant improvement in daytime sleepiness occurred during the home isolation which additionally correlated with delayed bedtime and less sleep time. CONCLUSIONS: A high rate of change in sleep habits, especially among youths and females, occurred in Italian population during the home isolation to limit the SARS-CoV2 pandemic. Moreover, self-reported daytime sleepiness decreased in severity.

Improved percent-predicted peak VO2 is associated with lower risk of hospitalization in patients with coronary heart disease. Analysis from the FRIEND registry.

BACKGROUND: Normal standards for peak oxygen consumption (VO2peak) are controversial because they tend to be population and protocol specific. This study was undertaken to examine the association between percentage of age-predicted VO2peak and all-cause hospital readmission in cardiac outpatients who were referred to an exercise-based secondary prevention program. METHODS: Hospital readmission was assessed in 1283 male patients with coronary heart disease (CHD) three years after enrolment, and related to the age-predicted VO2peak derived from the Fitness Registry and the Importance of Exercise: A National Data Base equation (FRIEND%PRED). VO2peak was estimated using a moderate perceptually regulated 1-km treadmill-walking test. Readmission was also assessed during the fourth-to-sixth years as function of improvement in FRIEND%PRED in 845 patients who were re-evaluated 3 years after baseline. RESULTS: During the 3-years after baseline, readmission rate was lower across increasing tertiles of FRIEND%PRED. Compared to the lowest tertile, the adjusted hazard ratios (HRs) for the second and third tertile were 0.98 (95% CI 0.76-1.27, p = 0.90) and 0.71 (0.53-0.95, p = 0.002). The rate of readmission from the fourth-to-sixth years after baseline was lower across tertiles of improved FRIEND%PRED, with adjusted HRs 0.78 (0.60-1.03, p = 0.08) and 0.58 (0.42-0.75, p < 0.0001) for the intermediate and high tertiles vs the lowest tertile. After adjustment for confounders, every 1 unit % increase in FRIEND%PRED was associated with a 3% reduction in risk of readmission (HR 0.97, 0.95-0.98, p < 0.0001). CONCLUSIONS: Age-predicted VO2peak estimated by a moderate treadmill-walk predicts hospital readmission in outpatients with CHD undergoing secondary prevention.

Treatment of carpal tunnel syndrome with alpha-lipoic acid.

Carpal Tunnel Syndrome (CTS) is the most common peripheral mononeuropathy; its symptoms and functional limitations significantly penalize the daily activities and quality of life of many people. While surgery is reserved to most severe cases, the earlier stages of disease may be controlled by a pharmacological treatment aimed to "neuroprotection", i.e. to limiting and correcting the nerve damage. Our study was aimed to compare the efficacy of a fixed association of alpha-lipoic acid (ALA) 600 mg/die and gamma-linolenic acid (GLA) 360 mg/die, and a multivitamin B preparation (Vit B6 150 mg, Vit B1 100 mg, Vit B12 500 microg daily) for 90 days in 112 subjects with moderately severe CTS. Demographic, case-history and treatment efficacy data were collected; the Boston questionnaire was administered and the patients were evaluated by Hi-Ob scale and electro-myography. A significant reduction in both symptoms scores and functional impairment (Boston questionnaire) was observed in ALA/GLA group, while the multivitamin group experienced a slight improvement of symptoms and a deterioration of functional scores. Electromyography showed a statistically significant improvement with ALA/GLA, but not with the multivitamin product. The Hi-Ob scale showed significant efficacy of ALA/GLA in improving symptoms and functional impairment, while in the multivitamin group the improvement was significant, but less marked than in the ALA/GLA group. In conclusion, the fixed association of ALA and GLA proved to be a useful tool and may be proposed for controlling symptoms and improving the evolution of CTS, especially in the earlier stages of disease.

Effects of elevating the head of bed on interface pressure in volunteers.

OBJECTIVE: Intensive care unit patients are at particular risk for pressure ulcers and ventilator-associated pneumonia. Current guidelines recommend that mechanically ventilated patients be kept in a semirecumbent position with the head of bed elevated 30 degrees -45 degrees to prevent aspiration and ventilator-associated pneumonia. We tested the effects of elevating the head of bed on the interface pressure between the skin of the sacral area and the bed with healthy volunteers. INTERVENTIONS: Interface pressure profiles of the sacral area were obtained for the 0 degrees , 10 degrees , 20 degrees , 30 degrees , 45 degrees , 60 degrees , and 75 degrees head of bed elevated positions from 15 subjects (14 men, one woman). MEASUREMENTS AND MAIN RESULTS: Peak sacral interface pressures increased with large increases in head of bed elevation. The 30 degrees , 45 degrees , 60 degrees , and 75 degrees head of bed positions all had peak interface pressures that were significantly (p < 0.02) greater than the supine measurement and also were different from all other head of bed positions. Affected areas, defined as areas over which an interface pressure >or=32 mm Hg was obtained, increased with large elevation of the head of bed. The affected areas of the 45 degrees , 60 degrees , and 75 degrees head of bed positions were significantly greater than the supine position and were also significantly different from all other head of bed positions. CONCLUSIONS: Raising the head of bed to 30 degrees or higher on a intensive care unit bed increases the peak interface pressure between the skin at the sacral area and support surface in healthy volunteers. At 45 degrees head of bed elevation or higher, the affected area attributed to a skin-intensive care unit bed interface pressure >or=32 mm Hg increased as well. Further study is needed to determine whether the increased peak interface pressures and affected areas that result from raising the head of bed actually increase the incidence of pressure ulcer formation.

A study about mechanisms of des-gamma-carboxy prothrombin's production in hepatocellular carcinoma.

AIM: Des-gamma-carboxy prothrombin (DCP) is an abnormal prothrombin, increased in serum of patients with hepatocellular carcinoma (HCC) as result of an acquired defect of post-translational carboxylation of prothrombin's precursor. It is unclear if the reduced activity of gamma-carboxylase is secondary to vitamin K deficiency or to an altered gene encoding this enzyme. The aim of this study was to evaluate the effect of vitamin K administration on DCP and alpha-fetoprotein (AFP) levels, to identify a relationship between vitamin K and DCP serum levels and to investigate mechanisms of serum elevation of DCP levels. METHODS: The authors determined DCP and AFP serum levels and vitamin K concentration in 64 cirrhotics with HCC and in 60 cirrhotic subjects without HCC. In HCC subjects DCP and AFP levels were measured before and after vitamin K administration. A t-test for unpaired data was applied (P values <0.05 statistically significant). RESULTS: Only HCC patients had detectable levels of DCP and significant AFP levels. Administration of vitamin K reduced DCP but not AFP levels in HCC patients. No correlation was observed between vitamin K concentration and DCP levels: vitamin K concentration was similar both in HCC patients and in control group without HCC; HCC patients had the same vitamin K concentration regardless of elevated o reduced DCP levels after vitamin K administration. CONCLUSION: DCP detectable serum levels are the result not only of vitamin K deficiency or selective defects of carboxylase, because probably alterations of membrane receptors or cytoplasmatic transfers, that are necessary for the function of vitamin K, are involved.

Clinical and endoscopic presentation of primary gastric lymphoma: a multicentre study.

BACKGROUND: Although the stomach is the most frequent site of intestinal lymphomas, few data are available on both clinical endoscopic presentation of gastric lymphoma and possible differences between low-grade and high-grade lymphomas. METHODS: Clinical, histological and endoscopic records of consecutive patients with primary low-grade or high-grade lymphoma diagnosed were retrieved. Symptoms were categorized as 'alarm' or 'not alarm'. The endoscopic findings were classified as 'normal' or 'abnormal'. RESULTS: Overall, 144 patients with primary gastric lymphoma were detected, including 74 low-grade and 70 high-grade lymphoma. Alarm symptoms, particularly persistent vomiting and weight loss, were more frequently present in patients with high-grade lymphoma than in those with low-grade lymphoma (54% vs. 28%; P = 0.002). Low-grade lymphomas presented as 'normal' appearing mucosa (20% vs. 0%; P = 0.0004) or petechial haemorrhage in the fundus (9% vs. 0%; P = 0.02) more frequently than high-grade lymphomas, being also more often confined to the antrum (47% vs. 27%, P = 0.03) and associated with Helicobacter pylori infection (88% vs. 52%, P < 0.0001). On the contrary, high-grade lymphomas presented more commonly as ulcerative type (70% vs. 52%; P = 0.03), being also more frequently diagnosed in stage >I when compared with low-grade lymphomas (70% vs. 21%, P < 0.0001). CONCLUSIONS: The overall prevalence of alarm symptoms is quite low and may be absent in more than 70% of patients with low-grade lymphoma.

[Heterozygosis H63D in patients with steatohepatitis and chronic hepatitis C]. / Eterozigosi H63D per emocromatosi in pazienti affetti da steatoepatite e epatite cronica da virus C.

OBJECTIVE: Classic hereditary hemochromatosis is an autosomal recessive iron-overload disorder associated with mutation of the HFE gene. The homozygous genetic defect predisposes to a chain of events that may culminate in severe damage in multiple organs. Pathologic implications of heterozygous defect are still questionable; in fact since these individuals may have slight increases in intra-cellular iron, it has been questioned whether this would enhance damage from other diseases. We investigated whether steatohepatitis and chronic hepatitis C can be worsened by heterozygosis for C282Y and H63D. PATIENTS AND METHODS: We investigated 216 subjects with Steatohepatitis and/or chronic hepatitis C diagnosed by ultrasonography and liver biopsy with histological assessment compared with 110 healthy subjects. In all subjects we performed Saturated Transferrine, Plasma Ferritin and the research of HFE mutation by a Real Time Method. A statistical analysis was performed. RESULTS: A H63D mutation was present in 32/108 patients with Steatohepatitis, in 30/108 patients with chronic hepatitis C and in 22/110 healthy subjects. A C282Y mutation was present in 2/108 patients with chronic hepatitis C, in 4/108 with steatohepatitis and in 2/108 healthy subjects. No significant difference was present about incidence of this mutation between pathological and healthy subjects. No significant differences have observed between pathological groups and normal group about the degree of histological damage. CONCLUSIONS: Our study revealed that steatohepatitis and chronic hepatitis C cannot be worsened by heterozygosis for C282Y and H63D.

CREB-binding protein and p300/CBP-associated factor are transcriptional coactivators of the p53 tumor suppressor protein.

The structurally related transcriptional coactivators p300 and CBP possess histone acetyltransferase activity and associate with P/CAF, which is also a histone acetyltransferase. CBP and p300 have properties of tumor suppressor proteins; their interaction with P/CAF is disrupted by the adenoviral E1A oncoprotein, and the genes encoding CBP and p300 are mutated in human cancer. We observed a physical interaction between the transactivation domain of the p53 tumor suppressor protein and CBP. Furthermore, CBP and P/CAF enhanced the ability of p53 to activate expression of the endogenous p21(cip1/waf1) gene, whereas E1A and dominant negative CBP mutants suppressed p53-dependent p21(cip1/waf1) expression. These studies link two tumor suppressor families and provide a framework for understanding the molecular mechanism by which p53 activates transcription.

[Benign thyroid nodule: what is the treatment? Personal experience]. / Tireopatia nodulare benigna: quale trattamento terapeutico? Esperienza personale.

INTRODUCTION: Solitary thyroid nodule is an important pathology with an incidence of 2-5% in the Italian population. The diagnosis was based on clinical exam, laboratory tests and ultrasonographic evaluation. MATERIALS AND METHODS: The study undertook has the purpose to assess the usefulness between lobe-isthmusectomy (with corresponding risk of possible relapse and complications for reintervention) and total thyroidectomy (with corresponding post-surgical treatment complications), for benign thyroid disease with solitary nodule, on selected cases for disease and corresponding risk factors, in the retrospective clinical study, using laboratory tests and ultrasonographic evaluation. The study was conducted on 80 patients admitted from 1994 to 2000 with diagnosis of benign thyroid nodule and operated with lobe-isthmusectomy. In seven patients the operation had to be converted in total thyroidectomy. RESULTS: Operative mortality was nil and long-term results at a mean follow-up of three years are encouraging. DISCUSSION: The main advantages of lobe-isthmusectomy for benign solitary thyroid nodule consist in less postoperative complications and less hospital stay. CONCLUSIONS: Therefore our experience has carried us to consider the lobectomy which treatment of choice for all those benign thyroid diseases with solitary nodule.

Change in oligomerization specificity of the p53 tetramerization domain by hydrophobic amino acid substitutions.

The tumor suppressor function of the wild-type p53 protein is transdominantly inhibited by tumor-derived mutant p53 proteins. Such transdominant inhibition limits the prospects for gene therapy approaches that aim to introduce wild-type p53 into cancer cells. The molecular mechanism for transdominant inhibition involves sequestration of wild-type p53 subunits into inactive wild-type/mutant hetero-tetramers. Thus, p53 proteins, whose oligomerization specificity is altered so they cannot interact with tumor-derived mutant p53, would escape transdominant inhibition. Aided by the known three-dimensional structure of the p53 tetramerization domain and by trial and error we designed a novel domain with seven amino acid substitutions in the hydrophobic core. A full-length p53 protein bearing this novel domain formed homo-tetramers and had tumor suppressor function, but did not hetero-oligomerize with tumor-derived mutant p53 and resisted transdominant inhibition. Thus, hydrophobic core residues influence the oligomerization specificity of the p53 tetramerization domain.

A prospective study of depression and immune dysregulation in multiple sclerosis.

This study examined psychologic distress and immune function in patients with chronic-progressive multiple sclerosis participating in a placebo-control trial of cyclosporine. Immune measures included percentages and absolute numbers of CD2+, CD4+, CD8+, Leu-11-b+, HLA-DR (IA+), and transferrin-receptor-positive cells, which were evaluated by immunofluorescence using monoclonal antibodies. Distress was measured with self-report scales. The Expanded Disability Status Scale assessed neurologic disability. Subjects were followed up for 2 years, and their high-depressed and low-depressed times were compared. Times of greater depression were associated with lower CD8+ cell numbers and CD8+%, and a higher CD4/CD8 ratio. CD4+ cell numbers and percent were also higher when subjects were depressed, but only in the placebo group. There were no differences in Expanded Disability Status Scale when subjects were more depressed. Evaluation of a single subject revealed that Ia+ and transferrin-receptor-positive lymphocytes increased 3 months before distress increased. It was concluded that distress is associated with immune dysregulation in multiple sclerosis, although the mechanisms of this association have yet to be delineated.

What can we do to improve physical function in older persons with type 2 diabetes?

BACKGROUND: Older persons with type 2 diabetes are at higher risk for functional impairment than are their age-matched counterparts without-diabetes. We therefore sought to identify factors associated with impaired physical function in older persons with type 2 diabetes by using a cross-sectional study design. METHODS: We studied 1238 persons with type 2 diabetes who were 55 years of age or older and enrolled in the Type II Diabetes Patient Outcomes Research Team (PORT) project. Subjects were primary care patients at a large staff model health maintenance organization who had completed a mailed survey that collected information about demographics (age, race, marital status, income, education, gender, and body mass index [BMI]), health behaviors (exercise, smoking, and alcohol), care and control of diabetes (therapy, self-reported glucose control, home glucose monitoring, and disease duration), mood (Center for Epidemiologic Studies--Depression Scale [CES-D]), comorbidity, and the Short-Form-36 health survey (SF-36). We evaluated the bivariate relationships between the PFI- 10, a 10-item measure of physical function from the SF-36, and candidate independent variables from the domains described previously. Variables that were significant at an a level of .10 were entered into a multiple linear regression model. RESULTS: There were eight independent predictors of impaired physical function (all p < .05, R2 = .40). Factors associated with impaired function in order of their relative importance were as follows: a higher comorbidity score, older age, obesity, lack of regular exercise, CES-D score higher than 20, taking insulin, lower formal education, and abstinence from alcohol. CONCLUSIONS: Increased comorbidity and older age are associated with poorer function, as is the severity of diabetes and less formal education. Exercise, lower BMI, and better mood are associated with better function. Therefore, promoting regular exercise and weight loss, in addition to treating depression, are likely to preserve or even improve the functional status of older persons with type 2 diabetes. Moderate alcohol use may be beneficial as well. The extent to which these relationships persist in prospective studies or clinical trials remains to be evaluated.

Comparing the effectiveness of behavioral treatment for chemotherapy-induced nausea and vomiting when administered by oncologists, oncology nurses, and clinical psychologists.

Adequate control of side effects during medical treatment of cancer increases patient compliance and quality of life. Antiemetic drugs are not an effective treatment for the one in three cancer patients on chemotherapy who experience anticipatory nausea and vomiting (ANV); the behavioral treatment of systematic desensitization has been found effective for ANV when delivered by clinical psychologists. This study examined the effectiveness of systematic desensitization when delivered by medical personnel versus clinical psychologists. Seventy-two consecutive cancer patients with ANV were randomly assigned to no-treatment control or to systematic desensitization from 5 behaviorally trained clinical psychologists, 6 clinical oncologists, or 10 oncology nurses. The treatment was found effective in reducing anticipatory nausea, anticipatory vomiting, posttreatment nausea, and posttreatment vomiting compared to control patients, with no significant differences in effectiveness found between clinical psychologists and oncology staff. Although medical personnel should not engage patients in psychotherapy or other interventions that cannot be completed successfully, they can treat patients effectively with systematic desensitization and should be encouraged to learn and use this and other behavioral intervention techniques to benefit total patient care.

A behavioral perspective on insomnia treatment.

The major behavioral treatments of insomnia--progressive relaxation, biofeedback, cognitive approaches, stimulus control instructions, chronotherapy, and sleep restriction therapy--are described. The basis of these interventions are conceptualized as issuing from the interdependence of sleep and wakefulness, the temporal organization of sleep-wake processes, cognitive effects on arousal, the role of perpetuating factors in chronic insomnia, and conditioning. A pilot study of the conditioning of rapid sleep onset with the aid of a hypnotic provides a preliminary demonstration of the application of conditioning to the pharmacotherapy of sleep. It is predicted that the commonly accepted view of sleep latency as solely reflecting physiological sleep tendency, will require modification to include the effects of conditioning. The current pattern of hypnotic usage, an issue of widespread concern, is subjected to a behavioral analysis based on a new model of conditioned tolerance. The intermittent administration of placebo within a hypnotic regimen is predicted to be especially beneficial in sustaining hypnotic efficacy.

Stress, Multiple Sclerosis, and Everyday FunctioningA Review of the Literature with Implications for Intervention.

Numerous studies have described an association between stress and the onset or exacerbation of multiple sclerosis (MS). Most of the studies that have been conducted to date, however, have had methodological flaws including: (1) retrospective designs, (2) inadequate or absent control groups, (3) small sample sizes, (4) clinical measures that are insensitive to underlying disease activity, and (5) wide variation in the measurement of stress. Animal models of MS have enabled researchers to examine the effects of stress directly in the central nervous system. Stress affects three biological systems that may be dysregulated in MS: the neuroendocrine system, the sympathetic nervous system, and the serotonergic neurotransmitter system. Future stress-MS research should evaluate the relationship between stress and these systems.

Postoperative acute renal failure secondary to rhabdomyolysis from exaggerated lithotomy position.

Perioperative renal dysfunction is a common problem following urogenital surgery. The most common causes of renal failure include ischemic or nephrotoxic acute tubular necrosis, renal vascular injury, and urinary tract obstruction. This case conference describes a patient who developed acute renal failure, secondary to rhabdomyolysis after a 7-hour urologic surgical procedure in an exaggerated lithotomy position. Early diagnosis and aggressive treatment are essential to prevent or limit the severity of acute renal failure. A review of the literature and pathophysiology of acute renal failure secondary to rhabdomyolysis is included.

Myocardial ischemia detected by transesophageal echocardiography in a patient undergoing peripheral vascular surgery.

Prevention and early treatment of myocardial ischemia remain among the primary goals of the anesthesiologist taking care of high-risk patients, such as those undergoing vascular surgery. Guidelines have been published to assist in directing preoperative evaluation and optimization of cardiovascular status. Although perioperative monitoring allows early detection of ischemic events, all monitors have limitations that must be understood before they can be used effectively. We present a case of severe intraoperative myocardial dysfunction detected only by transesophageal echocardiography in a patient undergoing a peripheral vascular procedure. Preoperative and intraoperative management is also discussed.

Early recognition of acute cardiovascular beriberi by interpretation of hemodynamics.

Acute fulminant cardiovascular beriberi is an acute thiamine deficiency, which, if not recognized and treated, can lead to high cardiac output failure and death. The symptoms of acute thiamine deficiency include severe lactacidemia, and the presence of a high cardiac output and extremely low oxygen consumption in a patient who is hemodynamically stable. In this case conference, we describe a patient who was diagnosed with acute cardiovascular beriberi.