Radioactive seed localization is a safe and effective tool for breast cancer surgery: an evaluation of over 25,000 cases.

Radioactive seed localization (RSL) provides a precise and efficient method for removing non-palpable breast lesions. It has proven to be a valuable addition to breast surgery, improving perioperative logistics and patient satisfaction. This retrospective review examines the lessons learned from a high-volume cancer center's RSL program after 10 years of practice and over 25 000 cases. We provide an updated model for assessing the patient's radiation dose from RSL seed implantation and demonstrate the safety of RSL to staff members. Additionally, we emphasize the importance of various aspects of presurgical evaluation, surgical techniques, post-surgical management, and regulatory compliance for a successful RSL program. Notably, the program has reduced radiation exposure for patients and medical staff.

Clinical efficacy of sequential treatments in KRASG12C-mutant metastatic colorectal cancer: findings from a real-life multicenter Italian study (CRC-KR GOIM).

BACKGROUND: The presence of KRASG12C mutation in metastatic colorectal cancer (mCRC) correlates with poor outcome. Although different selective inhibitors are under clinical development, the optimal treatment remains uncertain. Thus, we conducted a retrospective analysis in a large cohort of patients with KRASG12C mCRC treated in 12 Italian oncology units. PATIENTS AND METHODS: Patients with unresectable mCRC harboring KRASG12C mutation receiving a first-line chemotherapy doublet or triplet between 2011 and 2021 were included in the study. Evaluation of overall response rate (ORR), progression-free survival (PFS) and overall survival (OS) analysis was carried out. RESULTS: A total of 256/6952 (3.7%) patients with mCRC displayed KRASG12C mutation; of these, 111 met the inclusion criteria. The ORR of first-line therapy was 38.7% (43/111). Median PFS (mPFS) was 9 months [95% confidence interval (CI) 7.5-10.5 months]. After progression, only 62% and 36% of the patients are fit to receive second or third lines of treatment, with limited clinical benefit. Median OS (mOS) was 21 months (95% CI 17.4-24.6 months). In patients receiving first-line triplet chemotherapy, ORR was 56.3% (9/16), mPFS was 13 months (95% CI 10.3-15.7 months) and mOS was 32 months (95% CI 7.7-56.3 months). For irinotecan-based doublets, ORR was 34.5 (10/29), mPFS was 9 months (95% CI 6.4-11.6 months) and mOS was 22 months (95% CI 16.0-28.0 months). With oxaliplatin-based doublets ORR was 36.4% (24/62), mPFS was 7 months (95% CI 4.6-9.4 months) and mOS was 18 months (95% CI, 13.6-22.4 months). CONCLUSION: Patients with KRASG12C-mutant mCRC had a disappointing response to standard treatments. Within the limitations of a retrospective study, these results suggest that first-line chemotherapy intensification with FOLFOXIRI is a valid option in fit patients.

Motor phenotype is not associated with vascular dysfunction in symptomatic Huntington's disease transgenic R6/2 (160 CAG) mice.

Whereas Huntington's disease (HD) is unequivocally a neurological disorder, a critical mass of emerging studies highlights the occurrence of peripheral pathology like cardiovascular defects in both animal models and humans. The overt impairment in cardiac function is normally expected to be associated with peripheral vascular dysfunction, however whether this assumption is reasonable or not in HD is still unknown. In this study we functionally characterized the vascular system in R6/2 mouse model (line 160 CAG), which recapitulates several features of human pathology including cardiac disease. Vascular reactivity in different arterial districts was determined by wire myography in symptomatic R6/2 mice and age-matched wild type (WT) littermates. Disease stage was assessed by using well-validated behavioural tests like rotarod and horizontal ladder task. Surprisingly, no signs of vascular dysfunction were detectable in symptomatic mice and no link with motor phenotype was found.

Malignant pheochromocytoma and paraganglioma: future considerations for therapy.

Pheochromocytoma and paraganglioma are rare neuroendocrine tumors. Knowledge about such neoplasms ameliorated in the last 10-15 years with the discovery of increasing number of germ line mutations even in apparently sporadic cases. Seemingly, genetic tests are going to be an integral part of diagnostic procedures. Standard therapies (advanced surgery, radiometabolic therapy, chemotherapy and radiotherapy) have revealed suboptimal results in tumor size reduction and survival. Currently, there is no standard therapeutic protocol and thus some patients end up with overtreatment while others are undertreated. An effective molecular target therapy aiming at permanent control of these highly complex neoplasms should be the aim of future efforts. In clinical setting investigatory trials with multiple drug therapies targeting a variety of different parallel pathways should be available. Successful management requires a multidisciplinary teamwork.

Links between metabolic syndrome and cardiovascular autonomic dysfunction.

BACKGROUND: Type 2 diabetes (T2D) might occur within metabolic syndrome (MbS). One of the complications of T2D is an impaired (imp) cardiovascular autonomic function (CAF). AIMS: In subjects with T2D and age ≤ 55 years, the prevalence of impCAF and its relationship with BMI, waist, HbA(1c) values, MbS, hypertension, and family history of T2D and/or hypertension were analysed. METHODS: 180 subjects consecutively undergoing a day hospital for T2D were studied. The IDF criteria were used to diagnose MbS. To detect impCAF, 5 tests for the evaluation of CAF were performed with Cardionomic (Meteda, Italy). Univariate and multivariate analyses were performed. RESULTS: The prevalence of impCAF and MbS were 33.9% and 67.8%, respectively. Among diabetics with impCAF, 86.9% had MbS. ImpCAF was significantly associated with MbS, overweight, and HbA(1c) > 7%. Both logistic (P = 0.0009) and Poisson (P = 0.0113) models showed a positive association between impCAF and MbS. The degree of ImpCAF showed a positive linear correlation with BMI and HbA(1c) values. CONCLUSIONS: The study demonstrates that glycaemic control and overweight influence CAF and that T2D + MbS is more strongly associated with impCAF than isolated T2D. We suggest that MbS not only increases the cardiovascular risk of relatively young subjects with T2D but is also associated with impCAF.

Nateglinide provides tighter glycaemic control than glyburide in patients with Type 2 diabetes with prevalent postprandial hyperglycaemia.

AIMS: Postprandial hyperglycaemia in patients with Type 2 diabetes mellitus has been linked to the development of cardiovascular disease. This study compared the effects of mealtime (thrice-daily) nateglinide with once-daily glyburide on postprandial glucose levels in patients with Type 2 diabetes and postprandial hyperglycaemia. METHODS: Patients with Type 2 diabetes aged ≥ 21 years with 2-h postprandial glucose levels ≥ 11.1 mmol/l, HbA(1c) of 6.5-8.5% (48-69 mmol/mol) and BMI of 22-30 kg/m(2) were randomized to 6 weeks' double-blind treatment with nateglinide 120 mg three times daily prior to meals, or glyburide 5 mg once daily before breakfast. The primary endpoint was the baseline-adjusted change in plasma glucose from preprandial (fasting plasma glucose) to 2-h postprandial glucose levels (2-h postprandial glucose excursion) at 6 weeks. RESULTS: Patients were randomized to nateglinide (n = 122) or glyburide (n = 110). The treatment groups were similar in terms of age, gender, BMI, fasting plasma glucose, 2-h postprandial glucose and HbA(1c). At endpoint, nateglinide recipients had significantly greater reductions than those receiving glyburide in both the 2-h (-2.4 vs. -1.6 mmol/l; P = 0.02) and 1-h (-1.7 vs. -0.9 mmol/l; P = 0.016) postprandial glucose excursions. Adverse events, most commonly symptomatic hypoglycaemia, were reported in 26% of recipients of glyburide and 22% of recipients of nateglinide. Episodes of suspected mild hypoglycaemia were reported in 24% of recipients of glyburide and 10% of recipients of nateglinide. CONCLUSIONS: Nateglinide leads to greater reductions in postprandial glucose excursions and is associated with a lower risk of hypoglycaemia than glyburide in this selected population of patients with Type 2 diabetes.

Preprandial combination of lispro and NPH insulin improves overall blood glucose control in type 1 diabetic patients: a multicenter randomized crossover trial.

BACKGROUND AND AIM: While lispro insulin has been reported to lower postprandial blood glucose concentrations, less consistent effects have been shown for glycosylated hemoglobin (HbA1c) levels. Aim of this study was to determine whether pre-meal association of NPH, an intermediate-acting insulin, with lispro improves overall glycemic control in type 1 diabetic patients. METHODS AND RESULTS: Eighty-five type 1 diabetic patients were studied in a multicenter randomized comparative (human regular vs lispro insulin) crossover (3-month) study in which NPH insulin was given as a dinner or bedtime injection and at breakfast and lunch if necessary. The number of injections was kept constant: 42% and 58% of patients injected insulin 3 and 4 times per day, respectively. Fasting and preprandial blood glucose levels were similar, while postprandial levels improved after lispro compared to human regular insulin (breakfast: 8.28 +/- 2.39 vs 9.28 +/- 2.72 mmol/l; lunch: 8.33 +/- 2.67 vs 9.06 +/- 2.67 mmol/l, dinner: 8.06 +/- 2.72 vs 9.28 +/- 2.44 mmol/l, ANOVA: p = 0.003). HbA1c also improved after lispro: 8.1 +/- 0.9 vs 8.3 +/- 0.8%, p < 0.05. The rate of hypoglycemia was similar. Patients showed better acceptance of lispro treatment (p < 0.001). CONCLUSIONS: Lispro improves overall blood glucose control in type 1 diabetic patients without increasing the incidence of hypoglycemia. This can be achieved by an optimal combination of lispro insulin with NPH whenever the time intervals between meals are too long.

[S(-) bupivacaine (levobupivacaine) in peripheral blocks: preliminary results]. / S(-) bupivacaina (levobupivacaina) nei blocchi periferici: risultati prelminari.

We have compared the onset time, anesthetic potency and adverse effects of three local anaesthetics (ropivacaine, levobupivacaine and bupivacaine) in two type of peripheral blocks (brachial plexus block for upper limb and femoral nerve block for lower limb) in adult patients in a double blind, randomized, prospective study. A total of 66 patients undergoing orthopaedic surgery were randomly allocated to receive brachial plexus block or femoral nerve blockade with 0,5% ropivacaine (group R, n=22), 0,5% levobupivacaine (group L, n=22) or 0,5% bupivacaine (group B, n=22), each groups has been divided into two subgroups (LBP n=11, RBP n=11, BPB n=11, LBF n=11, RBF n=11, BBF n=11) dipending on the type of block. The onset of sensory nerve block was similar for the three groups; the onset of motor block and onset time ready to surgery were faster in group R (-30%) if compared with group L and B. The duration of motor block and sensory block was respectively longer in group L and in group B. Study results have not been influenced by the blocks, except for plexus nerve block where we observed the same results for group B and group R in relation to onset time ready to surgery. VRS scores were higher in group R as showed by the number of analgesic request in postoperative period. We did not observe any adverse effect. We conclude that ropivacaine acts faster with less interpatient variability, while levobupivacaine and bupivacaine offer a prolonged postoperative analgesia. For this reason, with the exception of bupivacaine due to major cardio and neuro toxicity, we can indifferently use levobupivacaine or ropivacaine depending on the requested characteristics of the anesthetic.

Reducing perioperative blood loss in patients undergoing total hip arthroplasty.

In this prospective, randomised, double-blind study, we investigated the effect of epidural anaesthesia and an antifibrinolytic agent, Aprotinin (500,000 KIU in bolus before surgery and 500,000 KIU h(-1) in drip form during surgery), on intra and postoperative blood loss and transfusion requirements in total hip arthroplasty. Sixty patients were allocated randomly to four groups (A: epidural + general anesthesia + Aprotinin, B: epidural + general anesthesia + placebo (equal volume), C: general anaesthesia + Aprotinin, D: general anaesthesia + placebo). Postoperative analgesia: epidural analgesia in groups A and B, systemic analgesia with opiates in groups C and D. Blood loss during surgery was monitored and salvaged with the Compact-A Dideco, and postoperative blood loss with the BT 797 Recovery Dideco for the first 24 hours. Perioperative blood loss, frequency and quantity of transfusions were significantly higher in group D (p<0.0001). Total blood loss was reduced by 31.3% by epidural anaesthesia, 20.4% by Aprotinin and 51.4% using a combination of the two techniques.

[alpha-Glucosidase inhibitors in the therapy of diabetes mellitus]. / Gli inhibitori delle alpha-glicosidasi nella terapia del diabete mellito.

The onset and progression of long-term complications in diabetes mellitus appear to be related to the degree of hyperglycemia and the overall metabolic control. Therefore, an important goal in the therapy of subjects with diabetes is to avoid wide fluctuations in blood glucose concentrations and increases in lipid levels. The first therapeutic maneuver to achieve glycemic control is to establish a correct diet containing complex carbohydrates and an adequate amount of dietary fibers. Dietary fibers are capable of reducing the intestinal uptake of carbohydrates. An additional strategy to reduce the uptake of carbohydrates across the intestine has recently been proposed by Puls et al. This strategy involves the use of inhibitors of alpha-glucosidase, an intestinal enzyme that participates in the breakdown of polysaccharides into disaccharides and monosaccharides. The inhibition of alpha-glucosidase by these agents is competitive and reversible and results in delayed and reduced uptake of carbohydrates across the intestine. This effect attenuates the post-prandial hyperglycemia and subsequent insulin secretory response particularly in subjects with hyperinsulinemia. The compound acarbose is a member of first generation alpha-glucosidase inhibitors. The administration of high doses of acarbose can be associated with side effects such as flatulence, meteorism, abdominal pain, and diarrhea due to the fermentation of non-absorbed carbohydrates in the intestinal lumen. Usually, these effects subside following a few days of therapy and/or reduction of the initial dose. Acarbose has been effectively used to treat type 2 diabetic patients either as a first choice drug or in association with sulfonylurea agents and in type 1 diabetics in association with insulin therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Attitudes of physicians regarding physician-assisted suicide.

A survey of New Jersey physicians reveals no clear consensus as to whether physician-assisted suicide should be legalized, and most physicians stated that they would not participate in such activities where it is legal to do so. Further studies need to be undertaken.

HCFA's Medicare mortality statistics for a New Jersey hospital.

We assessed the severity of illness in 40 Medicare patients with an acute myocardial infarction to determine whether HCFA's observed-to-predicted mortality ratio was related to quality of care or severity of illness. The authors present a study from a New Jersey hospital.

The Osborn wave of hypothermia in normothermic patients.

The Osborn wave (also referred to as "the J wave," "the J deflection," or "the camel's hump") is a distinctive deflection occurring at the QRS-ST junction of approximately 80% of hypothermic patients (core body temperature < or = 95 degrees F). Generally, the amplitude and duration of Osborn waves are inversely related to core temperature. We report on eight normothermic patients whose 12-lead electrocardiograms demonstrated QRS-ST junction notches similar to those seen in hypothermia. These data support the concept that the Osborn wave is not pathognomonic of hypothermia.

Combining three different sources as a valid tool to identify known diabetic patients: use in a prevalence study in an Italian local health unit.

This study was carried out to validate the prevalence of known diabetes estimated from three different simultaneous sources (medical records from out-patient departments, registers and pharmaceutical prescriptions) as against the diagnosis of family doctors who had received ad hoc training before the study. To this effect, a selected Local Health Unit (Unità Sanitaria Locale or USL) in Bari, southern Italy, was examined. 2917 diabetic patients were found, with a 2.82% prevalence. The prevalence of known diabetes estimated from separate sources was 1.41% from medical records, 1.52% from the registers and 1.59% from prescriptions. With reference to the family doctor's conclusions, sensitivity, positive predictive value and efficiency of medical records were 49.8%, 92.5% and 57.4% of USL registers 53.8%, 95.6% and 61.8% of prescriptions 56.3%, 71.2% and 47.9%. 46% of the diabetic subjects were only identified from one source. In conclusion, by combining several sources of information together, a higher number of diabetic patients are identified than would be done by using separate sources; also, active cooperation from the family practitioners seems to be needed to correct the large number of false positive patients (n = 798) mostly identified from prescriptions.

Advance directives for HIV-positive patients.

The authors surveyed HIV-positive patients to determine their knowledge of and interest in advance directives and their preferences for end-of-life care. The results of this study make clear the need to institute a program of education for those desiring to know more about advance directives.

On the frequency and reproducibility of orthostatic blood pressure changes in healthy community-dwelling elderly during 60-degree head-up tilt.

The postural effects of 20 minutes of 60-degree head-up tilt on systolic, diastolic, and mean arterial blood pressures (BPs), heart rate, and rhythm were studied in 70 healthy, community-dwelling volunteer subjects of both sexes, divided into three age groups. Group A consisted of 30 subjects, with a mean age of 76 years (range 65 to 95 years); group B had 19 subjects, with a mean age of 54 years (range 45 to 64 years); and group C had 21 subjects, with a mean age of 33 years (range 24 to 44 years). To qualify, subjects had to have a systolic BP of 150 mm Hg or less and a diastolic BP of < 90 mm Hg, be taking no prescribed medications, have had no previous syncopal episodes, and have absence of any significant medical illness. Nine of 30 (30%) subjects in group A, 1 of 19 (5%) subjects in group B, and 2 of 21 (9.5%) subjects in group C exhibited asymptomatic postural drops in systolic blood pressure > 20 mm Hg (p < 0.05). The mean time for the systolic blood pressure drops in group A was 9.2 minutes. Results were reproducible upon retesting after 1 week.

Advance directives for the elderly: a survey.

In 1991, the New Jersey Legislature passed the New Jersey Advance Directives for Health Care Act. We surveyed the elderly about their knowledge and interest in advance directives, their preferences regarding end-of-life care, and whether their physicians discuss these matters.