Efficacy of liraglutide 3.0 mg treatment on weight loss in patients with weight regain after bariatric surgery.

PURPOSE: Bariatric surgery, as Roux-en-Y gastric bypass (RYGB), laparoscopic gastric banding (LGB), and laparoscopic sleeve gastrectomy (LSG), is considered the gold standard treatment to achieve long-term weight loss in severe obesity. In patients who fail to maintain the achieved weight, pharmacological treatment may be required. Here, we reported our real-life experience on the efficacy of liraglutide therapy in 62 patients who regained weight after bariatric surgery. METHODS: We retrospectively evaluated 62 (60 F-2 M; mean age: 43.6 ± 9.9 years) patients received liraglutide for weight loss after bariatric surgery (17 RYGB, 22 LGB, and 23 LSG). Body mass index (BMI) before and after surgery was, respectively, of 45.4 ± 5.5 kg/m2 and 29.5 ± 4.9 kg/m2. Patients were followed up from 2016 until 2021. Liraglutide was administered after weight regain once-daily subcutaneously at starting dose of 0.6 mg and with weekly increases up to 3.0 mg. Treatments were administered when a weight regain of 10-15% occurred after reaching a minimum weight loss from bariatric surgery or if weight loss after bariatric surgery was unsatisfactory. RESULTS: After a mean of 70.7 ± 43.7 months from any bariatric surgery, all patients started liraglutide therapy. At this time, mean BMI was 34.2 ± 4.8 kg/m2 (mean increased BMI: 4.7 ± 2.8 kg/m2). After a mean of 10.5 ± 4.4 months from the beginning of liraglutide, 9 patients achieved normal weight (BMI 24.1 ± 0.9 kg/m2), and 28 were overweight (BMI 26.9 ± 1.6 kg/m2). Twenty patients achieved grade I (BMI 32.1 ± 1.5 kg/m2), 5 grade II (BMI 37.3 ± 2.0 kg/m2) obesity, and none had grade III obesity (mean BMI change: - 5.1 ± 2.5 kg/m2). The treatment was well tolerated, and no serious adverse events were recorded. CONCLUSION: These data confirm the efficacy and safety of liraglutide in patients who experienced weight regain after bariatric surgery. Considering the long-term follow-up, patients should be followed up regularly and the pharmacological treatment should be adapted to the weight fluctuations observed during the clinical history. LEVEL OF EVIDENCE: V. Opinions of authorities, based on descriptive studies, narrative reviews, clinical experience, or reports of expert committees.

Hysteroscopic permanent tubal sterilization using a nitinol-dacron intratubal device without anaesthesia in the outpatient setting: procedure feasibility and effectiveness.

BACKGROUND: Hysteroscopic permanent tubal sterilization has recently been introduced, resulting in a non-invasive, safe and effective technique. The aim of this study was to assess the feasibility of outpatient hysteroscopic tubal sterilization using a nitinol-dacron intratubal device without anaesthesia and to assess patient procedure compliance. MATERIALS AND METHODS: We untertook a prospective study of 36 consecutive cases of outpatient hysteroscopic tubal sterilization using a nitinol-dacron intratubal device without anaesthesia. Tubal sterilization was performed by placing the device with the aid of a 5.2-mm continuous-flow operative hysteroscope. At the end of the procedure women were asked to rate the pain experienced on a visual analogue scale (VAS) (0, no discomfort to 100, severe discomfort). Successful device placement was assessed after 3 months by hysterosalpingography and diagnostic hysteroscopy. RESULTS: Successful bilateral placement was obtained in 32 patients (88.9%); in one (2.8%) the placement was monolateral; and in three (8.3%) the procedure failed. Mean operating time was 8.6 +/- 5.3 min. A mean VAS of 36.1 +/- 23.9 was recorded. CONCLUSIONS: The nitinol-dacron intratubal device is safe, appears to be effective long-term, is non-invasive and can be used in the outpatient setting without anaesthesia. Low-level discomfort was experienced by the patients. Limitations of its use include that it is not effective immediately, it is irreversible, it requires special equipment and training, and it is difficult to use in cases of uterine anomalies. We conclude that this method may be offered to all woman asking for permanent tubal sterilization, particularly those who refuse or have contraindications for anaesthesia.

Adenosarcoma of the ovary. A case report.

Adenosarcoma of the ovary is a rare condition. We report a case of a 32-year-old patient that has been treated in our Department. The diagnosis of ovarian adenosarcoma was carried out after laparoscopy with removal of an ovarian endometriotic cyst. Laparoscopic homolateral ovariectomy was then performed and conservative treatment was decided on considering the young age, low stage and low grade of the disease. Second-look laparoscopy, clinical evaluation and ultrasound were performed for four years of follow-up. No recurrence has been detected. Conservative treatment should be proposed in fertile age with low-grade ovarian adenosarcoma, but a strict follow-up is always necessary.

Laparoscopic management of early stage endometrial cancer.

PURPOSE OF INVESTIGATION: The purpose of this study was to evaluate the feasibility of laparoscopic hysterectomy versus the transabdominal approach with systemic pelvic lymphadenectomy in early stage endometrial cancer. METHODS: From January 1996 to April 2002, 59 women were treated for endometrial cancer at the Department of Gynecology in Padova, Italy (29 by the laparoscopic technique and 30 by laparotomy). Every patient underwent hysterosalpingo-oophorectomy with systemic pelvic lymphadenectomy. RESULTS: Comparing the two techniques, operating time was longer and hospital stay was significantly shorter for laparoscopy; no differences were observed about the number of removed lymph nodes (range 5-33) or intra-postoperatory complications. CONCLUSION: The laparoscopic approach to endometrial cancer is certainly to be considered appropriate and efficacious, even if it requires skilled surgeons and adequate oncologic training. It is important to perform pelvic lymphadenectomy in all cases of early stage cancer.

Protein S deficiency. Description of a case associated with chronic inflammatory bowel disease.

Thrombotic disease is one of the most relevant clinical problems for morbility and mortality. We can differentiate congenital and acquired forms. In this short communication we describe 1 case observed by us that seems interesting for the association of a congenital and acquired form [Protein S deficiency and inflammatory bowel disease (IBD)] and for the dramatic events suffered before receiving a complete diagnosis and therapy, indicating the importance of recollection of information from the patients, starting from anamnestic data.

Cardioprotective effects of zofenopril, a new angiotensin-converting enzyme inhibitor, on doxorubicin-induced cardiotoxicity in the rat.

We have studied the effect of zofenopril, a new angiotensin-converting enzyme inhibitor in preventing cardiac injury induced by chronic doxorubicin treatment in rats. Cardiac function was assessed by measuring changes in electrocardiogram (ECG) tracings, haemodynamics and cardiac responses in vivo to isoprenaline, 4 weeks after suspension of doxorubicin treatment, in vehicle-treated rats and in animals receiving zofenopril (15 mg/kg/os/day) alone, doxorubicin (1.5 mg/kg i.v. once a week for 5 weeks) or zofenopril+doxorubicin treatment. Doxorubicin induced a significant lengthening of the QalphaT interval, which was completely prevented by zofenopril treatment. The cardiac positive inotropic effect induced by i.v. isoprenaline was selectively depressed by doxorubicin (no changes in chronotropic responses) and this adverse effect of doxorubicin was also prevented in zofenopril+doxorubicin pretreated rats. Doxorubicin induced a significant increase in relative heart weight, which was likewise prevented in zofenopril+doxorubicin treated rats. In separate experiments, zofenopril did not interfere with the antitumor activity of doxorubicin (inhibition of tumor growth in nude mice xenografted with A2780 human tumor line). In conclusion, the oral administration of zofenopril is able to significantly ameliorate, up to 4 weeks after the end of doxorubicin administration, doxorubicin-induced cardiotoxicity without affecting the antitumor activity of this anthracycline.

Pharmacology of MEN 11467: a potent new selective and orally- effective peptidomimetic tachykinin NK(1) receptor antagonist.

We have investigated the pharmacological properties of MEN 11467, a novel partially retro-inverse peptidomimetic antagonist of tachykinin NK(1) receptors. MEN 11467 potently inhibits the binding of [(3)H] substance P (SP) to tachykinin NK(1) receptors in the IM9 limphoblastoid cell line (pK(i) = 9.4 +/- 0.1). MEN 11467 is highly specific for the human tachykinin NK(1) receptors, since it has negligible effects (pK(i) <6) on the binding of specific ligands to tachykinin NK(2) or NK(3) receptors and to a panel of 30 receptors ion channels unrelated to tachykinin receptors. The antagonism exerted by MEN 11467 at tachykinin NK(1) receptors is insurmountable in saturation binding experiments, both K(D) and B(max) of SP were significantly reduced by MEN 11467 (0.3-10 nM). In the guinea-pig isolated ileum, MEN 11467 (0.03-1 nM) produced a nonparallel rightward shift of the concentration-response curve to SP methylester with a concomitant reduction of the Emax to the agonist (pK(B) = 10.7 +/- 0.1). Moreover the antagonist activity of MEN 11467 was hardly reversible despite prolonged washout. In vivo, MEN 11467 produced a long lasting (> 2-3h) dose-dependent antagonism of bronchoconstriction induced by the selective tachykinin NK(1) receptor agonist, [Sar(9), Met(O(2))(11)]SP in anaesthetized guinea-pigs (ID(50)s' = 29+/-5, 31+/-12 and 670+/-270 microg/kg, after intravenous, intranasal and intraduodenal administration, respectively), without affecting bronchoconstriction induced by methacholine. After oral administration MEN 11467 produced a dose-dependent inhibition of plasma protein extravasation induced in guinea-pig bronchi by [Sar(9), Met(O(2))(11)] (ID(50) = 6.7 +/- 2 mg/kg) or by antigen challenge in sensitized animals (ID(50) = 1.3 mg/kg). After i.v. administration MEN 11467 weakly inhibited the GR 73632-induced foot tapping behaviour in gerbil (ED(50) = 2.96 +/- 2 mg/kg), indicating a poor ability to block central tachykinin NK(1) receptors. These results demonstrate that MEN 11467 is a potent, highly selective and orally effective insurmountable pseudopeptide antagonist of peripheral tachykinin NK(1) receptors with a long duration of action.

Comparison of doxorubicin- and MEN 10755-induced long-term progressive cardiotoxicity in the rat.

The delayed functional cardiotoxic effects of repeated treatment with the new disaccharide anthracycline MEN 10755 and doxorubicin (1.5 mg/kg, i.v., once a week for 5 consecutive weeks) were investigated in the rat. Changes were assessed (2 days and 4 and 13 weeks after the last treatment) in ECG morphology, hemodynamics, in vivo left ventricular contractile responses to beta-adrenergic stimulation, and histopathology of both atria and ventricles. Doxorubicin induced significant and progressive prolongation of the QalphaT interval starting 2 days after suspension of treatment. At 4 and 13 weeks after the last treatment, the ECG showed a further progressive and significant impairment. MEN 10755 induced alterations similar in nature but of lesser severity compared with doxorubicin. In addition, MEN 10755-induced prolongation of the QalphaT interval was not progressive, being similar at 4 and 13 weeks after the last treatment. Although the hemodynamics were only slightly affected by both anthracyclines, a nearly complete ablation of isoprenaline-induced enhancement of ventricular function was observed 4 and 13 weeks after the last treatment with doxorubicin, whereas only mild, if any, reduction was detected in rats receiving MEN 10755. Histopathologic investigations indicated that both anthracyclines produced qualitatively similar alterations in ventricular myocytes. However, only with doxorubicin did these changes show a progression with a further significant worsening at 13 weeks as compared with 4 weeks after the last treatment. In addition, atrial lesions were evident in doxorubicin-treated rats, but not in rats receiving MEN 10755. In conclusion, an equimyelotoxic regimen of MEN 10755 produced, as compared with doxorubicin, lesser ECG alterations, smaller impairment of the ventricular response to adrenergic stimulation, and less severe myocyte lesions. Unlike doxorubicin, the histologic and functional cardiotoxic effects induced by MEN 10755 were not progressive. Further investigations are warranted to define the pharmacodynamic and/or pharmacokinetic mechanism(s) underlying the different cardiotoxic profile exhibited by the two anthracyclines.

Long-term evaluation of T-cell subsets and T-cell function after HAART in advanced stage HIV-1 disease.

OBJECTIVES: Evaluation of immunological reconstitution after 2 years of highly active antiretroviral therapy (HAART) in AIDS patients. DESIGN: Previous data showed the effectiveness of HAART but conflicting evidence of immune reconstitution has been found in severely immunocompromised patients. Therefore, T-cell subsets and functions were analysed during 24 months of HAART in 21 AIDS patients (mean baseline CD4 cell count, 20 x 10(6)/l). METHODS: Subjects were tested at baseline and after 4, 12 and 24 months of therapy for clinical symptoms and the following investigations were carried out: plasma HIV RNA, T-cell subsets and lymphoproliferative responses to mitogens (phytohaemagglutinin, anti-CD3), and recall antigens (Candida mannoprotein, tetanus toxoid and recombinant glycoprotein 160). RESULTS: Increase in body weight, improvement of Karnofsky's score and reduction of opportunistic infections were observed. All patients showed an initial increase in the CD4 memory subset, whereas naive CD4 cells consistently increased only after 1 year. The magnitude of immune recovery was stronger in patients showing a significant reduction in viral load. However seven out of 21 patients who did not reach a sustained suppression of viral load showed also an increase in T-cell subsets. The majority of patients recovered lymphoproliferative responses to mitogens, whereas only four subjects showed a functional response to Candida mannoprotein. No patients showed a response to HIV recombinant glycoprotein 160 or tetanus toxoid. CONCLUSIONS: The immune recovery observed is slower and not complete in severely immunocompromised patients. Our data suggest that HAART may be continued also in the absence of a significant HIV RNA decrease if alternative drugs are not available.

Hepatitis C virus infection in Italian patients with hypogammaglobulinemia.

We investigated the presence of hepatitis C virus (HCV) infection in 58 patients with humoral immunodeficiencies. Forty-three of these patients had common variable immunodeficiency (CVI), 2 had sporadic hyperimmunoglobulin M (HIM) syndrome, 2 had immunoglobulin G subclass deficiency, 4 had ataxia-telangiectasia (AT), and 7 had X-linked agammaglobulinemia (XLA). Patients with late-onset hypogammaglobulinemia (those with CVI, HIM, or immunoglobulin G subclass deficiency) had a 38.2% prevalence of HCV infection. In patients with XLA or AT, HCV infection was not detectable. Most of the HCV-infected patients had persistent viremia, with histologic findings of chronic hepatitis. Although patients positive for HCV ribonucleic acid (RNA) had received several lots of immunoglobulin, we were unable to detect any correlation between the time that alanine aminotransferase levels increased and the time that intravenous immunoglobulin therapy was given, except in one patient with CVI. Moreover, we found no differences in the number of blood transfusions, surgical procedures, or administrations of intravenous or intramuscular immunoglobulin between HCV RNA-positive and HCV RNA-negative groups. We concluded that: (1) the incidence of HCV infection in patients with hypogammaglobulinemia is much higher than that reported in the Italian general population; (2) although patients with hypogammaglobulinemia have persistent viremia, they do not show an aggressive course of HCV disease, nor does hepatocarcinoma develop; and (3) intravenous immunoglobulins are only one of several possible causes of HCV transmission in patients with humoral immunodeficiencies.

Fibroblast-derived factors preserve viability in vitro of mononuclear cells isolated from subjects with HIV-1 infection.

OBJECTIVE: Peripheral blood mononuclear cells (PBMC) from HIV-infected subjects have an increased mortality rate (MR) when incubated in vitro for 3 days in a culture medium. We have previously shown that fibroblast-conditioned medium (FCM) can preserve viability, without significant activation, of human lymphocytes in vitro. We therefore tested the ability of two FCM and other factors to reduce spontaneous MR in HIV-positive PBMC. METHODS: PBMC were cultured for 3 days in control medium and medium supplemented with FCM or recombinant cytokines [interleukin (IL)-2, IL-6, IL-7, granulocyte macrophage colony-stimulating factor]. Cells viable at day 3 were counted in a cytofluorimeter after staining with ethidium bromide. DNA was extracted from the cultures and evaluated for the presence of low molecular weight fragmentation. RESULTS: The MR of PBMC from 51 HIV-positive subjects and from 21 healthy controls were 30.1 and 9.5%, respectively (P < 0.0001). The MR was higher in 40 patients with a CD4+ lymphocyte count < 400 x 10(6)/l than in subjects with a count > 400 x 10(6)/l (32.84 versus 20.96%; P = 0.047). IL-2 and FCM significantly reduced MR in HIV-positive subjects (MR: 17.8 and 20.4%; P: < 0.001 and 0.005, respectively). This effect was more evident in subjects with a CD4+ lymphocyte count < 400 x 10(6)/l and in subjects with negative p24 antigenaemia. Cellular proliferation accounts for increased survival in IL-2-supplemented cultures but not in those with FCM. DNA was extracted from fresh PBMC and cells cultured for 3 days for 22 HIV-positive cases. DNA degradation was documented and bands related to an apoptotic mechanism of death observed, especially in subjects with more advanced disease. CONCLUSIONS: Our data suggest that FCM inhibits accelerated cell death in vitro of PBMC isolated from HIV-positive patients.

Evaluation of children with medullary thyroid carcinoma.

Early diagnosis and surgical treatment of medullary thyroid carcinoma (MTC) in children is essential to decrease the likelihood of metastatic spread. From 1981 to 1991, eight children under 18 years of age (five girls and three boys) with MTC were seen and seven underwent total thyroidectomy. Follow-up ranged from 14 months to 10 years after surgery. Four of the seven presented with a neck mass and elevated basal levels of calcitonin (CT). After surgery, three had recurrent disease. In the other three, the diagnosis was made after several years of screening (normal basal values of CT but increased CT levels after calcium/pentagastrin infusion). All had normal stimulated CT values postoperatively. This follow-up showed that the prognosis for MTC in children depends predominantly upon its extent at the time of the diagnosis and treatment.

Use of somatostatin analog SMS 201-995 in medullary thyroid carcinoma.

We have studied seven subjects with medullary thyroid carcinoma. Each had elevated basal serum calcitonin (CT) levels following total thyroidectomy. After subcutaneous administration of 100 micrograms of SMS 201-995, blood samples were collected at 60-minute intervals for six hours. Two patients showed a marked decrease of CT levels (patient A: baseline 565 pg/mL, nadir 150 pg/mL; patient B: baseline 1,632 pg/mL, nadir 416 pg/mL). The other five patients showed no significant change in comparison with saline infusion. Two patients were treated with SMS 201-995 (300 micrograms/day) for 90 days. One of these patients responded to the acute SMS 201-995 test and had CT levels persistently 50% lower than pretreatment values during this 90-day period. The other patient, whose CT levels did not decrease during the acute test, had persistently high values during this 90-day period but had relief of watery diarrhea even after the therapeutic trial was discontinued.

The role of radiopharmaceuticals MIBG and (V) DMSA in the diagnosis of medullary thyroid carcinoma.

The diagnostic value of 123/131I meta-iodo-benzylguanidine (MIBG) and 99mTc (V) dimercaptosuccinic acid (DMSA) was investigated in 12 patients with proven medullary thyroid carcinoma (MTC). Scintigraphic imaging with DMSA was negative in nine of 12 patients. Scintigraphy with MIBG was positive in only one case. In proven primary or recurrent disease, DMSA sensitivity was 50% and MIBG sensitivity was 25%. Such sensitivities become much lower in subjects with high calcitonin (CT) levels who have had negative surgical explorations: DMSA 17% and MIBG 0%. DMSA detected tumor in 25% of the patients and MIBG in only 8%. The positivity of these scintigraphies appears to be unrelated to carcinoembryonic antigen and CT plasma levels. Such data suggest that scintigraphies with MIBG and DMSA are only modestly useful in the diagnosis of MTC.

Clinical course of Crohn's disease in Italy.

The clinical course of Crohn's disease in 131 patients was studied for a mean period of 4.2 +/- 3.2 years. The clinical activity of the disease, expressed as percentage of patients per year in an active phase, is high in the first year (70.2 percent) and progressively decreases during subsequent years (25 percent after seven years). The percentage of patients who needed steroid treatment is high during the first year (68 percent) and falls to 19 percent after seven years. An operative risk rate of 54 percent was registered, with a probability of reoperation equal to 34 percent. Clinical relapse after the first surgery occurred in 70 percent of cases. The registered mortality was 6.9 percent, with a ratio of 6 to 1 between observed and expected mortality. In conclusion, the disease, while showing a tendency to reduce its activity over the years, is burdened by a risk of surgery and mortality which progressively increases with time.