Effects on health-related quality of life of interventions affecting survival in critically ill patients: a systematic review.

Survival has been considered the cornerstone for clinical outcome evaluation in critically ill patients admitted to intensive care unit (ICU). There is evidence that ICU survivors commonly show impairments in long-term outcomes such as quality of life (QoL) considering them as the most relevant ones. In the last years, the concept of patient-important outcomes has been introduced and increasingly reported in peer-reviewed publications. In the present systematic review, we evaluated how many randomized controlled trials (RCTs) were conducted on critically ill patients and reporting a benefit on survival reported also data on QoL. All RCTs investigating nonsurgical interventions that significantly reduced mortality in critically ill patients were searched on MEDLINE/PubMed, Scopus and Embase from inception until August 2021. In a second stage, for all the included studies, the outcome QoL was investigated. The primary outcome was to evaluate how many RCTs analyzing interventions reducing mortality reported also data on QoL. The secondary endpoint was to investigate if QoL resulted improved, worsened or not modified. Data on QoL were reported as evaluated outcome in 7 of the 239 studies (2.9%). The tools to evaluate QoL and QoL time points were heterogeneous. Four interventions showed a significant impact on QoL: Two interventions improved survival and QoL (pravastatin in subarachnoid hemorrhage, dexmedetomidine in elderly patients after noncardiac surgery), while two interventions reduced mortality but negatively influenced QoL (caloric restriction in patients with refeeding syndrome and systematic ICU admission in elderly patients). In conclusion, only a minority of RCTs in which an intervention demonstrated to affect mortality in critically ill patients reported also data on QoL. Future research in critical care should include patient-important outcomes like QoL besides mortality. Data on this topic should be collected in conformity with PROs statement and core outcome sets to guarantee quality and comparability of results.

Bone Disruption and Environmental Pollutants.

BACKGROUND: Endocrine Disrupting Chemicals (EDCs) are ubiquitous and may significantly contribute to environmental pollution and contamination in humans and wildlife. Ecological pollutants could interfere with bone homeostasis through different mechanisms, including hormonal imbalance, direct osteoblast toxicity, and enhancement of osteoclasts activity, leading to either osteopenia or osteoporosis. Among these chemicals, bisphenols, dioxins, polycyclic aromatic hydrocarbons, polychlorobiphenyls, poly- and perfluoroalkyl, phthalates, parabens, organotins, and cadmium may play a role in the bone disruption. METHODS: Authors searched PubMed/MEDLINE, ISI-web of knowledge, and Google scholar databases for medical subject headings terms and free-text words related to the classes mentioned above of chemicals and bone metabolism and remodeling for better clarifying and understanding the main mechanisms of bone disruption. RESULTS: Several EDCs act as xeno-estrogens. Considering that estrogens play a significant role in regulating bone remodeling, most of these chemicals generate hormonal imbalance with possible detrimental consequences on bone tissue structure and its mechanical and non-mechanical properties. DISCUSSION: Much evidence about bone disruptors was obtained from in vitro studies or animal models with equivocal results. Besides, a few data have been acquired from humans, and most of these data focused on the impact of EDCs on bone mineral density without considering their influence on long-term fracture risk. Moreover, humans may be exposed to a mixture of EDCs, and the final effect on bone metabolism might be attributable to either synergistic or antagonist effects. Age of first exposure, cumulative exposure over time, and the usually observed non-monotonic dose-response curve for EDCs should be considered as other essential variables influencing bone metabolism's final effect. CONCLUSION: Given these variables, observational studies are needed to analyze this issue for ecological purposes better and preserve bone health.

Trigger and Target for Fibrinogen Supplementation Using Thromboelastometry (ROTEM) in Patients Undergoing Open Thoraco-Abdominal Aortic Aneurysm Repair.

OBJECTIVE: To determine the relationship between the value of fibrinogen assessed by the FIBTEM clot amplitude at 10 minutes (A10 FIBTEM) measured on admission to the intensive care unit (ICU) and the amount of drainage output at 24 hours, to investigate whether the A10 FIBTEM predicts severe bleeding (SB), and to define A10 FIBTEM thresholds to prevent (trigger) and treat (target) severe bleeding by fibrinogen supplementation. METHODS: In a single centre, retrospective observational study, 166 patients underwent elective open thoraco-abdominal aortic aneurysm (TAAA) repair between March 2016 and January 2019. Exclusion criteria were emergency, congenital, or acquired coagulopathy, or administration of P2Y12 inhibitor antiplatelet agents in the five days before surgery. All patients were managed intra-operatively and post-operatively according to a rotational thromboelastometry driven transfusion protocol. The principal endpoint was a composite outcome, which included bleeding, large volume transfusion, and re-operation. RESULTS: FIBTEM clot amplitude after 10 minutes measured on ICU admission and post-operative bleeding at 24 hours showed an inverse linear relationship (R2 = .03; p = .026). Performance of A10 FIBTEM in predicting SB evaluated by Receiving Operating Curve analysis showed an area under the curve of 0.63 (95% CI 0.56 - 0.70; p = .026) with a best cutoff of 9 mm. An A10 FIBTEM of 3 mm was the cutoff associated with a positive predictive value of 50%, while an A10 FIBTEM of 9 mm showed a negative predictive value of 92%. On multivariable analysis, an A10 FIBTEM ≤ 3 mm remained independently associated with SB. CONCLUSION: The present investigation shows for the first time in a population undergoing open TAAA repair that an A10 FIBTEM ≤ 3mm on ICU admission is associated with post-operative severe bleeding. Trigger and target values for fibrinogen supplementation, based on A10 FIBTEM, have been provided. The transferability and reliability of these cutoff values require further study.

Fast reshaping of intensive care unit facilities in a large metropolitan hospital in Milan, Italy: facing the COVID-19 pandemic emergency

At the end of 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak spread from China all around the world, causing thousands of deaths. In Italy, the hardest hit region was Lombardy, with the first reported case on 20 February 2020. San Raffaele Scientific Institute ­ a large tertiary hospital and research centre in Milan, Italy ­ was immediately involved in the management of the public health emergency. Since the beginning of the outbreak, the elective surgical activity of the hospital was rapidly reduced and large areas of the hospital were simultaneously reorganised to admit and assist patients with coronavirus disease 2019 (COVID-19). In addition, the hospital became the regional referral hub for cardiovascular emergencies in order to keep ensuring a high level of health care to non-COVID-19 patients in northern Italy. In a few days, a COVID-19 emergency department was created, improving the general ward capacity to a total number of 279 beds dedicated to patients with COVID-19. Moreover, the number of intensive care unit (ICU) beds was increased from 28 to 72 (54 of them dedicated to patients with COVID-19, and 18 to cardiology and cardiac surgery hub emergencies), both converting pre-existing areas and creating new high technology spaces. All the involved health care personnel were rapidly trained to use personal protection equipment and to manage this particular category of patients both in general wards and ICUs. Furthermore, besides clinical activities, continuously important research projects were carried out in order to find new strategies and more effective therapies to better face an unprecedented health emergency in Italy.

Sufentanil Sublingual Tablet System (SSTS) for the management of postoperative pain after major abdominal and gynecological surgery within an ERAS protocol: an observational study.

BACKGROUND: The Sufentanil Sublingual Tablet System (SSTS) is a new, pre-programmed, noninvasive, handheld system for patient-controlled analgesia (PCA) which may allow a faster postoperative recovery compared with standard PCA. The efficacy of SSTS in controlling pain after open abdominal surgery has already been documented. However, to our knowledge SSTS has never been investigated in patients undergoing major surgery within an Enhanced Recovery After Surgery (ERAS) protocol. METHODS: This observational, retrospective analysis included consecutive patients undergoing elective major abdominal and gynecological surgery. All patients received the SSTS device once they were fully awake and had a good control of pain at the end of the surgery. We analyzed changes in pain intensity according to the numerical rating scale (NRS) throughout the treatment as well as its duration, the number of administrations, and possible related adverse events. Patients were also interviewed to assess their quality of sleep and overall satisfaction with the SSTS device. RESULTS: The study included 308 patients. Compared to the first SSTS administration, pain intensity decreased from a median NRS of 6 to 0 at day 3, for an overall reduction of 79%. Results were already statistically significant at postoperative day 1 (p<0.01). Adverse reactions were observed in 62 patients, with nausea being the most frequent (12%), and in 93% of patients SSTS was discontinued because it was considered no longer necessary. Patient satisfaction was high, with 89% of them judging the device as "easy" or "very easy" to use. CONCLUSIONS: Although the retrospective and observational nature of the study as well as the absence of a comparative group limits the strength of evidence, our results consider SSTS an effective and safe tool for the management of postoperative pain after major abdominal and gynecological surgery within an ERAS protocol.

IRIS: methodological assessment of psychopathological disease in a cohort of hirsute women.

BACKGROUND: Hirsutism in females can be a source of considerable psychological distress and a threat to female identity. The aim of our study was to evaluate a possible relationship between facial, total body hair involvement and physical, mental and social well-being during 12 months of follow-up and treatment. Both objective and subjective methods of evaluating hirsutism were used: the Ferriman-Gallwey (FG) scoring method and the questionnaires General Health Questionnaire (GHQ)-12, Polycystic Ovary Syndrome Questionnaire (PCOSQ) and SF-12. METHODS: The total of 469 female patients (mean age 27.61±7.63 years) was enrolled in 27 Italian centers participating in this study. Higher total body score was correlated to significant emotional discomfort. The correlation between the FG total body score, the facial score and physical/mental health was found to be significant in all the patients assessed by SF-12 questionnaire. The ongoing reduction of GHQ-12 score was found for the facial FG score at the first follow-up (T0-T1 period) and at the second one (T0-T2). No relationship was found between T1 and T2. At both 6 (T1) and 12 months (T2) follow-up an increase of PCOSQ Score (psychological improvement) was accompanied by a concomitant reduction of the FG Score (reduction of hirsutism). Physical health assessed by SF-12 questionnaire does not change at both 6- and 12-month follow-up, but mental health decreased at both T1 and T2. RESULTS: The clinical improvement was achieved at 6 months regardless on treatment used and it was maintained for the next six-month follow-up. The clinical outcome could be assessed both by FG Score both through questionnaires administrated to each patient with hirsutism. CONCLUSIONS: For the evaluation of psychopathological discomfort the most appropriate questionnaire was GHQ-12, because of it major sensitivity to identify the psychological discomfort in the hirsutism.

Hypovitaminosis D in adolescents living in the land of sun is correlated with incorrect life style: a survey study in Campania region.

PURPOSE: The aim of this study is to investigate in a population of adolescents living in Regione Campania, undergoing sun exposure at least 9 months per year the prevalence of severe deficiency (<20 ng/ml) or insufficiency (21-29 ng/ml) of 25-Hydroxyvitamin D (25(OH)D) levels and its relationship with individual body weight, use of smoking, and exercise performance. METHODS: From October 2012 to October 2013, 373 healthy subjects (153 girls, 223 boys 11-20 years) without chronic diseases were consecutively enrolled in a campaign to prevent metabolic, cardiovascular, and oncological diseases. 25(OH)D assay, BMI, and lifestyle habitudes (smoking and exercise indoor or outdoor) were assessed. RESULTS: In this population, median 25(OH) level was 25.0 ng/ml (95 %CI 23.8-25.2) without any difference between girls (25.0 (95 %CI 23.1-25.7)) and boys (24.3 (95 %CI 23.8-25.2)). Severe deficiency was found in 6 girls (0.02 %), while insufficiency was found in 296 patients (110 girls, 79.3 %). Normal levels were found in 71 patients (37 girls, 19 %). Vitamin D levels were significantly correlated with BMI (r = -0.429, p < 0.0001), smoking (r = -0.241; p < 0.0001), and exercise performance (r = 0.791; p < 0.0001). At the multistep regression analysis, Vitamin D levels were best predicted by exercise performance (t = 19.6, p < 0.0001), less smoking addiction (t = -4.97, p < 0.001), and lower BMI (t = -4.69, p < 0.0001). CONCLUSIONS: The current study demonstrates that Vitamin D levels are commonly unsatisfactory in adolescents. Lower levels were found in overweight or obese adolescent, smokers and with low or absence of physical activity outdoors.

Pituitary tumors and pregnancy: the interplay between a pathologic condition and a physiologic status.

Pregnancy is becoming a relatively common event in patients with pituitary tumors (PT), due to the increasing availability of medical treatments, which control pituitary diseases associated with the development of PT. However, the presence of PT and its treatment may be a disturbing factor for pregnancy, and pregnancy significantly influences the course and the management of PT. This review summarizes the knowledge about the management of PT during pregnancy and the occurrence of pregnancy in patients with pre-existent PT, focusing on secreting PT characterized by hormonal excess and on clinically non-functioning PT often associated to hormone deficiency, which configure the hypopituitaric syndrome.

Comparison of the effects of primary somatostatin analogue therapy and pituitary adenomectomy on survival in patients with acromegaly: a retrospective cohort study.

OBJECTIVE: Acromegalic patients have an increased risk of mortality. The objective of this study was to compare the effect of different therapies for acromegaly on mortality. DESIGN AND METHODS: The mortality rate of 438 consecutive acromegalic patients was compared with that of the general population using the standardized mortality ratio (SMR); the effect of different therapies on survival was evaluated using Cox regression analysis. RESULTS: Twenty patients (4.5%) died between 1999 and 2009. Age- and sex-adjusted SMR was 0.70 (95% CI 0.43-1.08). The Cox regression analysis revealed that, in the whole population, both general risk factors (age and physical status) and specific factors for acromegaly (macroadenoma, hypopituitarism and uncontrolled disease) were associated with death. The most compromised patients at diagnosis had a higher mortality rate (P=0.001), which also occurred in patients with controlled acromegaly. Death occurred in 2.4% (adenomectomy), 2.6% (adenomectomy followed by somatostatin analogue (SSA) therapy) and 11.4% (SSA therapy as the primary therapy) of the patients. The risk of death was higher in patients receiving SSA therapy as the primary therapy (hazard ratio (HR) 5.52, 95% CI 1.06-28.77, P=0.043) than in all patients submitted to adenomectomy; however, a higher risk of death occurred only in diabetic patients treated with SSAs alone (HR 21.94, 95% CI 1.56-309.04, P=0.022). Radiotherapy was associated with an increased risk of mortality, which occurred in patients with the more locally advanced disease. CONCLUSIONS: Therapies for acromegaly and comorbidities have lowered the risk of mortality to the level of the general population; the effect of SSA therapy alone or that following pituitary adenomectomy was comparable to that of curative neurosurgery on survival in non-diabetic patients; on the contrary, SSA therapy as the primary therapy may be less effective than adenomectomy in reducing mortality rate in diabetic patients.

Limitations of Chromogranin A in clinical practice.

CONTEXT: Usefulness of circulating Chromogranin A (CgA) for the diagnosis of neuroendocrine tumors (NEN) is controversial. The aim of the present study was to assess the actual role of this marker as diagnostic tool. METHODS: Serum blood samples were obtained from 42 subjects affected with NEN, 120 subjects affected with non-endocrine neoplasias (non-NEN) and 100 non-neoplastic subjects affected with benign nodular goitre (NNG). Determination of CgA was performed by means of immunoradiometric assay. RESULTS: The CgA levels among NEN-patients were not significantly different from NNG and non-NEN subjects. The Receiver operating characteristic (ROC) curves analysis failed to identify a feasible cut-off value for the differential diagnosis between NEN and the other conditions. CONCLUSION: Serum CgA is not helpful for the first-line diagnosis of NEN.

PIT1 upregulation by HMGA proteins has a role in pituitary tumorigenesis.

We have previously demonstrated that HMGA1B and HMGA2 overexpression in mice induces the development of GH and prolactin (PRL) pituitary adenomas mainly by increasing E2F1 transcriptional activity. Interestingly, these adenomas showed very high expression levels of PIT1, a transcriptional factor that regulates the gene expression of Gh, Prl, Ghrhr and Pit1 itself, playing a key role in pituitary gland development and physiology. Therefore, the aim of our study was to identify the role of Pit1 overexpression in pituitary tumour development induced by HMGA1B and HMGA2. First, we demonstrated that HMGA1B and HMGA2 directly interact with both PIT1 and its gene promoter in vivo, and that these proteins positively regulate Pit1 promoter activity, also co-operating with PIT1 itself. Subsequently, we showed, by colony-forming assays on two different pituitary adenoma cell lines, GH3 and αT3, that Pit1 overexpression increases pituitary cell proliferation. Finally, the expression analysis of HMGA1, HMGA2 and PIT1 in human pituitary adenomas of different histological types revealed a direct correlation between PIT1 and HMGA expression levels. Taken together, our data indicate a role of Pit1 upregulation by HMGA proteins in pituitary tumours.

Therapy of aggressive pituitary tumors.

INTRODUCTION: Aggressive tumors of the pituitary gland are classically defined as pituitary tumors with a massive invasion of the surrounding anatomical structures and rapid growth. They are notoriously difficult to manage and are associated with poor prognosis because the therapeutic options are limited and the tumors are generally unresponsive to therapy. AREAS COVERED: This review focuses on treatment options for aggressive pituitary tumors, including surgery, radiotherapy and medical treatment, as well as focusing on the promising therapeutic options for aggressive pituitary tumors, evaluating the literature of the last 15 years. With the exception of prolactinomas, surgery is the first-line option, but most aggressive pituitary tumors often require repeated surgery. Pharmacotherapies are useful when surgery is unlikely to improve symptoms, or as an adjunct therapy to surgery. In prolactinomas, dopamine agonists are the first-line treatment and normalize prolactin levels in most patients, even those with macroprolactinomas. Somatostatin analogs are effective agents for primary therapy, pre-operatively or post-operatively to control tumor re-expansion of pituitary adenomas. However, dopamine agonists and somatostatin analogs are not as effective as they are for the treatment of non-aggressive adenomas. When surgery and pharmacotherapy fail, radiotherapy is a useful third-line strategy. Conventional chemotherapy is poorly effective but recent case reports with the temozolomide, an alkylating agent, have provided better results in the short term. EXPERT OPINION: Aggressive pituitary tumors are associated with poor prognosis as therapeutic options are limited. Moreover, they tend to recur quickly after initial treatment, are generally unresponsive to therapy, and are difficult to manage. To improve the overall response rate, the early application of current therapeutic approaches with the incorporation of new therapeutic developments is mandatory.

Resistance to somatostatin analogs in acromegaly.

Somatostatin analogs (SA) are widely used in acromegaly, either as first-line or adjuvant treatment after surgery. First-line treatment with these drugs is generally used in the patients with macroadenomas or in those with clinical conditions so severe as to prevent unsafe reactions during anesthesia. Generally, the response to SA takes into account both control of GH and IGF-I excess, with consequent improvement of clinical symptoms directly related to GH and IGF-I excess, and tumor shrinkage. This latter effect is more prominent in the patients treated first-line and bearing large macroadenomas, but it is also observed in patients with microadenomas, even with little clinical implication. Predictors of response are patients' gender, age, initial GH and IGF-I levels, and tumor mass, as well as adequate expression of somatostatin receptor types 2 and 5, those with the highest affinity for octreotide and lanreotide. Only sporadic cases of somatostatin receptor gene mutation or impaired signaling pathways have been described in GH-secreting tumors so far. The response to SA also depends on treatment duration and dosage of the drug used, so that a definition of resistance based on short-term treatments using low doses of long-acting SA is limited. Current data suggest that response to these drugs is better analyzed taking together biochemical and tumoral effects because only the absence of both responses might be considered as a poor response or resistance. This latter evidence seems to occur in 25% of treated patients after 12 months of currently available long-acting SA.

Pituitary carcinomas.

Pituitary carcinoma is a extremely rare and is characterized by a very poor prognosis. Even if at diagnosis the presence of metastases is required to define a pituitary carcinoma, the lesion was almost invariably diagnosed first as a benign pituitary tumor, that after a variable period of latency, ranging from few months to many years, changed its natural course to an aggressive pituitary tumor poorly responsive to therapy. Recent studies have partially clarified its molecular pathogenesis and found possible markers of aggressiveness in order to make an earlier diagnosis, when still treatment could improve their prognosis. Most pituitary carcinomas are functioning, and ACTH- and PRL-secreting carcinomas are the most frequent. Treatment includes surgery, radiotherapy, medical therapy and chemotherapy, but the poor results with current therapies should prompt all investigators to better understand its pathogenesis and searching new molecular targets for treatments.

The kidney in acromegaly: renal structure and function in patients with acromegaly during active disease and 1 year after disease remission.

BACKGROUND: The GH/insulin-like growth factor 1 axis is physiologically involved in the regulation of electrolytes and water homeostasis by kidneys, and influences glomerular filtration and tubular re-absorption processes. The aim of the study was to investigate renal structure and function in acromegalic patients during active disease and disease remission. PATIENTS: Thirty acromegalic patients (15 males and 15 females), aged 32-70 years, were enrolled for the study. Ten de novo patients had active disease, whereas 20 patients showed disease remission 1 year after medical treatment with somatostatin analogs (SA) (ten patients) or surgery (ten patients). Thirty healthy subjects matched for age, gender, and body surface area were enrolled as controls. RESULTS: In both active (A) and controlled (C) patients, creatinine clearance (P<0.001) and citrate (P<0.05) and oxalate levels (P<0.001) were higher, whereas filtered Na (P<0.001) and K (P<0.001) fractional excretions were lower than those in the controls. Urinary Ca (P<0.001) and Ph (P<0.05) levels were significantly increased compared with the controls, and in patients with disease control, urinary Ca (P<0.001) levels were significantly reduced compared with active patients. Microalbuminuria was significantly increased in active patients (P<0.05) compared with controlled patients and healthy control subjects. The longitudinal (P<0.05) and transverse (P<0.05) diameters of kidneys were significantly higher than those in the controls. In all patients, the prevalence of micronephrolithiasis was higher than that in the controls (P<0.001), and was significantly correlated to disease duration (r=0.871, P<0.001) and hydroxyproline values (r=0.639, P<0.001). CONCLUSIONS: The results of the current study demonstrated that acromegaly affects both renal structure and function. The observed changes are not completely reversible after disease remission.

Complete disappearance of a GH-secreting pituitary macroadenoma in a patient with acromegaly: effect of treatment with lanreotide Autogel and consequence of treatment withdrawal.

BACKGROUND: Somatostatin analogs (SA) are the cornerstone in the medical treatment of acromegaly, used as either primary or adjunctive therapy. In particular, SA are effective in inducing the biochemical remission of the disease and tumor shrinkage, although only few cases of complete disappearance of the pituitary tumor in patients treated with SA as long-acting formulations have been reported. SA withdrawal has been demonstrated to keep safe levels of GH and IGF1 at least in a small subset of patients well responsive to SA, although it is generally followed by disease recurrence after several months. CASE REPORT: A 61-year-old female patient bearing a very large GH-secreting pituitary macroadenoma was treated with 12-month lanreotide Autogel (ATG), at the initial dose of 120 mg/28 days. After 3 months, GH and IGF1 levels were fully normalized, to prolong the administration interval from 28 to 56 days. After 6 months of treatment, a significant tumor shrinkage (90% of baseline size) was observed, whereas GH and IGF1 excess was still well controlled. After 12-month therapy, a complete disappearance of the pituitary tumor was observed, and the hormonal evaluation confirmed the complete biochemical remission of acromegaly. Lanreotide ATG treatment was withdrawn. The clinical, biochemical, and radiological remission of acromegaly was maintained 24 months after lanreotide ATG treatment discontinuation, without evidence of disease recurrence. CONCLUSIONS: This report represents an exemplary case of the potentiality of treatment with lanreotide ATG in inducing a complete remission of acromegalic disease, persistent after a long period of time from treatment withdrawal.

Relationship between growth hormone/insulin-like growth factor-1 axis integrity and voluntary weight loss after gastric banding surgery for severe obesity.

BACKGROUND: The aim of this observational study was to determine, in a retrospective analysis, whether growth hormone (GH) and insulin-like growth factor-1 (IGF-1) at baseline or changes in the GH/IGF-1 axis after laparoscopic adjustable gastric banding (LAGB) is associated with weight loss and body composition changes in severely obese nondiabetic patients. METHODS: Weight loss (expressed as percent excess weight loss [EWL%]), anthropometry, body composition by bioelectrical impedance analysis (BIA), serum IGF-1, and GH peak after GH-releasing hormone (GHRH) plus arginine (ARG) test were measured and expressed as standard deviation scores (SDS) of reference values in 104 women and 36 men, age (mean +/- SD) 34 +/- 11 and 30.2 +/- 11 years, and BMI 44 +/- 5.7 and 39 +/- 3.2, respectively, before and 6 months after LAGB. RESULTS: After LAGB, 25% of women and 22.5% of men had GH deficiency, while 30.8% of women and 33.3% of men had IGF-1 deficiency or insufficiency. The median EWL was 36.8% in women and 40.0% in men. In both genders, percent decrease of waist circumference, EWL, and fat mass (FM) and percent increase of fat-free mass (FFM) was greater in patients with normal GH secretion and IGF-1 levels. The GH peak after GHRH + ARG, IGF-1 levels, and IGF-1 SDS were inversely correlated with EWL% (r = -0.50, r = -0.53, and r = -0.42, respectively; p < 0.0001) and percent FM (r = -0.41, r = -0.36, and r = -0.35, respectively; p < 0.0001). In stepwise linear regression analysis, the GH peak after GHRH + ARG was the major determinant of EWL% (p < 0.0001) and FM (p = 0.001). CONCLUSIONS: The efficacy of LAGB was greater in the patients with a normal GH response to GHRH + ARG and with normal IGF-1 levels. The percent of FM, FFM, and EWL were significantly correlated with the GH response to GHRH + ARG and with IGF-1 levels.