Fertility-Sparing Treatment for Early-Stage Cervical Cancer ≥ 2 cm: Can One Still Effectively Become a Mother? A Systematic Review of Fertility Outcomes.

BACKGROUND: Fertility-sparing treatments (FSTs) have played a crucial role in the management of early-stage cervical cancer (ECC); however, there is currently no standard of care for women with ECC ≥ 2 cm who wish to preserve their fertility. The current orientation of the scientific community comprises upfront surgical techniques and neoadjuvant chemotherapy (NACT) followed by minor surgery such us conization. However these approaches are not standardized. This systematic review aimed to collect the evidence in the literature regarding the obstetric outcomes of the different techniques for applying FSTs in ECC ≥ 2 cm. METHODS: A systematic review was performed in September 2022 using the Pubmed and Scopus databases, from the date of the first publication. We included all studies containing data regarding pregnancy, birth, and preterm rates. RESULTS: Fifteen studies fulfilled the inclusion criteria, and 352 patients were analyzed regarding fertility outcomes. Surgery-based FST showed the pregnancy rate (22%), birth rate (11%), and preterm rate (10%). Papers regarding FST using the NACT approach showed a pregnancy rate of 44%, with a birth rate of 45% in patients who managed to get pregnant. The preterm rate amounted to 44%, and pregnancy rates and birth rates were significantly different between the two groups (p < 0.001). CONCLUSION: Fertility preservation in patients with ECC > 2 cm is challenging. The endpoint for evaluating the best treatment should include oncological and fertility outcomes together. From this prospective, NACT followed by less radical surgery could be a reasonable compromise.

Prediction and evaluation of resting energy expenditure in a large group of obese outpatients.

BACKGROUND/OBJECTIVES: The aim of this study was to compare resting energy expenditure (REE) measured (MREE) by indirect calorimetry (IC) and REE predicted (PREE) from established predictive equations in a large sample of obese Caucasian adults. SUBJECTS/METHODS: We evaluated 1851 obese patients (body mass index (BMI)>30 kg m-2) aged between 18a and 65 years. Data were obtained by comparing MREE with PREE, derived from different equations, within and between normal weight and obese groups. The mean differences between PREE and MREE as well as the accuracy prediction within ±10% level were investigated in the whole sample and in three subgroups, classified by BMI (Group 1=30-39.9 kg m-2; Group 2=40-49.9 kg m-2; Group 3>50 kg m-2). RESULTS: We observed that FAO, Henry and Muller3 (body composition (BC)) equations provided good mean PREE-MREE (bias -0.7, -0.3 and 0.9%; root mean standard error (RMSE) 273, 263 and 269 kcal per day, respectively); HB and Henry equations were more accurate individually (57 and 56.9%). Only the Muller1 (BC) equation gave the lowest PREE-MREE difference (bias -1.7%; RMSE 228 kcal per day) in females, while Johnstone and De Lorenzo equations were the most accurate (55.1 and 54.8%). When the sample was split into three subgroups according to BMI, no differences were found in males; however, the majority of the equations included in this study failed to estimate REE in severely obese females (BMI>40 kg m-2). Overall, prediction accuracy was low (~55%) for all predictive equations, regardless of BMI. CONCLUSIONS: Different established equations can be used for estimating REE at the population level in both sexes. However, the accuracy was very low for all predictive equations used, particularly among females and when BMI was high, limiting their use in clinical practice. Our findings suggest that the validation of new predictive equations would improve the accuracy of REE prediction, especially for severely obese subjects (BMI>40 kg m-2).

Hematological complications in anorexia nervosa.

BACKGROUND/OBJECTIVES: Anemia, leukopenia and, although less frequently, thrombocytopenia are possible hematological complications of anorexia nervosa considered strictly secondary to chronic malnutrition. This is a retrospective study on the prevalence of these disorders in a large cohort of 318 female patients with AN (20.4±5.6 years, body mass index (BMI) 15.9±1.6 kg/m2), recruited in the Outpatient Unit for Malnutrition secondary to Eating Disorders at the Department of Clinical Medicine and Surgery, Federico II University Hospital, since February 1991 to December 2012. SUBJECTS/METHODS: Patients were studied on an outpatient basis after obtaining medical history, clinical examination, routine hematobiochemical and endocrine tests, electrocardiography, psychiatric interview and bioelectrical impedance analysis and, in particular, phase angle determination. All patients with other comorbidities, in particular with mean corpuscular volume <80 fl, were excluded for suspected genetic alteration in the synthesis of hemoglobin. RESULTS: Hematologic data showed that 16.7% of patients had anemia, 7.9% neutropenia and 8.9% thrombocytopenia. These abnormalities were strictly related to the duration of illness (P=0.028), and to protein energy malnutrition, in particular, BMI and phase angle (P<0.001). CONCLUSIONS: Our study offers description of the incidence of hematologic defects in a selected and large sample of AN female patients, suggesting that its incidence is related to the degree and duration of protein energy malnutrition.

Iron absorption following a single oral dose of ferrous sulfate or ferric gluconate in patients with gastrectomy.

BACKGROUND: Iron deficiency anemia frequently occurs in gastrectomized patients. METHODS: Serum iron levels following the ingestion of a single oral dose of 105 mg elemental iron, taken as ferrous sulfate (FeS) or ferric gluconate (FeG), have been evaluated in 20 gastrectomized patients (and 20 controls). All subjects participated on 2 different test days, 1 month apart: they took a single dose of 105 mg elemental iron as FeS or FeG after a night of fasting. Serum iron concentrations at baseline, 30, 60, 120 and 180 min after the oral dose administration were measured. RESULTS: In patients and controls receiving FeG, serum iron levels did not significantly change. After oral ingestion of FeS, patients' serum iron levels gradually increased. The increase in serum iron levels was 148 and 168% at 120 and 180 min in patients (p < 0.0001 for both evaluations), whilst in controls, it was 216% at 120 min and 234% at 180 min, i.e. significantly higher than in gastrectomized patients (p < 0.001 for both evaluations). CONCLUSIONS: In gastrectomized patients, a single oral dose of FeS shows a significant increase in iron serum concentration, albeit lower than in controls. Further studies on a larger sample of patients will be necessary to confirm these results.

The absence of polymorphisms in ADRB3, UCP1, PPARγ, and ADIPOQ genes protects morbid obese patients toward insulin resistance.

BACKGROUND AND AIMS: The insulin resistance (IR) is a major metabolic impairment in severe obesity, a multifactorial disease in which the importance of the effect of single nucleotide polymorphisms (SNP) associations in different rather than individual genes was established. The aim of this study was to test the predictive value of presence/absence of polymorphisms/ variants in ß3-adrenergic receptor (ADRB3), uncoupling protein 1 (UCP1), peroxisome proliferator-activated receptor γ (PPARγ), and adiponectin (ADIPOQ) genes in diagnosing the IR in obesity. SUBJECTS AND METHODS: We studied 112 (40 males, 72 females) severely obese (body mass index: 48.5±7.5 kg/m2) subjects recruited from the outpatient obesity clinic of Federico II University Hospital in Naples. Genomic DNA was extracted from peripheral leukocytes with a commercial kit. The gene polymorphisms Trp64Arg in ADRB3, -3826 A>G in UCP1, Pro12Ala in PPARγ, and c.268G>A, c.331T>C, and c.334C>T in ADIPOQ were characterized by TaqMan assay or by direct sequencing (ADIPOQ). RESULTS AND CONCLUSION: Our results demonstrate that -3826A>G UCP1 polymorphism is associated with IR in morbid obesity. Further, the lack of any polymorphisms, Trp64Arg in ADRB3 and/or -3826 A>G in UCP1 and/or Pro12Ala in PPARγ and/or c.268G>A, c.331T>C and c.334C>T in ADIPOQ, appears a useful prognostic factor (NPV=100%) toward the IR onset in these obese patients representing a further parameter for an earlier and appropriate therapy.

Four novel UCP3 gene variants associated with childhood obesity: effect on fatty acid oxidation and on prevention of triglyceride storage.

OBJECTIVE: The objective of the study was to look for uncoupling protein 3 (UCP3) gene variants in early-onset severe childhood obesity and to determine their effect on long-chain fatty acid oxidation and triglyceride storage. METHODS AND RESULTS: We identified four novel mutations in the UCP3 gene (V56M, A111V, V192I and Q252X) in 200 children with severe, early-onset obesity (body mass index-standard deviation score >2.5; onset: <4 years) living in Southern Italy. We evaluated the role of wild-type (wt) and mutant UCP3 proteins in palmitate oxidation and in triglyceride storage in human embryonic kidney cells (HEK293). Palmitate oxidation was ∼60% lower (P<0.05; P<0.01) and triglyceride storage was higher in HEK293 cells expressing the four UCP3 mutants than in cells expressing wt UCP3. Moreover, mutants V56M and Q252X exerted a dominant-negative effect on wt protein activity (P<0.01 and P<0.05, respectively). Telmisartan, an angiotensin II receptor antagonist used in the management of hypertension, significantly (P<0.05) increased palmitate oxidation in HEK293 cells expressing wt and mutant proteins (P<0.05; P<0.01), including the dominant-negative mutants. CONCLUSIONS: These data indicate that protein UCP3 affects long-chain fatty acid metabolism and can prevent cytosolic triglyceride storage. Our results also suggest that telmisartan, which increases fatty acid oxidation in rat skeletal muscle, also improves UCP3 wt and mutant protein activity, including the dominant-negative UCP3 mutants.

[Obesity and Eating Disorders. Indications for the different levels of care. An Italian Expert Consensus Document]. / Documento di Consensus. Obesità e Disturbi dell'Alimentazione Indicazioni per i diversi livelli di trattamento.

This paper is an Italian Expert Consensus Document on multidimensional treatment of obesity and eating disorders. The Document is based on a wide survey of expert opinion. It presents, in particular, considerations regarding how clinicians go about choosing the most appropriate site of treatment for a given patient suffering from obesity and/or eating disorders: outpatient, partial hospitalization, residential rehabilitation centre, inpatient hospitalization. In a majority of instances obesity and eating disorders are long-term diseases and require a multiprofessional team-approach. In determining an initial level of care or a change to a different level of care, it is essential to consider together the overall physical condition, medical complications, disabilities, psychiatric comorbidity, psychology, behaviour, family, social resources, environment, and available services. We first created a review manuscript, a skeleton algorithm and two rating scales, based on the published guidelines and the existing research literature. As the second point we highlighted a number of clinical questions that had to be addressed in the specific context of our National Health Service and available specialized care units. Then we submitted eleven progressive revisions of the Document to the experts up to the final synthesis that was approved by the group. Of course, from point to point, some of the individual experts would differ with the consensus view. The document can be viewed as an expert consultation and the clinical judgement must always be tailored to the particular needs of each clinical situation. We will continue to revise the Document periodically based on new research information and on reassessment of expert opinion to keep it up-to-date. The Document was not financially sponsored.