Very-low-calorie ketogenic diet (VLCKD) in the management of metabolic diseases: systematic review and consensus statement from the Italian Society of Endocrinology (SIE).

BACKGROUND: Weight loss is a milestone in the prevention of chronic diseases associated with high morbility and mortality in industrialized countries. Very-low calorie ketogenic diets (VLCKDs) are increasingly used in clinical practice for weight loss and management of obesity-related comorbidities. Despite evidence on the clinical benefits of VLCKDs is rapidly emerging, some concern still exists about their potential risks and their use in the long-term, due to paucity of clinical studies. Notably, there is an important lack of guidelines on this topic, and the use and implementation of VLCKDs occurs vastly in the absence of clear evidence-based indications. PURPOSE: We describe here the biochemistry, benefits and risks of VLCKDs, and provide recommendations on the correct use of this therapeutic approach for weight loss and management of metabolic diseases at different stages of life.

Is low-protein diet a possible risk factor of malnutrition in chronic kidney disease patients?

Chronic kidney disease (CKD) is becoming increasingly widespread in the world. Slowing its progression means to prevent uremic complications and improve quality of life of patients. Currently, a low-protein diet (LPD) is one of the tools most used in renal conservative therapy but a possible risk connected to LPD is protein-energy wasting. The aim of this study is evaluate the possible correlation between LPD and malnutrition onset. We enrolled 41 CKD patients, stages IIIb/IV according to K-DIGO guidelines, who followed for 6 weeks a diet with controlled protein intake (recommended dietary allowance 0.7 g per kilogram Ideal Body Weight per day of protein). Our patients showed a significant decrease of serum albumin values after 6 weeks of LDP (T2) compared with baseline values (T0) (P=0.039), whereas C-reactive protein increased significantly (T0 versus T2; P=0.131). From body composition analysis, a significant impairment of fat-free mass percentage at the end of the study was demonstrated (T0 versus T2; P=0.0489), probably related to total body water increase. The muscular mass, body cell mass and body cell mass index are significantly decreased after 6 weeks of LDP (T2). The phase angle is significantly reduced at the end of the study compared with basal values (T0 versus T2; P=0.0001, and T1 versus T2; P=0.0015). This study indicated that LPD slows down the progression of kidney disease but worsens patients' nutritional state.

Very-low-calorie ketogenic diet with aminoacid supplement versus very low restricted-calorie diet for preserving muscle mass during weight loss: a pilot double-blind study.

OBJECTIVE: Obesity plays a relevant pathophysiological role in the development of health problems, arising as result of complex interaction of genetic, nutritional and metabolic factors. We conducted a dietary intervention case-control randomized trial, to compare the effectiveness on body composition of two nutritional protocols: a very-low-carbohydrate ketogenic diet (VLCKD), integrated by an aminoacid supplement with whey protein, and very low restricted-calorie diet (VLCD). PATIENTS AND METHODS: The clinical study was conducted with a randomized case-control in which twenty-five healthy subjects gave informed consent to participate in the interventional study and were evaluated for their health and nutritional status, by anthropometric, and body composition evaluation. RESULTS: The results of this pilot study show that a diet low in carbohydrates, associated with a decreased caloric intake, is effective in weight loss. After VLCKD, versus VLCD, no significant differences in body lean of the trunk, body lean distribution (android and gynoid), total body lean were observed (p > 0.05). After VLCKD, no increasing of sarcopenia frequency, according ASSMI, was observed. DISCUSSION: Many studies have shown the effectiveness of the ketogenic diet on weight loss; even if not know how to work effectively, as some researchers believe that the weight loss is due to reduced calorie intake, satiety could also be induced by the effect of the proteins, rather than the low-carbohydrates. CONCLUSIONS: Our pilot study showed that a VLCKD was highly effective in terms of body weight reduction without to induce lean body mass loss, preventing the risk of sarcopenia. Further clinical trials are needed on a larger population and long-term body weight maintenance and risk factors management effects of VLCKD. There is no doubt, however, that a proper dietary approach would impact significantly on the reduction of public expenditure costs, in view of prospective data on increasing the percentage of obese people in our nation.

[Surgical treatment of umbilical hernia in children. Our experience]. / La correzione chirurgica dell'ernia ombelicale in età pediatrica. Esperienza personale.

AIM: To identify the main parameters which, differently correlated, indicate in which case, age and modality umbilical hernia in children should be surgically repaired. METHODS: The authors report personal experience on 319 children with umbilical hernia observed in the last 7 years. In 72 cases, on the basis of the evaluation of some parameters, a surgical correction was performed with the technique described. RESULTS: All the procedures were performed in "day surgery". There were no early complications, neither anesthetic nor surgical. All children showed a good recovery of all functions (feeding, intestinal canalization, walking about) and activities. No middle and long-term complications were observed. CONCLUSIONS: Umbilical hernia needs a surgical repair only in a few cases and after a careful evaluation of some parameters (age, sex, kind of hernia, size and consistency of the hernial porta, protrusion and expansion). The surgical procedure should guarantee either the safe and prompt repair or the cosmetic result; the use of some devices (anesthetic and surgical) allow to obtain excellent results.

[Rectosigmoid junction neoplasms: our experience]. / Le neoplasie della giunzione sigma-retto: esperienze personali.

The Authors report their experience with 25 patients operated for colorectal junction neoplasms from January 1998 to December 2002 in the Section of Oncological Surgery, at Perugia University. According to the international literature, the Authors maintain the absolute functional and anatomical individuality of this part of the large bowel, underlining the peculiarity of the sigmoidal junction neoplasms respect all the others colic sites regarding clinical manifestations, symptoms developing and biological behaviour. The characteristics seem also capable of changing the surgical choice as well as the prognosis of the disease.

Identification of cells secreting a thymostimulin-like substance and examination of some histoenzymatic pathways in aging avian primary lymphatic organs: II. Bursa of Fabricius.

The Bursa of Fabricius of 15 day, 1-, 3-, and 6 month-old adult chickens (White Leghorn strain) were studied by histological and histochemical staining, histoenzymatic reactions (LDH, SDH, a-GPDH, NAD, NADPH, Ca++-dependent ATP-ase, pH 8.5) and by anti-thymostimulin immunoreaction. Positive reactions for mucopolysaccharides and enzymatic activities were located in the epithelia of the follicles, i.e. in follicle-associated-epithelium (FAE), inter-follicle-epithelium (IFE) and in different epithelial compartments of cortical and medullary zones. Positive reaction for thymostimulin-like (TS-like) substance was restricted to FAE cells and weakly to the basal lamina of IFE. In 6-month-old chickens, the FAE cells disappeared; the phenomenon of bursal regression was evident, although not all the follicles were involved. In the few still normal follicles, the good reactivity to the enzymes tested suggests that residual physiological activity is still present, even if reduced.

[The use of surgical endo-prosthesis in the treatment of choledocolithiasis in the elderly. Personal experience]. / L'uso delle endoprotesi chirurgiche nel trattamento della litiasi della VBP nell'anziano. Esperienze personali.

BACKGROUND: The usefulness of biliary endoprostheses in some selected elderly patients affected by hepato-choledocolithiasis is described. METHODS: In the Department of Surgery, University of Perugia, 119 elderly patients were surgically treated for choledocholithiasis from January 1999 to December 2000. In 44 selected cases#151;oldest patients with thinner hypovascularized ectasic choledochal wall#151; a permanent transpapillary polyurethane prosthesis was placed, after choledocolithotomy with or without sphinterotomy; sometimes prosthesis was placed under the duodenal mucosa. RESULTS: Endoprosthesis had a long duration and gave good results in canalization and periprosthetic flow, in absence of biliary stasis and/or angiocholitis. Only one patient had prostheses displacement. CONCLUSIONS: On the basis of personal experience and considering physiopathology and pathogenesis of biliary stones in the elderly, the authors underline, in selected cases, the need of stenting the hepatocholedochal lumen with the aim of avoiding collapse.

Co-localization of multiple ErbB receptors in stratified epithelium of oral squamous cell carcinoma.

The expression of all four ErbB receptors was compared by immunohistochemistry, using receptor-specific polyclonal antisera, in 32 invasive, 11 in situ carcinomas, six benign lesions, and 22 samples of histologically normal mucosa adjacent to specimens of carcinoma originating from oral cavity epithelium. Among invasive and in situ carcinoma, EGFR expression was the most prevalent (in 29/32 and 8/11 cases, respectively) followed by ErbB2 (17/32 and 2/11) and ErbB4 (9/32 and 1/10), while ErbB3 was only detected in invasive tumours (12/32). Specific patterns included invasive tumours with expression of EGFR (8/32) or ErbB4 (1/32) alone, as well as different receptor combinations (EGFR+ErbB2, EGFR+ErbB4, EGFR+ErbB2+ErbB3, EGFR+ErbB2+ErbB4, and all four receptors). Simultaneous expression of three or four ErbB receptors correlated with tumour invasion (p=2.2x10(-4)) and localized in the intermediate epithelial cell layer of well and moderately differentiated tumours. No other significant correlation with clinico-pathological features was noticed. Some benign lesions and histologically normal mucosa adjacent to carcinomas showed weak immunostaining of EGFR (10/28), ErbB2 (4/28) or ErbB4 (3/28). By comparison, overexpression, as indicated by increased staining intensity, was observed in invasive tumours for EGFR (18/32), ErbB2 (8/32), ErbB4 (3/32), and ErbB3 (3/32). Statistical evaluation demonstrated a significant association of EGFR or ErbB2 overexpression with invasive carcinoma when compared with benign lesions and apparently normal epithelium (p=5.2x10(-7) and p=5x10(-3), respectively). Tumour-specific overexpression of ErbB receptors and their co-expression, most frequently involving EGFR and ErbB2, in the same cell layer of neoplastic epithelium, implicate receptor heterodimers in the pathogenesis of oral squamous carcinoma.

Maxillofacial implications and surgical treatment of arthrogryposis multiplex congenita.

A case of arthrogryposis multiplex congenita that affected a patient's temporomandibular joint is described. Preoperatively, the patient's interincisal opening was limited to 9 mm. Elective surgery was performed, which consisted of bilateral coronoidotomies, right and left meninscectomies, capsular release, and lateral pterygoid myotomies. Physical therapy was initiated postoperatively. Eighteen weeks after the surgery, the patient was able to open 18 mm and force open to 20 mm. The patient also noted significant improvement in speech and jaw function in the postoperative period.

ErbB2 immune response in breast cancer patients with soluble receptor ectodomain.

Investigation of ErbB2 immunity in human breast cancer employing recombinant expression sources in immunoblot analysis revealed ErbB2-specific antibodies of the IgG isotype in sera of 14 of 71 cancer patients and 1 of 31 normal donors. Reactivity was confirmed on ErbB2-specific immunoprecipitates. Independent evidence of existing ErbB2 immunity was obtained after in vitro transformation of peripheral blood leukocytes from six positive patients. Furthermore, in vitro immortalization of B-lymphocytes unmasked existent ErbB2 immunity in 1 of 8 patients negative for ErbB2 serum antibodies. Determining shed ErbB2 extracellular domain as an indirect measure of tumor burden in ErbB2-positive malignancy, elevated serum levels were observed in 16 of 71 breast cancer and 1 of 31 normal donor sera. Strikingly, existing ErbB2 immunity correlated significantly with elevated shed ErbB2 ectodomain among the patients analyzed. Incidence of both ErbB2 immunity and elevated ErbB2 extracellular domain increased with a progressed disease stage and was significantly associated with metastatic breast cancer. These observations implicate soluble ErbB2 amounts in vivo in the development of ErbB2 immunity in breast cancer. They further project serum analysis of ErbB2 immunity and soluble ectodomain as potential markers of disease progression in ErbB2-positive malignancy.

Immune responses to all ErbB family receptors detectable in serum of cancer patients.

Employing NIH3T3 transfectants with individual human ErbB receptor coding sequences as recombinant antigen sources, we detected by immunoblot analysis specific immunoreactivity against all four ErbB receptors among 13 of 41 sera obtained from patients with different types of epithelial malignancies. Overall, serum positivity was most frequently directed against ErbB2 followed by EGFR, ErbB3 and ErbB4. Specificity patterns comprised tumor patients with unique serum reactivity against ErbB2 or ErbB4. Moreover, approximately half of the positive sera exhibited concomitant reactivity with multiple ErbB receptors including EGFR and ErbB2, EGFR and ErbB4, ErbB2 and ErbB3 or EGFR, ErbB2 and ErbB3. Serum reactivity was confirmed for the respective ErbB receptors expressed by human tumor cells and corroborated on receptor-specific immunoprecipitates. Positive sera contained ErbB-specific antibodies of the IgG isotype. Representative immunohistochemical analysis of tumor tissues suggested overexpression of ErbB receptors for which serum antibodies were detectable in five of six patients. These findings implicate multiple ErbB receptors including ErbB3 and ErbB4 in addition to EGFR and ErbB2 in primary human cancer. Heterogeneity of natural ErbB-specific responses in cancer patients warrants their evaluation in light of immunotherapeutic approaches targeting these receptors.

[Intestinal invagination in childhood: etiopathogenetic evaluations and details of surgical technique]. / L'invaginazione intestinale in età pediatrica: valutazioni etiopatogenetiche ed accorgimenti di tecnica operatoria.

Intussusception in childhood, especially the idiopathic type, is herein considered. The Authors evaluate some etiopathological aspects on the basis of their experience in 34 patients, and affirm the need of an early and correct diagnosis. They also consider therapeutical management and surgical approach, evaluating local and general conditions of the patient as well as time passed since the onset of symptoms. Finally the importance of an accurate diagnostical examination during the quiescent period and some details of the surgical technique are stressed.

[An update on parathyroid surgery]. / Attualità in tema di chirurgia delle paratiroidi.

The operative management of patients with hyperparathyroidism is controversial. High rates of persistent hypercalcemia and postoperative hypoparathyroidism are seen in multiple hyperplasia and bilateral neck exploration. Patients undergoing unilateral neck exploration with removal of a single parathyroid adenoma have a rapid clearance of PTH which declines within hours after surgery. There is a sensitive immunometric assay (IRMA) for the intact molecule which demonstrates a decline in 15 minutes during surgery. Intraoperative measurement of PTH may be complementary to surgical skill and histopathologic information and may modulate extension of neck exploration.

[Primary biliary peritonitis without perforation in childhood: etiopathogenetic evaluations and 2 case reports]. / Peritoniti biliari primitive senza perforazione in età pediatrica: valutazioni etiopatogenetiche ed osservazioni su due casi clinici.

The Authors review biliary peritonitis. After some evaluations on etiopathogenesis, biliary peritonitis without perforation in childhood is discussed. The rarity of this form is considered as well as etiopathological hypothesis, difficulties of diagnosis and surgical management. Two cases of primary biliary peritonitis without perforation observed and operated in two children are reported.

[Surgery of hyperthyroidism. Personal experience]. / Gli ipertiroidismi di interesse chirurgico. Esperienze personali.

The Authors report their experience in the management of surgical hyperthyroidism, evaluating the different clinical pictures and the possibility of non surgical treatment. Advantages and disadvantages of both hemithyroidectomy and total thyroidectomy, are also described. The Authors conclude affirming their preference for techniques such as total hemithyroidectomy or thyroidectomy in some types of hyperthyroidism.

[Total thyroidectomy with preservation of the parathyroid glands]. / La tiroidectomia totale con conservazione delle paratiroidi.

The operative treatment of thyroid pathology has to be distinguished for benign and malignant pathology. The major complications associated with thyroid surgery are injury to the recurrent laryngeal nerve and hypoparathyroidism. Postoperative hypoparathyroidism is rarely the result of inadvertent removal of all parathyroid glands but, non commonly, is due to disruption of their blood supply. Postoperative hypoparathyroidism results in patients with symptomatic hypocalcemia, transitory and permanent hypoparathyroidism. Subtotal thyroidectomy is used for the treatment of benign thyroid pathology while tumors are treated by total thyroidectomy with neck dissection.

[Advanced gastric cancer in the elderly. Oncologic evaluation & considerations of operative technique]. / Il cancro gastrico in fase avanzata in età geriatrica. Valutazioni oncologiche e considerazioni di tecnica operatoria.

The Authors reviewed their series of 28 consecutive elderly patients operated on for gastric cancer in the Division of General and Oncological Surgery--Department of Surgery and Surgical Emergencies of the University of Perugia from January 1993 to December 1994. Thirteen subtotal gastrectomies associated with resection of the nearby organs in 5 cases, six total gastrectomies, two gastrojejunal bypass, and seven atypical resections of the middle third of the stomach were performed. The Authors focus their attention on this atypical technique pointing out the advantages compared to other procedures as well as criteria for patients selection. Gastric resection of the middle third seems a worthwhile procedure for well selected elderly patients, resulting in a good quality of life with low morbidity and mortality.

[Hemidiaphragmatic reconstruction: the evaluation of 3 clinical cases]. / La ricostruzione dell'emidiaframma: valutazioni su tre casi clinici.

The Authors after a review of the embriology, physiology and pathophysiology of diaphragm, report three cases of congenital or acquired diaphragmatical hernias. They discuss advantages and disadvantages of different surgical techniques on the basis of their technical experience as well as results obtained.

[Gastric cancer in the geriatric patient: our experience]. / Il cancro gastrico nel paziente in età geriatrica: nostra esperienza.

The Authors report their experience in the management of 68 patients aged over 70 years affected by gastric cancer: 64 of them were operated. After some considerations on patients status, nutritional and immunological conditions, operative risk and cancer characteristics the Authors, on the basis of the results obtained, discuss about the opportunity of surgical therapy and relative adequate surgical techniques in the elderly.

Alloplastic reconstruction of the temporomandibular joint.

The Proplast TMJ condylar implant, the glenoid fossa implant, and the TMJ interpositional implants should be singled out as having provided a new and more predictable mode of TMJ reconstruction. The use of these implants in cases of ankylosis, degenerative joint disease, orthognathic deformities, and traumatic injuries has greatly contributed to the success of these reconstructions. These implants represent the state of the art in TMJ reconstruction and increasing data from longer-term follow-up have shown a rate of success much higher than any previous implant used in the TMJ. TMJ reconstruction requires careful surgical planning, meticulous surgical technique, and intelligent perioperative care. Postoperative physical therapy is considered essential in the management of these patients. Complications related to reankylosis have been virtually eliminated, as no postoperative immobilization is required in most cases. Long-term stability of these implants, due to the ingrowth of tissue into Proplast, appears to be assured. Continued experience with the implants and close follow-up of reconstruction patients is necessary in the future to adequately assess the performance of the newer glenoid fossa and TMJ interpositional implants. Certainly, a new era in TMJ reconstruction has begun, resulting in increased benefits to the patients whom we all serve.