Preoperative Prognostic Nutritional Index was not predictive of short-term complications after laparoscopic resection for rectal cancer.

BACKGROUND AND AIM: Prognostic Nutritional Index (PNI) is a useful tool to predict short-term results in patients undergoing surgery for gastrointestinal cancer. Few studies have addressed this issue in colorectal cancer or specifically in rectal cancer. We evaluated the prognostic relevance of preoperative PNI on morbidity of patients undergoing laparoscopic curative resection for rectal cancer (LCRRC). METHODS: PNI data and clinico-pathological characteristics of LCRRC patients (June 2005-December 2020) were evaluated. Patients with metastatic disease were excluded. Postoperative complications were evaluated using the Clavien-Dindo classification. RESULTS: A total of 182 patients were included in the analysis. Median preoperative PNI was 36.5 (IQR 32.8-41.2). Lower PNI was associated with females (p=0.02), older patients (p=0.0002), comorbidity status (p<0.0001), and those who did not receive neoadjuvant treatment (p=0.01). Post-operative complications occurred in 53 patients (29.1%), by the Clavien-Dindo classification: 40 grades I-II and 13 grades III-V. Median preoperative PNI was 35.0 (31.8-40.0) in complicated patients and 37.0 (33.0-41.5) in uncomplicated patients (p=0.09). PNI showed poor discriminative performance regarding postoperative morbidity (AUC 0.57) and was not associated with postoperative morbidity (OR 0.97) at multivariable analysis. CONCLUSIONS: Preoperative PNI was not associated with postoperative morbidity after LCRRC. Further research should focus on different nutritional indicators or hematological/immunological biomarkers.

Prognostic effect of sarcopenia in patients undergoing laparoscopic rectal cancer resection.

BACKGROUND: The importance of body composition, in particular skeletal muscle mass, as risk factor affecting survival of cancer patients has recently gained increasing attention. The relationship between sarcopenia and oncological outcomes has become a topic of research in particular in patients with gastrointestinal cancer. However, there are few studies addressing this issue in colorectal cancer, and even less specifically focused on rectal cancer, in particular in Western countries. The aim of this study was to evaluate the prognostic relevance of preoperative skeletal mass index (SMI) on long-term outcomes in patients undergoing laparoscopic curative resection for rectal cancer. METHODS: SMI data and clinicopathological characteristics of rectal cancer patients in a 15-year period (June 2005-December 2020) were evaluated; patients with metastatic disease at surgery were excluded; overall and disease-free survival as well as recurrence were evaluated. RESULTS: Hundred and sixty-five patients were included in the study. Sarcopenia was identified in 30 (18%) patients. Multivariate analysis identified sarcopenia (HR = 3.28, CI = 1.33-8.11, P = 0.015), along with age (HR = 1.06, CI = 1.02-1.10, P = 0.002) and stage III (HR = 2.63, CI = 1.13-6.08, P < 0.03) as independent risk factors for overall survival. CONCLUSION: Long-term results of rectal cancer patients undergoing curative resection are affected by their preoperative skeletal muscle status. Larger studies including comprehensive data on muscle strength along with SMI are awaited to confirm these results on both Eastern and Western rectal cancer patient populations before strategies to reverse muscle depletion can be extensively applied.

Does 3D laparoscopic video technology affect long-term survival in right hemicolectomy for cancer compared to standard 2D? A propensity score study.

BACKGROUND: There are few studies focused on the short-term results of laparoscopic right hemicolectomy performed with 2D (two-dimension) or 3D (three-dimension) video technology and none on the oncologic effects. The aim of the study was to assess the long-term results of laparoscopic right hemicolectomy (LRH) with intracorporeal anastomosis using 3D or 2D video in patients with right colon cancer with at least three years of oncologic follow-up. METHODS: Data from patients undergoing laparoscopic right hemicolectomy (LRH) with intracorporeal anastomosis for cancer in an 11-year period (June 2008-June 2019) and ≥ 3 years of follow-up were prospectively collected. Surgical procedures were performed by two expert laparoscopic surgeons. RESULTS: 111 patients were included in the study: 56 (50.5%) in the 3D group and 55 (49.5%) in the 2D group. Tumor stage and number of lymph nodes harvested were similar. Overall and disease-free survival were not different in the two groups. Local recurrence occurred in none of the patients, and distant metachronous metastases were similar in the two groups. A propensity score weighting approach was used to account for potential confounding related to patients' nonrandom allocation to the 2 groups. The effects of the intervention on postoperative outcomes were assessed with a weighted regression approach. CONCLUSIONS: Laparoscopic 3D technology allows similar oncological results as 2D vision in LRH with intracorporeal anastomosis. Larger prospective randomized studies might confirm these results in the long-term follow-up.

Nab-paclitaxel/gemcitabine combination is more effective than gemcitabine alone in locally advanced, unresectable pancreatic cancer - A GISCAD phase II randomized trial.

BACKGROUND: The role of combination chemotherapy has not yet been established in unresectable locally advanced pancreatic cancer (LAPC) lacking dedicated randomized trials. METHODS: This phase II trial tested the efficacy of Nab-paclitaxel (NAB-P)/Gemcitabine (G) versus G alone. Patients were randomized, 1:1 to G 1000 mg/m2 on days 1, 8 and 15 every 28 days versus NAB-P 125 mg/m2 on days 1, 8 and 15 every 28 days plus G 1000 mg/m2 on days 1, 8 and 15 every 28 days. Disease progression rate after three cycles of chemotherapy was the primary end-point. Progression-free survival (PFS), overall survival (OS) and response rate were secondary end-points. FINDINGS: A total of124 patients were enrolled. The study showed a reduction of a progressive disease from 45.6% with G to 25.4% with NAB-P/G (P = 0.01) at 3 months. Noteworthy, at 6 months in the G arm, 35.6% of patients present a metastatic spread versus 20.8% in the NAB/G arm. The response rate was 5.3% in the G arm and 27% in the NAB/G arm. Median PFS was 4 months for the G arm and 7 months for the NAB-P/G arm. Median OS was 10.6 in the G arm and 12.7 months in the NAB-P/G arm. One patient died during treatment with G due to a stroke. INTERPRETATION: NAB-P/G reduced the rate of LAPC patients progressing after three cycles of chemotherapy compared with G, especially in terms of distant relapses. It positively affects PFS. To the best of our knowledge, this is the first randomized trial providing evidence that combination chemotherapy is superior to gemcitabine alone in this setting. CLINICALTRIALS. GOV IDENTIFIER: NCT02043730.

Risk factors for metachronous colorectal cancer in Lynch syndrome patients: a registry-based observational mono-institutional study cohort.

BACKGROUND: Risk factors for metachronous colorectal cancer (mCRC) in Lynch Syndrome (LS) patients are essential for colorectal cancer (CRC) treatment strategy to perform not only a curative but also preventive surgery. The aim of this study was to evaluate the risk factors for mCRC development in LS patients to define the patient subset that may benefit an extended curative and preventive surgical resection. METHODS: Patient's clinical history, oncological, molecular and follow-up were collected retrospectively from the Hereditary Digestive Tumors Registry at the National Cancer Institute of Milan. The age-related cumulative risk of mCRC was calculated using the Kaplan-Meier method. Factors significantly associated with mCRC were analyzed with a Cox regression model. Overall and specific competitive risks were also calculated. RESULTS: In a total of 1346 CRC patients, 159 (11.8%) developed a mCRC after a mean follow-up of 138 months from the primary tumor. The independent risk factors reported by a multivariate analysis were: pathogenetic variants in MLH1 and MSH2 (HR 2.96 and 1.91, respectively) and history of colorectal adenomas (HR 1.54); whereas female sex and extended surgery were protective (HR 0.59 and 0.79, respectively). CONCLUSIONS: Among a high-risk population for CRC, in particular LS, an extended surgery may be considered in CRC patients with specific risk factors (MLH1 or MSH2 germline pathogenic variants, history of colorectal adenomas) to reduce the risk of mCRC development.

Toward a better definition of EPCAM deletions in Lynch Syndrome: Report of new variants in Italy and the associated molecular phenotype.

BACKGROUND: Inherited epimutations of Mismatch Repair (MMR) genes are responsible for Lynch Syndrome (LS) in a small, but well defined, subset of patients. Methylation of the MSH2 promoter consequent to the deletion of the upstream EPCAM gene is found in about 1%-3% of the LS patients and represents a classical secondary, constitutional and tissue-specific epimutation. Several different EPCAM deletions have been reported worldwide, for the most part representing private variants caused by an Alu-mediated recombination. METHODS: 712 patients with suspected LS were tested for MMR mutation in our Institute. EPCAM deletions were detected by multiplex ligation-dependent probe amplification (MLPA) and then defined by Long-Range polymerase chain reaction (PCR)/Sanger sequencing. A comprehensive molecular characterization of colorectal cancer (CRC) tissues was carried out by immunohistochemistry of MMR proteins, Microsatellite Instability (MSI) assay, methylation specific MLPA and transcript analyses. In addition, somatic deletions and/or variants were investigated by MLPA and next generation sequencing (NGS). RESULTS: An EPCAM deletion was found in five unrelated probands in Italy: variants c.556-490_*8438del and c.858+1193_*5826del are novel; c.859-1430_*2033del and c.859-670_*530del were previously reported. All probands were affected by CRC at young age; tumors showed MSI and abnormal MSH2/MSH6 proteins expression. MSH2 promoter methylation, as well as aberrant in-frame or out-of-frame EPCAM/MSH2 fusion transcripts, were detected in CRCs and normal mucosae. CONCLUSION: An EPCAM deletion was the causative variant in about 2% of our institutional series of 224 LS patients, consistent with previously estimated frequencies. Early age and multiple CRCs was the main clinical feature of this subset of patients.

Long-term mortality in obese subjects undergoing malabsorptive surgery (biliopancreatic diversion and biliointestinal bypass) versus medical treatment.

BACKGROUND AND AIM: Aim of this study was to analyze long-term mortality in obese patients receiving malabsorptive bariatric surgery (BS)[biliopancreatic diversion (BPD) and biliointestinal bypass (BIBP)] in comparison to medical treatment of obesity. PATIENTS AND METHODS: Medical records of 1877 obese patients [body mass index (BMI) > 35 kg/m2, aged 18-65 years, undergoing BS (n = 472, 111 with diabetes) or non-surgical medical treatment (n = 1405, 385 with diabetes), during the period 1999-2008 (visit 1)] were collected; non-surgical patients were matched for age, sex, BMI, and blood pressure, and life status and causes of death were ascertained through December 2016. Survival was compared across surgery patients and non-surgical patients using Kaplan-Meier plots and Cox regression analyses. RESULTS: Observation period was 12.1 ± 3.41 years (mean ± SD). Compared to non-surgical patients, BS patients had reduced all-cause mortality (34/472 (7.2%) vs 181/1,405 (12.9%) patients, χ2 = 11.25, p = 0.001; HR = 0.64, 95% C.I. 0.43-0.93, p = 0.019). Cardiovascular and cancer causes of death were significantly less frequent in surgery vs no-surgery (HR = 0.26, 95% C.I. 0.09-0.72, p = 0.003; HR = 0.21, 95% C.I. 0.09-0.45, p < 0.001, respectively). CONCLUSION: Patients who have undergone BPD and BIBP have lower long-term all-cause, cardiovascular-caused and cancer-caused mortality compared to non-surgical medical weight-loss treatment patients. Malabsorptive bariatric surgery significantly reduces long-term mortality in severely obese patients.

Performance of tumor testing for Lynch syndrome identification in patients with colorectal cancer: A retrospective single-center study.

OBJECTIVE:: To investigate the performance of tumor testing approaches in the identification of Lynch syndrome (LS) in a single-center cohort of people with colorectal cancer (CRC). METHODS:: A retrospective analysis of data stored in a dedicated database was carried out to identify patients with CRC suspected for LS who were referred to Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, between 1999 and 2014. The sensitivity and specificity of immunohistochemistry (IHC) for mismatch repair (MMR) proteins and microsatellite instability (MSI) analysis (alone or combined) were calculated with respect to the presence of causative MMR germline variants. RESULTS:: A total of 683 patients with CRC suspected for LS were identified. IHC results of MMR protein analysis and MSI were assessed in 593 and 525 CRCs, respectively, while germline analysis was performed in 418 patients based on the IHC or MSI test result and/or clinical features. Univariate and multivariate analysis revealed a significant correlation of pathogenic MMR germline variants with all clinicopathologic features including Amsterdam criteria, presence of endometrial cancer, CRC site, age at onset, stage, and grade. The highest odds ratio values were observed for IHC and MSI (17.1 and 8.8, respectively). The receiver operating characteristic curve and area under the curve values demonstrated that IHC alone or combined with other clinicopathologic parameters was an excellent test for LS identification. CONCLUSIONS:: This study confirms the effectiveness of tumor testing to identify LS among patients with CRC. Although IHC and MSI analysis were similarly effective, IHC could be a better strategy for LS identification as it is less expensive and more feasible.

Laparoscopic Curative Resection for Rectal Cancer: A Cohort Study on Long-term Outcome.

The aim of the present study was to evaluate the long-term results of laparoscopic curative resection for rectal cancer. We included all patients who underwent laparoscopic curative resection for rectal cancer from June 2005 to September 2015. A total of 159 patients were included; 33.9% received neoadjuvant chemoradiotherapy. Thirty-day mortality and morbidity rates were 0.6% and 26.4%, respectively. Pathologic stage was 0 in 12%, I in 39%, II in 24.5%, and III in 24.5%. The median number of lymph nodes harvested was 16. In 5% of patients, mesorectal excision was incomplete. Median follow-up was 59 months. Overall 5-year survival was 80%. Multivariable analysis identified older age, higher Charlson Comorbidity Index, advanced tumor stage, and postoperative morbidity as independent risk factors for overall/disease-free survival. Local/distant recurrence rate was 4.4%/17.6%. Deaths during follow-up were 33/159 (20.8%): cancer related 54.6% and non cancer related 45.4% of patients. Laparoscopic curative resection for rectal cancer can yield prolonged survival and low recurrence.

New concepts on the clinical course and stratification of compensated and decompensated cirrhosis.

The clinical course of cirrhosis has been typically described by a compensated and a decompensated state based on the absence or, respectively, the presence of any of bleeding, ascites, encephalopathy or jaundice. More recently, it has been recognized that increasing portal hypertension and several major clinical events are followed by a marked worsening in prognosis, and disease states have been proposed accordingly in a multistate model. The development of multistate models implies the assessment of the probabilities of more than one possible outcome from each disease state. This requires the use of competing risks analysis which investigates the risk of several competing outcomes. In such a situation, the Kaplan-Meier risk estimates and the Cox regression may be not appropriate. Clinical states of cirrhosis presently considered as suitable for a comprehensive multistate model include: in compensated cirrhosis, early (mild) portal hypertension with hepatic venous pressure gradient (HVPG) >5 and <10 mmHg, clinically significant portal hypertension (HVPG ≥ 10 mmHg) without gastro-esophageal varices (GEV), and GEV; in decompensated cirrhosis, a first variceal bleeding without other decompensating events, any first non-bleeding decompensation and any second decompensating event; and in a late decompensation state, refractory ascites, sepsis, renal failure, recurrent encephalopathy, profound jaundice, acute on chronic liver failure, all predicting a very short survival. In this review, we illustrate how competing risks analysis and multistate models may be applied to cirrhosis.

Clinical states of cirrhosis and competing risks.

The clinical course of cirrhosis is mostly determined by the progressive increase of portal hypertension, hyperdynamic circulation, bacterial translocation and activation of systemic inflammation. Different disease states, encompassing compensated and decompensated cirrhosis and a late decompensated state, are related to the progression of these mechanisms and may be recognised by haemodynamic or clinical characteristics. While these disease states do not follow a predictable sequence, they correspond to varying mortality risk. Acute-on-chronic liver failure may occur either in decompensated or in compensated cirrhosis and is always associated with a high short-term mortality. The increasing severity of these disease states prompted the concept of clinical states of cirrhosis. A multistate approach has been considered to describe the clinical course of the disease. Such an approach requires the assessment of the probabilities of different outcomes in each state, which compete with each other to occur first and mark the transition towards a different state. This requires the use of competing risks analysis, since the traditional Kaplan-Meier analysis should only be used in two-state settings. Accounting for competing risks also has implications for prognosis and treatment efficacy research. The aim of this review is to summarise relevant clinical states and to show examples of competing risks analysis in multistate models of cirrhosis.

Not ery small bowel submucosal mass is a GIST A rare case of small bowel schwannoma.

INTRODUCTION: Schwannomas are slow-growing tumors, rarely occurring in the GI tract. When found, their location is mostly in the stomach. Presentation in the small bowel is extremely rare, anecdotal. CASE REPORT: We present the case of a 47-year old male who underwent laparoscopic elective left hemicolectomy for recurrent diverticulitis. RESULTS: At surgery an exophytic mass originating from the first jejunal loop was identified and resected, under the suspicion of a GIST. Post-operative pathologic report was consistent with the diagnosis of jejunal schwannoma. Unfortunately resection margins were positive and the patient was taken back to the OR for an additional jejunal segmental resection. CONCLUSIONS: GI schwannomas have excellent prognosis after surgical resection. It is important to differentiate them from GISTs, which may have a malignant behavior in 10-30% of the cases. To ensure complete surgical resection with negative margins is mandatory and is the curative treatment of choice. KEY WORDS: GIST, Jejunum, Submucosa Minimally-invasive surgery, Schwannoma, Small bowel.

Long-term mortality and incidence of cardiovascular diseases and type 2 diabetes in diabetic and nondiabetic obese patients undergoing gastric banding: a controlled study.

BACKGROUND AND AIM: Aim of this retrospective study was to compare long-term mortality and incidence of new diseases [diabetes and cardiovascular (CV) disease] in morbidly obese diabetic and nondiabetic patients, undergoing gastric banding (LAGB) in comparison to medical treatment. PATIENTS AND METHODS: Medical records of obese patients [body mass index (BMI) > 35 kg/m(2) undergoing LAGB (n = 385; 52 with diabetes) or medical treatment (controls, n = 681; 127 with diabetes), during the period 1995-2001 (visit 1)] were collected. Patients were matched for age, sex, BMI, and blood pressure. Identification codes of patients were entered in the Italian National Health System Lumbardy database, that contains life status, causes of death, as well as exemptions, drug prescriptions, and hospital admissions (proxies of diseases) from visit 1 to September 2012. Survival was compared across LAGB patients and matched controls using Kaplan-Meier plots adjusted Cox regression analyses. RESULTS: Observation period was 13.9 ± 1.87 (mean ± SD). Mortality rate was 2.6, 6.6, and 10.1 % in controls at 5, 10, and 15 years, respectively; mortality rate was 0.8, 2.5, and 3.1 % in LAGB patients at 5, 10, and 15 years, respectively. Compared to controls, surgery was associated with reduced mortality [HR 0.35, 95 % CI 0.19-0.65, p < 0.001 at univariate analysis, HR 0.41, 95 % CI 0.21-0.76, p < 0.005 at adjusted analysis], similar in diabetic [HR 0.34, 95 % CI 0.13-0.87, p = 0.025] and nondiabetic [HR 0.42, 95 % CI 0.19-0.97, p = 0.041] patients. Surgery was also associated with lower incidence of diabetes (15 vs 48 cases, p = 0.035) and CV diseases (52 vs 124 cases, p = 0.048), and of hospital admissions (88 vs 197, p = 0.04). CONCLUSION: Up to 17 years, gastric banding is associated with reduced mortality in diabetic and nondiabetic patients, and with reduced incidence of diabetes and cardiovascular diseases.

Outcomes of Chopart Amputation in a Tertiary Referral Diabetic Foot Clinic: Data From a Consecutive Series of 83 Hospitalized Patients.

The purpose of the present retrospective study was to evaluate the outcomes (ie, ulcer recurrence, major amputation, death) in diabetic patients undergoing Chopart amputation because of deep infection or gangrene extending to the midfoot. From 2009 to 2011, 83 patients, aged 71.4 ± 9.3 years, underwent a midtarsal amputation and were followed up until December 31, 2012 (mean follow-up 2.8 ± 0.8 years). Of the 83 patients, 26 were female, 61 required insulin, 47 had renal insufficiency, 19 underwent hemodialysis, 65 had hypertension, 34 had a history of cardiac disease, and 4 had a history of stroke. Chopart amputation was performed in 38 patients (45.8%) with gangrene, 31 (37.4%) with abscess, and 14 (16.9%) with osteomyelitis. Urgent surgery was performed in 56 patients (67.5%). Effective revascularization was performed in 64 patients (77.1%) patients. Of the 83 patients, 47 had healed at a mean period of 164.7 (range 11 to 698) days. Ulcer recurrence developed in 15 patients (31.9%). A major amputation was necessary in 23 patients (27.7%), with an annual incidence of 13.0%. None of the included variables on logistic regression analysis was significantly associated with proximal amputation. Of the 83 patients, 38 (45.8%) died, with an annual incidence of 25.8%. On logistic regression analysis, age (odds ratio [OR] 1.11, 95% confidence interval [CI] 1.01 to 1.16), history of stroke (OR 9.94, 95% CI 3.16 to 31.24), and urgent surgery (OR 2.60, 95% CI 1.14 to 5.93) were associated with mortality. Chopart amputation represents the last chance to avoid major amputation for diabetic patients with serious foot complications. Our success rate was great enough to consider Chopart amputation a viable option for limb salvage in this high-risk population.

Long-Term Follow-Up of UCLP Patients: Surgical and Orthodontic Burden of Care During Growth and Final Orthognathic Surgery Need.

OBJECTIVE: The goal of this study was to evaluate the craniofacial morphology at 5 and 10 years of age and at the completion of growth, the need for final orthognathic surgery, and the orthodontic burden in a sample of patients with unilateral cleft lip and palate consecutively treated by the same surgeon with the same two-step protocol. DESIGN: A sample of 62 adult patients with unilateral cleft lip and palate was retrospectively collected (mean age, 17.5 years). Lateral cephalograms at three time points were traced. The need for orthognathic surgery was assessed, subdividing the sample into an orthognathic surgery group and nonorthognathic surgery group. Time and modality of orthodontic treatment were recorded. RESULTS: Cephalometric values related to maxillary growth (SNA, SNAns) and maxillomandibular relation (ANB, NAPg) were significantly different between the two groups already at 5 and 10 years of age. All patients presenting an ANB smaller than 2° at 5 years needed a Le Fort I osteotomy. Mandibular protrusion (SNB, SNPg) was not different at 5 and 10 years, but was different at the completion of growth. Patients with the same initial maxillomandibular relation did not show better growth when subjected to earlier or longer orthodontic treatment. CONCLUSION: Patients needing final jaw surgery had a more severe skeletal discrepancy during early childhood. The ANB angle at 5 years allowed doctors to identify 45% of the need for orthognathic surgery. The final craniofacial pattern does not seem to change significantly with early or prolonged orthodontic treatment.

Multimodality treatment of osteosarcoma of the jaw: a single institution experience.

Osteosarcomas of the jaws are rare mesenchymal tumors frequently diagnosed in the fourth decade of life which account for 6 % of all osteosarcomas. This study evaluated the efficacy on the patients outcome of multimodality treatment consisting of surgery, chemotherapy and radiotherapy. The records of 22 patients affected by jaw osteosarcoma treated with a combination of surgery, poly-chemotherapy and adjuvant radiotherapy in selected cases were reviewed. Response rate, progression-free survival and overall survival were evaluated. Neoadjuvant chemotherapy resulted in an overall response rate of 83.3 %, necrosis of grade I or II was obtained, respectively, in 44.4 and 55.6 % of the patients, and surgery was radical in all patients. At a median follow-up of 60 months, the 5-year progression-free survival and overall survival were 73.5 and 77.4 %, respectively. These outcome parameters significantly correlated with age at diagnosis and grade of chemotherapy-induced necrosis. A complex multimodality approach including chemotherapy and radiotherapy, along with radical surgery, can maximize the outcome of patients affected by osteosarcoma of the jaws.

Prevention of type 2 diabetes in obese at-risk subjects: a systematic review and meta-analysis.

Different intervention strategies can prevent new cases of type 2 diabetes (T2DM) in obese subjects. The present systematic review and meta-analysis evaluates the effectiveness of different strategies in prevention of type 2 diabetes in obese subjects. Studies were grouped into five different strategies: (1) physical activity ± diet; (2) anti-diabetic drugs (glitazones, metformin, glinides, alfa-glucosidase inhibitors); (3) antihypertensive drugs (ACE inhibitors, ARB); (4) weight loss-promoting drugs and lipid-lowering drugs (orlistat, bezafibrate, phentermine/topiramate controlled release); and (5) bariatric surgery. Only controlled studies, dealing with subjects BMI ≥ 30 kg/m(2), were included in the analysis, whether randomized or non-randomized studies. Appropriate methodology (PRISMA statement) was adhered to. Publication bias was formally assessed. Eighteen studies (43,669 subjects, 30,774 with impaired glucose tolerance and/or impaired fasting glucose), published in English language as full papers, were analyzed to identify predictors of new cases of T2DM and were included in a meta-analysis (random-effects model) to study the effect of different strategies. Intervention effect (new cases of diabetes) was expressed as odds ratio (OR), with 95 % confidence intervals (CIs). In obese subjects, non-surgical strategies were able to prevent T2DM, with different effectiveness [OR from 0.44 (0.36-0.52) to 0.86 (0.80-0.92)]; in morbidly obese subjects, bariatric surgery was highly effective [OR = 0.10 (0.02-0.49)]. At meta-regression analysis, factors associated with effectiveness were weight loss, young age and fasting insulin levels. Publication bias was present only when considering all studies together. These data indicate that several strategies, with different effectiveness, can prevent T2DM in obese subjects.

Severity of demographic and clinical characteristics, revascularization feasibility, major amputation, and mortality rate in diabetic patients admitted to a tertiary diabetic foot center for critical limb ischemia: comparison of 2 cohorts recruited at a 10-year distance.

BACKGROUND: To compare demographic and clinical characteristics, revascularization, major amputation, and mortality among patients admitted to a diabetic foot center because of critical limb ischemia (CLI) during 1999-2003 (cohort 1) and 2009 (cohort 2). METHODS: During 1999-2003, 564 diabetic patients with CLI (cohort 1) were admitted to our center, and 344 patients (360 affected limbs) were admitted during 2009 (cohort 2). Data on demographic and clinical characteristics, revascularization by peripheral angioplasty (PTA) or bypass graft (BPG), major amputation, and mortality were recorded. RESULTS: Patients belonging to cohort 2 were older than patients of cohort 1 (P = 0.001). In cohort 2, there were more subjects requiring insulin (P = 0.008) and duration of diabetes was longer (P = 0.001); moreover, there were more patients requiring dialysis (P = 0.001), patients with history of stroke (P = 0.004), or foot ulcer (P = 0.001). No significant difference between the 2 groups was found concerning gender, metabolic control, hypertension, lipid values, neuropathy, and retinopathy. Occlusion was more frequent than stenosis in the posterior tibial (P < 0.001) and peroneal (P = 0.016) arteries. However, the revascularization rate did not differ (P = 0.318) between the 2 groups. Restenosis after PTA was not significantly different (P = 0.627), whereas BPG failure was significantly more frequent (P = 0.010) in cohort 2 (2009). Major amputation (P = 0.222) and mortality rate (P = 0.727) did not differ between the 2 groups. CONCLUSIONS: The severity of either foot lesions or patients comorbidities should be concomitantly assessed and taken into proper consideration when evaluating changes in the amputation rate among different studies or in different temporal settings.

Effectiveness of combined therapy with angiotensin-converting enzyme inhibitors and statins in reducing mortality in diabetic patients with critical limb ischemia: an observational study.

AIMS: To investigate the effect of combined treatment with angiotensin-converting enzyme inhibitors (ACE) and statins on mortality in diabetic patients with critical limb ischemia (CLI). METHODS: Prospective observational study of 553 consecutive diabetic patients admitted because of CLI followed for a mean of 2.2 years. All patients underwent peripheral revascularization and antithrombotic therapy was prescribed or continued and therapy with statin and ACE was recorded. Mortality from any cause was assessed and Kaplan-Meier analyses were performed to compare the relationship between survival and recorded variables. RESULTS: One hundred thirty-nine patients did not have therapy with statin or an ACE, 78 had therapy with statin without ACE, 164 had therapy with ACE without statin and 172 patients had therapy with both statin and ACE. One hundred thirty-six patients died, 45/139 with neither statin nor ACE, 40/164 with ACE only, 26/78 with statin only, and 25/172 with both statin and ACE. Multivariate analysis confirmed the independent role of age, history of stroke, renal insufficiency and dialysis. Combined treatment with ACE and statin appeared to have a protective role. CONCLUSIONS: In patients with diabetes and CLI mortality after two years is high. Life expectancy was better in patients receiving combined therapy with ACE and statin but not with therapy with only a statin or an ACE.

Female sexual dysfunction and diabetes: a systematic review and meta-analysis.

INTRODUCTION: Sexual dysfunction is reported in diabetic women (female sexual dysfunction [FSD]). AIM: To examine the frequency of FSD in diabetic women, and its clinical or metabolic correlates, through meta-analysis of available studies. METHODS: We searched in MEDLINE, EMBASE, Cochrane Library, and in reference lists of articles and systematic reviews; we considered human clinical studies published as full articles reporting on FSD in diabetic and control women. In total, we considered 26 studies, including 3,168 diabetic and 2,823 control women. MAIN OUTCOME MEASURES: Frequency of FSD and score of Female Sexual Function Index (FSFI) as a function of study size, patient details (age, body mass index [BMI], duration of diabetes, metabolic control [HbA1c], chronic complications, Beck Depression Inventory [BDI] score). RESULTS: Frequency of FSD was higher in type 1 (OR [95%CI] 2.27 [1.23, 4.16]), in type 2 diabetes (2.49 [1.55, 3.99]), and in "any diabetes" (type 1 and 2) women (2.02 [1.49, 2.72]) than in controls for any duration of diabetes. FSFI was lower in type 1 (-0.27 [-0.41, -0.12]), in type 2 diabetes (-0.65 [-0.75, -0.54]), and in "any diabetes" women (-0.80 [-0.88, -0.71]) than in controls. Depression was significantly more frequent in diabetic than in control women. At meta-regression only BMI was significantly associated with effect size (P = 0.005). At weighed regression, the only significant association was found between age and FSFI (P = 0.059). The limitations were as follows: only studies of observational nature were available, and heterogeneity was seen among studies. CONCLUSIONS: FSD is more frequent in diabetic than in control women, but it is still poorly understood; low FSFI is associated with high BMI. Further studies are necessary to better understand risk factors for FSD in diabetic women.