Gallbladder Findings after Cholecystectomy in Morbidly Obese Patients

Morbidly obese patients constitute a high risk group for the development of gallbladder disease. In our series 70 consecutive patients underwent vertical gastroplasty in an effort to manage morbid obesity. The mean age was 37 years (range 20-60), and the mean excess body weight was 92 kg (range 52-265). Six patients (8.5%) had undergone cholecystectomy before bariatric surgery because of symptomatic cholelithiasis. The remaining 64 patients underwent cholecystectomy at the time of vertical gastroplasty. Ninety-seven percent of the removed gallbladders had gross or histologic abnormalities, including cholelithiasis 18.5% (13 patients), and cholesterolosis 31% (22 patients). Histologically, chronic cholecystitis was present in all patients with cholelithiasis and cholesterolosis. Chronic cholecystitis alone was found in 27 patients (38.5%) and only two patients (3%) had normal findings. The mean excess body weight of the patients with cholesterolosis (96 kg) was not significantly greater than that of patients with cholelithiasis (89 kg) or chronic cholecystitis (88 kg). Our findings suggest that cholecystectomy should be performed in all morbidly obese patients concomitant with vertical gastroplasty.     

Vertical Banded Gastroplasty Versus Standard or Distal Roux-en-Y Gastric Bypass Based on Specific Selection Criteria in the Morbidly Obese: Preliminary Results

Background: Predicting successful outcomes after bariatric surgical procedures has been difficult, and the establishment of specific selection criteria has been a subject of ongoing research. In an effort to choose the most appropriate surgical procedure for each patient, we have established a specific set of selection criteria for each procedure based on degree of obesity, preoperative dietary habits, eating behavior, and various metabolic features. Methods: From June 1994 to December 1998, 90 bariatric surgical procedures were performed at the authors' institution by a single surgeon (F.K.) based on specific selection criteria. Vertical banded gastroplasty (VBG) was performed in 35 patients, standard Roux-en-Y gastric bypass (RYGB) in 38 patients, and distal RYGB in 17 patients. All patients were monitored postoperatively 1, 3, 6, and 12 months and once per year thereafter, with an additional visit at 18 months in distal RYGB patients. Results: Early postoperative morbidity (<30 days) did not differ significantly between the three groups and averaged 9% of total patients. Long-term postoperative morbidity (>30 days) included 9 incisional hernias (2 in the VBG group, 5 after RYGB, and 2 in the distal RYGB group). There were 6 cases of staple-line disruption, 4 after VBG and 2 after standard RYGB, 1 of which resulted in stomal ulcer. Early postoperative mortality was 0%, and long-term mortality was 1.1%, which was due to pulmonary embolism in 1 standard RYGB patient on the 65th postoperative day. Average percentage of excess weight loss (%EWL) was 62% the first year, 61% the second year, and 50% the third year in VBG patients, and 63.6%, 65%, and 63.3%, respectively, in standard RYGB patients. In distal RYGB patients, where the patient number was significantly smaller, the %EWL at 1 and 2 years, respectively, was 51% and 53%. The most significant metabolic/nutritional complication was the appearance of hypoproteinemia (hypoalbuminemia) in 1 distal RYGB patient 20 months after surgery, which was corrected by total parenteral nutrition and subsequent increase in dietary protein intake. Significant improvement or resolution of pre-existing comorbid conditions was observed in all patient groups. The postoperative quality of eating, as evaluated by variety of food intake and frequency of vomiting, was significantly better in RYGB patients. Conclusions: These results show that selection of the bariatric surgical procedure to be performed in each patient based on specific criteria leads to acceptable weight loss, improvement in preexisting comorbid conditions, and a high degree of patient satisfaction in most patients. On the basis of our own observations as well as those of others, our selection criteria have become more strict over time and our selection of VBG as the operation of choice increasingly infrequent.     

Osteonecrosis of the jaw in cancer after treatment with bisphosphonates: incidence and risk factors.

PURPOSE: Osteonecrosis of the jaw (ONJ) has been associated recently with the use of pamidronate and zoledronic acid. We studied the incidence, characteristics, and risk factors for the development of ONJ among patients treated with bisphosphonates for bone metastases. PATIENTS AND METHODS: ONJ was assessed prospectively since July 2003. The first bisphosphonate treatment among patients with ONJ was administered in 1997. Two hundred fifty-two patients who received bisphosphonates since January 1997 were included in this analysis. RESULTS: Seventeen patients (6.7%) developed ONJ: 11 of 111 (9.9%) with multiple myeloma, two of 70 (2.9%) with breast cancer, three of 46 (6.5%) with prostate cancer, and one of 25 (4%) with other neoplasms (P = .289). The median number of treatment cycles and time of exposure to bisphosphonates were 35 infusions and 39.3 months for patients with ONJ compared with 15 infusions (P < .001) and 19 months (P = .001), respectively, for patients with no ONJ. The incidence of ONJ increased with time to exposure from 1.5% among patients treated for 4 to 12 months to 7.7% for treatment of 37 to 48 months. The cumulative hazard was significantly higher with zoledronic acid compared with pamidronate alone or pamidronate and zoledronic acid sequentially (P < .001). All but two patients with ONJ had a history of dental procedures within the last year or use of dentures. CONCLUSION: The use of bisphosphonates seems to be associated with the development of ONJ. Length of exposure seems to be the most important risk factor for this complication. The type of bisphosphonate may play a role and previous dental procedures may be a precipitating factor.     

Targeting the Platelet-Activating Factor Receptor (PAF-R): Antithrombotic and Anti-Atherosclerotic Nutrients

Platelet-activating factor (PAF) is a lipid mediator that interacts with its receptor (PAF-R) to carry out cell signalling. However, under certain conditions the binding of PAF to PAF-R leads to the activation of pro-inflammatory and prothrombotic pathways that have been implicated in the onset and development of atherosclerotic cardiovascular diseases (CVD) and inflammatory diseases. Over the past four decades, research has focused on the identification and development of PAF-R antagonists that target these inflammatory diseases. Research has also shown that dietary factors such as polar lipids, polyphenols, and other nutrient constituents may affect PAF metabolism and PAF-R function through various mechanisms. In this review we focus on the inhibition of PAF-R and how this may contribute to reducing cardiovascular disease risk. We conclude that further development of PAF-R inhibitors and human studies are required to investigate how modulation of the PAF-R may prevent the development of atherosclerotic cardiovascular disease and may lead to the development of novel therapeutics.     

PROTEIN AI Advisor: A Knowledge-Based Recommendation Framework Using Expert-Validated Meals for Healthy Diets

AI-based software applications for personalized nutrition have recently gained increasing attention to help users follow a healthy lifestyle. In this paper, we present a knowledge-based recommendation framework that exploits an explicit dataset of expert-validated meals to offer highly accurate diet plans spanning across ten user groups of both healthy subjects and participants with health conditions. The proposed advisor is built on a novel architecture that includes (a) a qualitative layer for verifying ingredient appropriateness, and (b) a quantitative layer for synthesizing meal plans. The first layer is implemented as an expert system for fuzzy inference relying on an ontology of rules acquired by experts in Nutrition, while the second layer as an optimization method for generating daily meal plans based on target nutrient values and ranges. The system’s effectiveness is evaluated through extensive experiments for establishing meal and meal plan appropriateness, meal variety, as well as system capacity for recommending meal plans. Evaluations involved synthetic data, including the generation of 3000 virtual user profiles and their weekly meal plans. Results reveal a high precision and recall for recommending appropriate ingredients in most user categories, while the meal plan generator achieved a total recommendation accuracy of 92% for all nutrient recommendations.     

Immunotherapy for advanced hepatocellular carcinoma: From clinical trials to real-world data and future advances

Hepatocellular carcinoma (HCC) is a leading cause of cancer-associated mortality worldwide. HCC is an inflammation-associated immunogenic cancer that frequently arises in chronically inflamed livers. Advanced HCC is managed with systemic therapies; the tyrosine kinase inhibitor (TKI) sorafenib has been used in 1^st-line setting since 2007. Immunotherapies have emerged as promising treatments across solid tumors including HCC for which immune checkpoint inhibitors (ICIs) are licensed in 1^st- and 2^nd-line treatment setting. The treatment field of advanced HCC is continuously evolving. Several clinical trials are investigating novel ICI candidates as well as new ICI regimens in combination with other therapeutic modalities including systemic agents, such as other ICIs, TKIs, and anti-angiogenics. Novel immunotherapies including adoptive cell transfer, vaccine-based approaches, and virotherapy are also being brought to the fore. Yet, despite advances, several challenges persist. Lack of real-world data on the use of immunotherapy for advanced HCC in patients outside of clinical trials constitutes a main limitation hindering the breadth of application and generalizability of data to this larger and more diverse patient cohort. Consequently, issues encountered in real-world practice include patient ineligibly for immunotherapy because of contraindications, comorbidities, or poor performance status; lack of response, efficacy, and safety data; and cost-effectiveness. Further real-world data from high-quality large prospective cohort studies of immunotherapy in patients with advanced HCC is mandated to aid evidence-based clinical decision-making. This review provides a critical and comprehensive overview of clinical trials and real-world data of immunotherapy for HCC, with a focus on ICIs, as well as novel immunotherapy strategies underway.     

Acute myeloid leukemia: negative prognostic impact of early blast persistence can be in part overcome by a later remission prior to post-induction therapy

In acute myeloid leukemia, there is an ongoing debate on the prognostic value of the early bone marrow assessment in patients receiving intensive therapy. In this retrospective study, we analyzed the prognostic impact of the early response in 1,008 patients with newly diagnosed acute myeloid leukemia, who were treated at our institution with intensive chemotherapy followed by consolidation chemotherapy and/or allogeneic hematopoietic stem cell transplantation (HSCT). We found that early blast persistence has an independent negative prognostic impact on overall survival, event-free survival and relapse-free survival. This negative prognostic impact may only be overcome in patients showing at least a partial remission at the early bone marrow assessment and who subsequently achieve blast clearance by additional induction chemotherapy prior to consolidation therapy with allogeneic HSCT. In accordance, we propose that the time slope of remission is an additional leukemia-related dynamic parameter that reflects chemosensitivity and thus may inform post-induction therapy decision-making. In addition to patient-related factors, European LeukemiaNet risk group, measurable residual disease monitoring and donor availability, this may particularly apply to European LeukemiaNet intermediate-risk patients, for whom a decision between consolidation chemotherapy and allogeneic HSCT remains challenging in many cases.