Lipoprotein insulin resistance score in nondiabetic patients with obesity after bariatric surgery

BackgroundLipoprotein insulin resistance (LPIR) score is a composite biomarker representative of atherogenic dyslipidemia characteristic of early insulin resistance. It is elevated in obesity and may provide information not captured in glycosylated hemoglobin and homeostatic model assessment for insulin resistance. While bariatric surgery reduces diabetes incidence and resolves metabolic syndrome, the effect of bariatric surgery on LPIR is untested.ObjectivesWe sought to assess the effects of Roux-en-Y gastric bypass and sleeve gastrectomy on LPIR in nondiabetic women with obesity.SettingNonsmoking, nondiabetic, premenopausal Hispanic women, age ≥18 years, undergoing Roux-en-Y gastric bypass or sleeve gastrectomy at Bellevue Hospital were recruited for a prospective observational study.MethodsAnthropometric measures and blood sampling were performed preoperatively and at 6 and 12 months postoperatively. LPIR was measured by nuclear magnetic resonance spectroscopy.ResultsAmong 53 women (Roux-en-Y gastric bypass, n = 22; sleeve gastrectomy, n = 31), mean age was 32 ± 7 years and body mass index 44.1 ± 6.4 kg/m². LPIR was reduced by 35 ± 4% and 46 ± 4% at 6 and 12 months after surgery, respectively, with no difference by procedure. Twenty-seven of 53 patients met International Diabetes Federation criteria for metabolic syndrome preoperatively and had concomitant higher homeostatic model assessment for insulin resistance, glycosylated hemoglobin, nonhigh-density lipoprotein-cholesterol and LPIR. Twenty-five of 27 patients experienced resolution of metabolic syndrome postoperatively. Concordantly, the preoperative differences in homeostatic model assessment for insulin resistance, glycosylated hemoglobin, and nonhigh-density lipoprotein-cholesterol between those with and without metabolic syndrome resolved at 6 and 12 months. In contrast, patients with metabolic syndrome preoperatively exhibited greater LPIR scores at 6 and 12 months postoperatively.ConclusionThis is the first study to demonstrate improvement in insulin resistance, as measured by LPIR, after bariatric surgery with no difference by procedure. This measure, but not traditional markers, was persistently higher in patients with a preoperative metabolic syndrome diagnosis, despite resolution of the condition.     

Granzyme A — Immunoreactive cells in synovial fluid in reactive and rheumatoid arthritis

Summary Perforin and granzyme A co-localize in the cytotoxic granules of killer cells like cytotoxic T lymphocytes (CTL). Perforin is the cytolytic pore-forming protein, whereas the function of the homodimeric serine protease granzyme A and other members of the granzyme family is still unclear. Granzyme A — immunoreactive cells formed 8±2% of the resting peripheral blood lymphocytes of healthy individuals. In contrast, granzyme A-positive cells formed 15% of peripheral blood mononuclear cells in patients with reactive or rheumatoid arthritis. However, 29±4% (p<0.05 compared to normal peripheral blood) and 25±4% (p<0.05) of all lymphocytes in synovial fluid in reactive and rheumatoid arthritis, respectively, were granzyme A — positive. This suggests involvement of cell-mediated cytolytic mechanisms in the articular pathogenic mechanisms. This involvement, however, does not differentiate between reactive and rheumatoid arthritis.     

Activities of Daily Living and Outcomes in Patients with Advanced Heart Failure

BackgroundFunctional debility is associated with worse outcomes in the general heart failure population, but the prevalence of difficulty with activities of daily living and clinical significance once patients develop advanced heart failure requires further examination.MethodsThis was a population-based, retrospective cohort study of Olmsted County, Minnesota adults with advanced heart failure from 2007-2018. Difficulty with 9 activities of daily living was assessed by questionnaire. Predictors of difficulty were assessed by a proportional odds model. Associations of difficulty with activities of daily living with mortality and hospitalization were examined using Cox and Andersen-Gill models.ResultsAmong 765 patients with advanced heart failure, 565 (73.9%) reported difficulty with activities of daily living at diagnosis. Of those, 257 (45%) had moderate and 148 (26%) had severe difficulty. Independent predictors of difficulty included female sex (odds ratio [OR] 1.73; 95% confidence interval [CI], 1.26-2.36; P = .001), older age (OR per 10-year increase 1.17; 95% CI, 1.05-1.31; P = .005), dementia (OR 1.85; 95% CI, 1.06-3.24; P = .031), depression (OR 1.75; 95% CI, 1.28-2.40; P = .001), and morbid obesity (OR 1.49; 95% CI, 1.04-2.13; P = .031). Estimated 2-year mortality was 61.5%, 64.2%, and 67.6% in patients with no/minimal, moderate, and severe difficulty, respectively. The adjusted hazard ratios (95% CI) for death were 1.08 (0.90-1.28) and 1.17 (0.95-1.43) for moderate and severe difficulty, respectively, vs no/minimal difficulty (P = .33). There were no statistically significant associations of difficulty with activities of daily living and hospitalization risks.ConclusionsMost patients with advanced heart failure have difficulty completing activities of daily living and are at high risk of mortality regardless of impairment in activities of daily living.     

Does Anatomic Versus Nonanatomic Resection Affect Recurrence and Survival in Patients Undergoing Surgery for Colorectal Liver Metastasis?

Anatomic resection of colorectal liver metastases may offer a survival advantage because (1) it removes the hepatic functional unit as a whole and (2) nonanatomic resection has been reported to have a higher incidence of positive margins. A retrospective review was performed of patients undergoing hepatic resection for colorectal liver metastases. 183 patients met inclusion criteria of undergoing either anatomic or nonanatomic resection with the aim of removing all gross disease. Mean age was 61 years (range 31–90 years), 57% were male. 89 patients (49%) underwent nonanatomic resection, the remaining 94 (51%) had anatomic resection. Average duration of inflow occlusion was 10 min. Average length of stay was 7.4 days. There were three deaths, yielding a 1.6% 30-day mortality rate. There was no difference in the incidence of positive margins between types of resection. Recurrence was 27%, 55%, and 59% at 1, 3, and 5 years respectively. Overall survival was 89%, 67%, and 55% at 1, 3, and 5 years, respectively. Type of resection was not associated with significant differences in recurrence or survival even when adjusted for differences in preoperative risk. We conclude that hepatic resection for colorectal metastases can be performed safely and offers select patients with stage IV disease prolonged survival. Resection type should be based on the number and location of tumors, rather than on segmental anatomy. An emphasis on the preservation of hepatic parenchyma may be of increasing importance in the setting of chemotherapy-associated steatohepatitis, and the growing number of patients undergoing repeated metastasectomy.     

Extracorporeal treatments for isoniazid poisoning: Systematic review and recommendations from the EXTRIP workgroup

Isoniazid toxicity from self-poisoning or dosing errors remains common in regions of the world where tuberculosis is prevalent. Although the treatment of isoniazid poisoning is centered on supportive care and pyridoxine administration, extracorporeal treatments (ECTRs), such as hemodialysis, have been advocated to enhance elimination of isoniazid. No systematic reviews or evidence-based recommendations currently exist on the benefit of ECTRs for isoniazid poisoning. The Extracorporeal Treatments in Poisoning (EXTRIP) workgroup systematically collected and rated the available evidence on the effect of and indications for ECTRs in cases of isoniazid poisoning. We conducted a systematic review of the literature, screened studies, extracted data on study characteristics, outcomes, and measurement characteristics, summarized findings, and formulated recommendations following published EXTRIP methods. Forty-three studies (two animal studies, 34 patient reports or patient series, and seven pharmacokinetic studies) met inclusion criteria. Toxicokinetic or pharmacokinetic analysis was available for 60 patients, most treated with hemodialysis (n = 38). The workgroup assessed isoniazid as “Moderately Dialyzable” by hemodialysis for patients with normal kidney function (quality of evidence = C) and “Dialyzable” by hemodialysis for patients with impaired kidney function (quality of evidence = A). Clinical data for ECTR in isoniazid poisoning were available for 40 patients. Mortality of the cohort was 12.5%. Historical controls who received modern standard care including appropriately dosed pyridoxine generally had excellent outcomes. No benefit could be extrapolated from ECTR, although there was evidence of added costs and harms related to the double lumen catheter insertion, the extracorporeal procedure itself, and the extracorporeal removal of pyridoxine. The EXTRIP workgroup suggests against performing ECTR in addition to standard care (weak recommendation, very low quality of evidence) in patients with isoniazid poisoning. If standard dose pyridoxine cannot be administered, we suggest performing ECTR only in patients with seizures refractory to GABA_A receptor agonists (weak recommendation, very low quality of evidence).     

Gastrointestinal infection in the immunocompromised (AIDS) patient

In the past two decades acquired immunodeficiency syndrome (AIDS) has become one of the most devastating illnesses in human history. As the epidemic continues to spread increasingly, AIDS patients are no longer confined to a few specialized AIDS hospitals and are now seen in general hospitals and clinics everywhere. Radiologists need to recognize the appearances, to understand how—safely—to care for patients with this disease, and to know enough about the illness to be able to counsel their patients. This article presents a review of current knowledge about the wide range of gastrointestinal hepatic, splenic, biliary, and retroperitoneal manifestations in AIDS, and how the role of modern medical imaging techniques and diagnosis and treatment can be applied. The imaging aspects (conventional double-contrast gastrointestinal studies, ultrasound, CT, and MR) of the diseases of the luminal gastrointestinal tract, liver, spleen, biliary tract, and retroperitoneum will be systematically discussed. Candidiasis, herpes, cytomegalovirus, cryptosporidiosis, histoplasmosis, isosporiasis, salmonellosis, toxoplasmosis, unusual mycobacteria, and viral infections account for the majority of non-neoplastic disorders.     

Erratum to: Rapid chemokinetic movement and the invasive potential of lung cancer cells; a functional molecular study

This is a correction of an earlier published article.     

Globoid cell leukodystrophy (Krabbe disease): Normal umbilical cord blood galactocerebrosidase activity and polymorphic mutations

Summary Globoid cell leukodystrophy is an inherited metabolic disorder of the central nervous system caused by deficiency of the lysosomal enzyme galactocerebrosidase. Haematopoietic stem cell transplantation is the only available effective treatment. The engraftment from normal donors provides competent cells able to correct the metabolic defect. Umbilical cord blood cells have proved to significantly decrease complications and improve engraftment rate compared to adult marrow cells in haematopoietic stem cell transplantation. Umbilical cord blood cells must be of sufficient activity to provide central nervous system recovery after engraftment is obtained. Galactocerebrosidase activity is known to be affected by two polymorphic alleles found at nucleotides 502 and 1637 of the cDNA for this gene. This enzyme activity and the polymorphic alleles noted above were analysed in 83 random samples of umbilical cord blood. The activity, assayed with the fluorogenic substrate 6-hexadecanoylamino-4-methylumbelliferyl-β-galactopyranoside, in those with neither polymorphic allele was 4.6 ± 1.7 units (nmol/h per mg protein). This optimal choice of cord blood was found in only 24% of specimens. Homozygotes for 1637T > C with activity of only 1.5 ± 0.4 units represented 16% of the samples. Those heterozygous for 1637T > C with slightly better activity (2.3 ± 0.7 units) represented 52% of the samples. Choice of umbilical cord blood for haematopoietic stem cell transplantation, therefore, requires consideration not only of cell quantity and HLA compatibility but also selection for normal alleles to obtain maximal enzymatic activity for central nervous system correction.