Evolution Under Thermal Stress Affects Escherichia coli's Resistance to Antibiotics.

Exposure to both antibiotics and temperature changes can induce similar physiological responses in bacteria. Thus, changes in growth temperature may affect antibiotic resistance. Previous studies have found that evolution under antibiotic stress causes shifts in the optimal growth temperature of bacteria. However, little is known about how evolution under thermal stress affects antibiotic resistance. We examined 100+ heat-evolved strains of Escherichia coli that evolved under thermal stress. We asked whether evolution under thermal stress affects optimal growth temperature, if there are any correlations between evolving in high temperatures and antibiotic resistance, and if these strains' antibiotic efficacy changes depending on the local environment's temperature. We found that: (1) surprisingly, most of the heat-evolved strains displayed a decrease in optimal growth temperature and overall growth relative to the ancestor strain, (2) there were complex patterns of changes in antibiotic resistance when comparing the heat-evolved strains to the ancestor strain, and (3) there were few significant correlations among changes in antibiotic resistance, optimal growth temperature, and overall growth.

Role of body mass index in outcomes of patients hospitalized with COVID-19 illness.

Background: Since the start of coronavirus disease 2019 (COVID-19) pandemic, several studies have linked obesity with severity of illness as well as mortality in patients with COVID-19. Outcomes of patients with overweight or obesity, who develop critical illness, have been studied extensively over the past decade where the studies have shown conflicting results. In this study, we aimed to assess the association between the body mass index (BMI) classes and outcomes among hospitalized patients with COVID-19. Methods: This was a retrospective chart review of all adults admitted to our hospital with COVID-19 illness between 1 March 2020 and 30 June 2020. Patients were divided into four groups based on their BMI range as follows: patients with underweight (BMI < 18.5 kg/m2), patients with normal weight (BMI 18.5-24.9 kg/m2), patients with overweight (BMI 25-29.9 kg/m2), and patients with obesity (BMI ≥ 30 kg/m2). Results: 1274 patients were admitted during the study period. There were 24 (1.9%) patients with underweight, 268 (21%) patients with normal weight, 445 (34.9%) patients with overweight, and 537 (42.2%) patients with obesity. Patients with obesity were younger (p < 0.001) and there were more females among patients with underweight and patients with obesity (54% and 48% respectively, p < 0.001). There were no differences in subgroup with regards to presence of hypertension, diabetes mellitus, coronary artery disease, congestive heart failure, and dyslipidemia. In a multivariate logistic regression model, patients with overweight and patients with obesity had higher odds of requiring mechanical ventilation. BMI class was not associated with difference in survival time in a multivariate analysis. Conclusions: In our large single-center study of hospitalized patients with COVID-19, patients with overweight and obesity had higher need for mechanical ventilation but had similar mortality when compared to patients with normal weight and underweight.

Hypercalcemia and Renal Mass: A Diagnostically Challenging Case.

Hypercalcemia of malignancy frequently occurs in patients with solid tumors as a paraneoplastic syndrome known as humoral hypercalcemia of malignancy (HHM), caused by the secretion of parathyroid hormone-related peptide (PTHrP). On the other hand, 1,25-dihydroxyvitamin D [1,25(OH)2D]-mediated hypercalcemia is a less common cause of hypercalcemia of malignancy and is mostly observed in lymphoma patients. Here, we report an interesting case of a 77-year-old male nursing home resident with suspected renal cell carcinoma (RCC) presenting with severe hypercalcemia (18.7 mg/dL), which was initially presumed to be HHM. However, workup revealed nonsuppressed parathyroid hormone, low PTHrP, and elevated 25-hydroxyvitamin D and 1,25(OH)2D levels. Steroids were initiated due to an inadequate response to bisphosphonate therapy and elevated vitamin D metabolites, resulting in further reduction in serum calcium levels. This case highlights the need to consider multiple concurrent etiologies in the differential diagnosis of severe hypercalcemia, including the possible role of calcitriol-mediated hypercalcemia in RCC.

Prevalence of advanced liver fibrosis and steatosis in type-2 diabetics with normal transaminases: A prospective cohort study.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) and type-2 diabetes mellitus (T2DM) have an intricate bidirectional relationship. Individuals with T2DM, not only have a higher prevalence of non-alcoholic steatosis, but also carry a higher risk of progression to nonalcoholic steatohepatitis. Experts still differ in their recommendations of screening for NAFLD among patients with T2DM. AIM: To study the prevalence of NAFLD and advanced fibrosis among our patient population with T2DM. METHODS: During the study period (November 2018 to January 2020), 59 adult patients with T2DM and 26 non-diabetic control group individuals were recruited prospectively. Patients with known significant liver disease and alcohol use were excluded. Demographic data and lab parameters were recorded. Liver elastography was performed in all patients. RESULTS: In the study group comprised of patients with T2DM and normal alanine aminotransferase levels (mean 17.8 ± 7 U/L), 81% had hepatic steatosis as diagnosed by elastography. Advanced hepatic fibrosis (stage F3 or F4) was present in 12% of patients with T2DM as compared to none in the control group. Patients with T2DM also had higher number of individuals with grade 3 steatosis [45.8% vs 11.5%, (P < 0.00001) and metabolic syndrome (84.7% vs 11.5%, P < 0.00001)]. CONCLUSION: A significant number of patients with T2DM, despite having normal transaminase levels, have NAFLD, grade 3 steatosis and advanced hepatic fibrosis as measured by liver elastography.

Psychological aspects of gestational cancer: A systematic review.

OBJECTIVE: Gestational cancer is defined as any type of cancer diagnosed during pregnancy or within 12 months of delivery. To date, existing studies on the psychological aspects of this type of cancer have not been evaluated for methodological quality. The aim of this systematic review was to identify the psychological aspects of gestational cancer. METHODS: Five journal databases were searched to identify peer-reviewed articles reporting upon the psychological aspects of women with gestational cancer. Studies published from journal inception to December 2019 were included, and Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed. The Mixed-Method Appraisal Bias Tool was used, to assess the methodological quality of the studies. A narrative description was developed for the psychological outcomes reported in quantitative studies. Qualitative data was synthesized using thematic analysis. RESULTS: Five papers were eligible for inclusion (two qualitative and three quantitative studies). Factors that contributed to women's psychological distress during gestational cancer included disease characteristics, sociodemographic factors, the baby's health, pregnancy-related factors and cognitive emotion regulation. Four main themes emerged from the qualitative studies; concerns about the baby's health, lost opportunities, "not fitting in," and healthcare decision-making. CONCLUSIONS: These findings suggest that (a) women with gestational cancer experience psychological distress that is associated with concerns about their babies' health, and (b) their healthcare experiences are affected by communication within multidisciplinary care teams.

Perioperative Management of Patients with Diabetes.

Hyperglycemia has long been recognized to have detrimental effects on postoperative outcomes in patients undergoing surgery. The manifestations of uncontrolled diabetes are manifold and can include risk of hyperglycemic crises, postoperative infection, poor wound healing, and increased mortality. There is substantial literature supporting the role of diligent glucose control in the prevention of adverse surgical outcomes, but considerable debate remains as to the optimal glucose targets. Hence, most organizations advocate the avoidance of hypoglycemia while striving for adequate glucose control in the perioperative period. These objectives can be accomplished with careful preoperative evaluation, clear patient instructions the day of surgery, frequent blood glucose monitoring during the perioperative period, and use of effective strategies for insulin initiation and titration. This article highlights the major issues concerning patients with diabetes undergoing surgery and reviews the management recommendations put forth by general consensus guidelines and expert opinion.

Effect of Recombinant Human Growth Hormone and Rosiglitazone for HIV-Associated Abdominal Fat Accumulation on Adiponectin and other Markers of Inflammation.

BACKGROUND/OBJECTIVE: In a previous report of HIV-infected patients with fat redistribution, we found that recombinant human growth hormone (rhGH) therapy reduced visceral adipose tissue (VAT) but increased insulin resistance, and that the addition of rosiglitazone reversed the negative effects of rhGH on insulin sensitivity. In this study, we sought to determine the effects of rhGH and rosiglitazone therapy on an array of inflammatory and fibrinolytic markers. METHODS: 72 patients with HIV-associated abdominal obesity and insulin resistance were randomized to treatment with rhGH, rosiglitazone, the combination of rhGH and rosiglitazone, or placebo for 12 weeks. Subjects with plasma and serum samples available at weeks 0 (n=63) and 12 (n=46-48) were assessed for adiponectin, C-reactive protein, homocysteine, interleukin-1, interleukin-6, tumor necrosis factor alpha, interferon gamma, fibrinogen, plasminogen activator inhibitor-1 antigen, and tissue plasminogen activator antigen. RESULTS: Treatment with both rosiglitazone alone and the combination of rosiglitazone and rhGH for 12 weeks resulted in significant increases in adiponectin levels from baseline. Adiponectin levels did not change significantly in the rhGH arm alone . There were no significant changes in the other biomarkers among the different treatment groups. DISCUSSION: In this study of HIV-infected patients with altered fat distribution, treatment with rosiglitazone had beneficial effects on adiponectin concentrations, an effect that was also seen with a combination of rosiglitazone and rhGH. RhGH administration alone, however, did not demonstrate any significant impact on adiponectin levels despite reductions in VAT.

A rare case of insulinoma presenting with postprandial hypoglycemia.

BACKGROUND: Although fasting hypoglycemia has historically been considered the hallmark of insulinoma, postprandial hypoglycemia has also been occasionally reported as the predominant feature. We report a rare case of an insulinoma diagnosed in an individual presenting exclusively with postprandial hypoglycemia without fasting hypoglycemia. CASE REPORT: A 47-year-old woman with medical history of migraine, depression, hypercholesterolemia, iron deficiency anemia, and peptic ulcer disease presented with complaints of frequent episodes of dizziness, blurring of vision, and anxiety over the past 4 months. These episodes usually occurred 1-2 hours after eating and resolved with ingestion of sugary foods. Home glucometer readings during typical symptoms were 47-64 mg/dL. Physical exam revealed a healthy-appearing middle-aged female with BMI of 28. Laboratory data after an overnight fast showed serum blood glucose 77 mg/dL and AM cortisol 9.6 (5-25 µg/dl). Hemoglobin A1C, thyroid function tests, IGF-1, liver function tests, and kidney function were in normal range. She was instructed to bring a typical meal to the clinic for monitoring of postprandial glucose levels. Three hours after ingestion of the meal, she developed typical adrenergic symptoms during which laboratory analysis revealed a serum glucose level of 44 mg/dL, C-peptide of 2.9 (0.8-3.1 ng/ml), insulin level of 32 (0-17 µIU/lt), negative sulfonylurea screen, and insulin antibodies. She was treated with 15 grams of oral glucose, which alleviated her symptoms. Medical therapy with acarbose was attempted, but did not lead to significant reduction in hypoglycemic events. CT abdomen/pelvis confirmed the presence of a tumor in the tail of the pancreas. The patient subsequently underwent partial pancreatectomy, splenectomy, and lymph node resection, with resolution of symptoms. Histopathological analysis confirmed insulinoma. CONCLUSIONS: We present a rare case of an insulinoma in the setting of verified postprandial hypoglycemia with elevated insulin and C-peptide levels. Although insulinomas typically present with fasting hypoglycemia, it is important to consider insulinoma in the differential diagnosis of patients presenting exclusively with postprandial hypoglycemia.

Skeletal-related events due to bone metastases from differentiated thyroid cancer.

BACKGROUND: In oncology, the clinical impact of metastatic bone disease is conveyed via a composite end point termed skeletal-related events (SRE), which encompasses spinal cord compression, pathological fracture, a need for external beam radiation or surgery to bone, and hypercalcemia of malignancy. An appreciation for the high incidence of SRE in other advanced cancers involving the bone has led to the approval of potent antiresorptive agents because they delay the time to the first SRE and decrease the incidence of SRE. The risk and rate of SRE after diagnosis of bone metastasis have not been described in thyroid cancer; antiresorptive agents are not routinely used. METHODS: This was a retrospective review of 245 differentiated thyroid cancer patients with bone metastases identified as part of routine clinical care at Memorial Sloan-Kettering Cancer Center between 1960 and 2011. The occurrence of SRE was recorded from the initial diagnosis of bone metastasis until final follow-up or death. RESULTS: Seventy-eight percent of patients (192 of 245) either presented with or developed at least one SRE after the diagnosis of metastatic bone disease. The median time from identification of bone metastasis to first SRE was 5 months (excluding the 97 patients in whom first SRE occurred at the time of the bone metastasis diagnosis). Of the patients who sustained an initial SRE, 65% (120 of 192) went on to sustain a second SRE at a median of 10.7 months after the first event. SRE were frequently multiple; 39% (74 of 192) sustained three or more discrete SRE. CONCLUSION: Thyroid cancer bone metastases identified as part of routine clinical follow-up frequently cause significant and recurrent morbidity. The incidence of SRE and median time to first SRE in metastatic thyroid cancer to bone are similar to those reported in other solid tumors. Prospective clinical trials to assess the efficacy of antiresorptive agents in this population are needed.

Diabetes-specific quality of life after a low-carbohydrate and low-fat dietary intervention.

PURPOSE: The purpose of the study was to examine the impact of a 12-month weight loss intervention with either a low-carbohydrate or a low-fat diet on quality of life (QOL) among obese patients with type 2 diabetes. METHODS: Participants were enrolled in a randomized trial comparing a low-carbohydrate to a low-fat diet in type 2 diabetes. QOL was assessed with the Diabetes-39 questionnaire, which measures QOL within 5 distinct scales: anxiety and worry, diabetes control, energy and mobility, social burden, and sexual functioning. Repeated measures ANOVA compared change in QOL scales at baseline and 6 and 12 months. RESULTS: Forty-six participants completed all measures. Following 12 months, there was a significant reduction in the scores related to sexual function and energy and mobility, suggesting improvement in QOL related to these domains. These changes were not significantly different between dietary arms. Changes in weight, A1C, and dietary composition were not significantly correlated with changes in QOL. CONCLUSIONS: Participants with diabetes have various options for weight loss. Dietary interventions with either low-carbohydrate or low-fat diets may lead to some improvements in QOL in patients with type 2 diabetes.

Pathogenesis and treatment of HIV lipohypertrophy.

PURPOSE OF REVIEW: This review addresses our current understanding of the pathogenesis of HIV-associated lipohypertrophy and describes an evidence-based approach to treatment. RECENT FINDINGS: Although the pathogenesis of HIV-associated lipohypertrophy remains elusive, recent clinical and laboratory investigations in fatty acid metabolism and growth hormone dynamics have furthered our understanding of the condition. These findings have also paved the way for new therapeutic interventions, of which tesamorelin, an analog of growth hormone-releasing hormone (GHRH), has gained recognition as a promising treatment strategy against visceral fat accumulation. Recent randomized placebo-controlled trials of tesamorelin demonstrated significant reductions in visceral adipose tissue, improvement in lipid parameters, and minimal adverse effects on glucose tolerance. Optimal therapeutic dosing and treatment duration, though, are not yet known. Whether treatment with GHRH-analogs will translate into improved long-term metabolic and cardiovascular outcomes also remains to be seen. SUMMARY: Although the pathogenesis of HIV lipohypertrophy remains unclear, several theories and observations have led to the development of treatment strategies to counter fat accumulation and its accompanying metabolic complications. Based on clinical trials, analogs of the growth hormone (GH)/GHRH axis appear to be most effective in reducing visceral adipose tissue.