Systematic review: cystic fibrosis in the SARS-CoV-2/COVID-19 pandemic.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the development of life-threatening COVID-19 are believed to disproportionately affect certain at-risk populations. However, it is not clear whether individuals with cystic fibrosis (CF) are at a higher risk of COVID-19 or its adverse consequences. Recurrent respiratory viral infections are often associated with perturbation and pulmonary exacerbations of CF as evidenced by the significant morbidity observed in CF individuals during the 2009 H1N1 pandemic. The primary goal of this review was to systematically survey published accounts of COVID-19 in CF and determine if individuals with CF are disproportionally affected by SARS-CoV-2 and development of COVID-19. METHODS: We conducted a systematic literature search using EMBASE and Medline between April 28 and December 10, 2020. Six evaluable studies reporting on a total of 339 individuals with CF who developed COVID-19 were included in this study. RESULTS: We found that although individuals with CF generally experience acute exacerbations of lung disease from infectious agents, COVID-19 incidence estimates in CF appear to be lower than in the general population. However, there are reports of subsets of CF, such as those who had organ transplants, that may experience a more severe COVID-19 course. Potential protective mechanisms in the CF population include pre-pandemic social isolation practices, infection prevention and control knowledge, altered expression of angiotensin-converting enzyme, and the use of certain medications. CONCLUSIONS: Although individuals with CF are at risk of acute exacerbations often precipitated by respiratory tract viral infections, published evidence to date indicated that individuals with CF do not experience higher risks of contracting SARS-CoV-2 infection. However, there is evidence that some subsets within the CF population, including those post-transplantation, may experience a more severe clinical course. As SARS-CoV-2 variants are identified and the pandemic goes through additional waves of disease outbreaks, ongoing monitoring of the risk of COVID-19 in individuals with CF is required.

Do prenatal exposures pose a real threat to ovarian function? Bisphenol A as a case study.

Fetal development represents a time of potential vulnerability due to rapid cell division, organ development and limited fetal kidney/liver activity for detoxification and metabolism of exposures. Health effects of prenatal toxicant exposure have previously been described, but there is little cohesive evidence surrounding effects on ovarian function. Using bisphenol A (BPA) as a case study, we seek to examine whether a prominent prenatal environmental exposure can pose a real threat to human ovarian function. To do so, we broadly review human oogenesis and menstrual cycle biology. We then present available literature addressing prenatal bisphenol A and diverse outcomes at the level of the ovary. We highlight relevant human cohorts and mammalian models to review the existing data on prenatal exposures and ovarian disruption. Doing so suggests that while current exposures to BPA have not shown marked or consistent results, there is data sufficient to raise concerns regarding ovarian function. Challenges in the examination of this question suggest the need for additional models and pathways by which to expand these examinations in humans.

Lorcaserin treatment decreases body weight and reduces cardiometabolic risk factors in obese adults: A six-month, randomized, placebo-controlled, double-blind clinical trial.

Lorcaserin is a serotonin 2c receptor agonist that promotes weight loss while contributing to the prevention and improvement of type 2 diabetes and improvement of atherogenic lipid profiles, without higher rates of major cardiovascular events. The full spectrum of possible lorcaserin-induced improvements in cardiometabolic health remains to be clarified. Thus, we investigated the way in which lorcaserin treatment may alter cardiovascular disease risk, either independently or through changes in body weight. We measured, for the first time, lipid particle quantification, lipid peroxidation, appetite-regulating hormones and mRNA expression of the 5-hydroxytryptamine 2c receptor (5-HT2c receptor). A total of 48 obese participants were enrolled in this six-month, randomized (1:1), placebo-controlled, double-blinded clinical trial. Lorcaserin treatment reduced fat mass (P < 0.001), the fatty liver index (P < 0.0001) and energy intake (P < 0.03) without affecting energy expenditure or lean mass. Total low-density lipoprotein (LDL) (P < 0.04) and small LDL particles (P < 0.03) decreased, while total high-density lipoprotein (HDL) P < 0.02) increased and heart rate significantly decreased with lorcaserin treatment. No mRNA expression of the 5-HT2c receptor was observed in peripheral organs. These data suggest that lorcaserin treatment for six months improves cardiometabolic health in obese individuals, acting mainly through the brain.

Longer-term liraglutide administration at the highest dose approved for obesity increases reward-related orbitofrontal cortex activation in response to food cues: Implications for plateauing weight loss in response to anti-obesity therapies.

AIMS: GLP-1 analogs have recently risen to the forefront as effective medications for lowering weight through actions in the central nervous system (CNS). However, their actions in the CNS have not yet been studied in the human brain after longer-term administration at the highest dose approved for obesity (liraglutide 3.0 mg). MATERIALS AND METHODS: A total of 20 participants with obesity were treated with placebo and liraglutide (3.0 mg) in the context of a randomized, placebo-controlled, double-blind, cross-over trial after 5 weeks of dose escalation. Neurocognitive and neuroimaging (fMRI) responses to food cues were examined at the clinical research center of Beth Israel Deaconess Medical Center. RESULTS: While using liraglutide, patients lost more weight (placebo-subtracted -2.7%; P < .001), had decreased fasting glucose (P < .001) and showed improved cholesterol levels. In an uncontrolled analysis, brain activation in response to food images was not altered by liraglutide vs placebo. When controlled for BMI/weight, liraglutide increased activation of the right orbitofrontal cortex (OFC) in response to food cues (P < .016, corrected for multiple comparisons). CONCLUSIONS: In contrast to prior studies, we demonstrate for the first time that liraglutide treatment, administered over a longer period at the highest doses approved for obesity, does not alter brain activation in response to food cues. A counter-regulatory increase in reward-related OFC activation in response to food cues can be observed when neuroimaging data are controlled for BMI changes, indicating changes in CNS that could lead to later plateaus of weight loss. These data point to a promising focus for additional interventions which, by contributing to the CNS reward system, could provide tangible benefits in reversing the plateauing phenomenon and promoting further weight loss.

Mimics of cancer in pregnancy.

Pregnancy is a remarkable time of pronounced growth and development of the fetus. Benign pathologies outside of the uterus, including those containing hormonally responsive tissue which undergo physiologic changes and other incidentally identified lesions, may mimic malignancy on clinical evaluation and imaging. A detailed history and physical exam, ultrasound and non-contrast magnetic resonance imaging features and comparison with prior imaging if available may help to narrow the list of potential differential diagnoses. Follow-up imaging in the postpartum period is often vital to confirm benignity and, in some cases, sampling to confirm the diagnosis is necessary. This review will cover the clinical, pathological and multimodality imaging features of numerous potential mimickers of cancer in the setting of pregnancy organized by organ systems. The goal is to better equip abdominal radiologists to accurately identify benign disease and help guide further imaging or follow-up recommendations to avoid unnecessarily aggressive intervention and improve patient care.

Cytokine autoantibodies in SARS-CoV-2 prepandemic and intrapandemic samples from an SLE cohort.

Cytokine autoantibodies, particularly those directed to type I interferon (T1IFN), have been reported to portend an increased risk of severe COVID-19. Since SLE is one of the conditions historically associated with T1IFN autoantibodies, we sought to determine the prevalence of cytokine autoantibodies in our local cohort of 173 patients with SLE prepandemic and intrapandemic, of which nine had confirmed exposure to SARS-CoV-2. Autoantibodies to 16 different cytokines, including T1IFN, were measured by an addressable laser bead immunoassay. None of the 9 patients with confirmed exposure to SARS-CoV-2 had autoantibodies to T1IFN and none had severe COVID-19 symptoms, necessitating hospitalisation. Hence, we could not confirm that TIIFN autoantibodies increase the risk for severe COVID-19. In addition, the cytokine autoantibody pattern did not differ between those with and without evidence of SARS-CoV-2 exposure.

The effect of excess body fat on female and male reproduction.

The dramatic increase in the prevalence of obesity coincides with a decline in reproductive health indices in both sexes. Energy excess mediates changes to the regulatory mechanisms of the reproductive system. Obese individuals exhibit increased estrogen concentrations, due to the overexpression of aromatase in the adipose tissue; via a negative feedback loop, men present with symptoms of hypogonadotropic hypogonadism. These hormonal changes, along with increased oxidative stress, lipotoxicity and disturbances in the concentrations of adipokines, directly affect the gonads, peripheral reproductive organs and the embryo. Clinical evidence is somewhat contradicting, with only some studies advocating worse semen parameters, increased incidence of erectile dysfunction, increased doses of ovulation induction medications, and worse live birth rates in assisted reproductive technology (ART) cycles in obese individuals compared with those of normal weight. Similar conclusions are drawn about patients with insulin resistance syndromes, namely polycystic ovary syndrome (PCOS). As far as treatment options are concerned, lifestyle changes, medical therapy and bariatric surgery may improve the reproductive outcome, although the evidence remains inconclusive. In this review, we summarize the evidence on the association of obesity and reproductive health on both the molecular and the clinical level, and the effect of weight-loss interventions on reproductive potential.

Menstrual patterns and self-reported hirsutism as assessed via the modified Ferriman-Gallwey scale: A cross-sectional study.

OBJECTIVE: Hirsutism, the presence of excess terminal hair in a male pattern, is a clinical marker of androgen excess in women. We used cross-sectional data from a North American preconception cohort study to evaluate the association between menstrual cycle characteristics and hirsutism. STUDY DESIGN: Women aged 21-45 years were recruited to a North American cohort of pregnancy planners. On the baseline questionnaire, participants self-reported menstrual characteristics, which included menstrual regularity, cycle length, bleed length, and bleed heaviness. Participants provided a self-rating of hirsutism in nine distinct body areas using pictograms representing the modified Ferriman-Gallwey (mFG) score. Using their ratings, we calculated total mFG scores and defined hirsutism as mFG scores ≥8. We used log-binomial regression models to estimate prevalence ratios (PRs) for the association between menstrual characteristics and hirsutism assessed at baseline. RESULTS: We included 5,542 women in the analytic cohort. Mean mFG score was 4.7, with 21.7 % reporting mFG scores ≥8. Compared with women with regular menstrual cycles, irregular cycles were positively associated with mFG ≥8 (PR 1.73, 95 % CI 1.56-1.91). Bleed lengths of ≥7 days compared with <3 days also showed a positive association with mFG score ≥8 (PR 1.59, 95 % CI 1.16-2.19), as did heavy bleeds (PR 1.42, 95 % CI 1.21-1.67) compared with moderate bleeds. Findings remained consistent when restricted to women without a prior diagnosis of polycystic ovary syndrome. CONCLUSIONS: In a population-based cohort of North American women, menstrual irregularity, increased cycle and bleeds lengths, and heavier menstrual bleeds were associated with self-reported hirsutism.

RAPIDLY PROGRESSIVE AND SEVERE HIRSUTISM FROM HYPERREACTIO LUTEINALIS WITHIN A BACKGROUND OF POLYCYSTIC OVARY SYNDROME.

OBJECTIVE: Gestational trophoblastic disease and hyperreactio luteinalis (HL) are rare, but important, etiologies of hyperandrogenism that need to be further studied. METHODS: We present a case of rapidly progressing hirsutism and marked biochemical androgen excess in the context of pregnancy. RESULTS: A 26-year-old woman with a past medical history of obesity, prediabetes, and polycystic ovary syndrome presented with worsening hirsutism and markedly elevated testosterone levels. She was subsequently found to be pregnant, with extremely elevated levels of serum ß-human chorionic gonadotropin. Subsequent work-up led to the identification of molar pregnancy and bilaterally enlarged ovaries, suggestive of HL. Following surgical intervention and therapy with methotrexate for invasive mole, she experienced improvement in both biochemical and clinical androgen excess features. CONCLUSION: With the prevalence of polycystic ovary syndrome, many women present to medical providers with hirsutism or other findings of hyperandrogenism. However, rapid progression of existing hirsutism or severe hirsutism should prompt more extensive evaluations to rule out rare etiologies. One such etiology found in pregnancy is HL, in which high levels of ß-human chorionic gonadotropin can stimulate production of benign theca lutein cysts, leading to marked hyperandrogenism and virilizing symptoms.

Adipose tissue and reproductive health.

The understanding of adipose tissue role has evolved from that of a depot energy storage organ to a dynamic endocrine organ. While genetics, sexual phenotype and sex steroids can impact the mass and distribution of adipose tissue, there is a counter-influence of white adipocytes on reproduction. This primarily occurs via the secretion of adipokines, the most studied of which- leptin and adiponectin- are highlighted in this article. Leptin, the "satiety hormone" primarily acts on the hypothalamus via pro-opiomelanocortin (POMC), neuropeptide Y (NPY), and agouti-related peptide (AgRP) neurons to translate acute changes in nutrition and energy expenditure, as well as chronic adipose accumulation into changes in appetite and potentially mediate insulin resistance via shared pathway and notably impacting reproductive health via influence on GnRH secreting neurons. Meanwhile, adiponectin is notable for its action in mediating insulin sensitivity, with receptors found at every level of the reproductive axis. Both have been examined in the context of physiologic and pathologic reproductive conditions. Leptin has been shown to influence puberty, pregnancy, hypothalamic amenorrhea, and lipodystrophy, and with a potential therapeutic role for both metabolic and reproductive health. Adiponectin mediates the relative state of insulin resistance in pregnancy, and has been implicated in conditions such as polycystic ovary syndrome and reproductive malignancies. There are numerous other adipokines, including resistin, visfatin, chemerin and retinol binding protein-4, which may also play roles in reproductive health and disease states. The continued examination of these and other adipokines in both normal reproduction and reproductive pathologies represents an important avenue for continued study. Here, we seek to provide a broad, yet comprehensive overview of many facets of these relationships and highlight areas of consideration for clinicians and future study.

Lorcaserin Administration Decreases Activation of Brain Centers in Response to Food Cues and These Emotion- and Salience-Related Changes Correlate With Weight Loss Effects: A 4-Week-Long Randomized, Placebo-Controlled, Double-Blind Clinical Trial.

Lorcaserin is a serotonin 5-hydroxytryptamine 2c receptor agonist effective in treating obesity. Studies in rodents have shown that lorcaserin acts in the brain to exert its weight-reducing effects, but this has not yet been studied in humans. We performed a randomized, placebo-controlled, double-blind trial with 48 obese participants and used functional MRI to study the effects of lorcaserin on the brain. Subjects taking lorcaserin had decreased brain activations in the attention-related parietal and visual cortices in response to highly palatable food cues at 1 week in the fasting state and in the parietal cortex in response to any food cues at 4 weeks in the fed state. Decreases in emotion- and salience-related limbic activity, including the insula and amygdala, were attenuated at 4 weeks. Decreases in caloric intake, weight, and BMI correlated with activations in the amygdala, parietal, and visual cortices at baseline. These data suggest that lorcaserin exerts its weight-reducing effects by decreasing attention-related brain activations to food cues (parietal and visual cortices) and emotional and limbic activity (insula, amygdala). Results indicating that baseline activation of the amygdala relates to increased efficacy suggest that lorcaserin would be of particular benefit to emotional eaters.

Howell-Jolly bodies on peripheral smear leading to the diagnosis of congenital hyposplenism in a patient with septic shock.

We present a case of isolated congenital hyposplenism that was discovered after the peripheral smear revealed Howell-Jolly bodies. This case serves as the basis for a review of hyposplenism for the general practitioner.

Bone marrow infiltration as the initial presentation of gastric signet ring cell adenocarcinoma.

This case report describes a 52-year-old African American man who initially presented with worsening back pain. The patient was found to have lytic lucencies in the T5 and T9 vertebral bodies and a subsequent bone marrow biopsy revealed an extensive infiltrate of signet ring cells. These findings prompted a workup for a gastrointestinal malignancy, and upper endoscopy revealed a mass in the gastric pylorus. A biopsy of this mass was positive for signet ring cell adenocarcinoma. This case is significant for two reasons. First, it highlights the importance of a broad differential diagnosis when approaching a patient with lytic bone lesions. Second, bone marrow involvement is more common in patients with diffuse type gastric cancer and occurs in particularly young patients. The increasing incidence of diffuse type gastric adenocarcinoma means bone marrow metastases will likely play a greater role in the presentation and management of gastric cancer.