Investigations and management of chronic cough: a 2020 update from the European Respiratory Society Chronic Cough Task Force.

Chronic cough affects approximately 10% of the general population, is highest amongst people aged 50 to 60 years, and is twice as common in women than men. It is described to last 8 weeks or longer in adults and does not respond well to treatment with over-the-counter medications and those targeting potential associated conditions. This is a debilitating condition with physical, social, and psychological consequences. The purpose of this review was to highlight the key messages on the management of chronic cough from the task force commissioned by the European Respiratory Society. The assessment of patients with chronic cough should include a thorough detailed history and examination to identify potential causes. The impact and severity can be assessed in a clinic using questionnaires. Potential causes of the condition vary and include, for example, angiotensin­converting enzyme inhibitors, smoking, asthma, nonasthmatic eosinophilic bronchitis, gastroesophageal reflux disease, and upper airways cough syndrome. In many patients, coughing is persistent despite optimum medical therapy of the underlying medical condition and is hence referred to as refractory chronic cough. In some cases, no cause can be found and the cough is classified as unexplained chronic cough. If treatment of any underlying disease is unsuccessful at controlling cough, then neuromodulatory treatment such as a low­dose opioid, gabapentin, pregabalin or speech and language therapy may be considered. There is no licensed treatment for chronic cough, but a new class of treatment targeting the purinergic P2X3 receptor is currently in phase 2 and 3 of development.

The MOV10 helicase inhibits LINE-1 mobility.

LINE-1 (long interspersed element 1) is an autonomous non-long terminal repeat retrotransposon. Its replication often causes mutation and rearrangement of host genomic DNA. Accordingly, host cells have evolved mechanisms to control LINE-1 mobility. Here, we report that a helicase named MOV10 effectively suppresses LINE-1 transposition. Mutating the helicase motifs impairs this function of MOV10, suggesting that MOV10 requires its helicase activity to suppress LINE-1 replication. Further studies show that MOV10 post-transcriptionally diminishes the level of LINE-1 RNA. The association of MOV10 with both LINE-1 RNA and ORF1 suggests that MOV10 interacts with LINE-1 RNP and consequently causes its RNA degradation. These data demonstrate collectively that MOV10 contributes to the cellular control of LINE-1 replication.

Restoration of glycemic control in patients with type 2 diabetes mellitus after bariatric surgery is associated with reduction in microparticles.

BACKGROUND: Microparticles bud from cellular elements during inflammation and are associated with the vascular dysfunction related to type 2 diabetes mellitus. Although weight loss is known to reduce inflammation, the metabolic effects of bariatric surgery on microparticle concentration and composition are not known. Our objectives were to determine the effect of bariatric surgery on the microparticle concentration and to correlate these changes with clinical parameters in a multispecialty group practice. METHODS: We studied 14 obese subjects with type 2 diabetes mellitus 2 weeks before and 1 and 12 months after bariatric surgery. Of the 14 patients, 9 underwent Roux-en-Y gastric bypass and 5 gastric restrictive surgery. RESULTS: At 1 month after surgery, the body mass index had decreased by ∼10%, glycemic control had improved dramatically (P < .01), and a >60% reduction in endothelial and platelet microparticles and C-reactive protein levels (P < .05) had occurred. The tissue factor microparticles had decreased by 40% (P = .1). At 12 months after surgery, the body mass index had decreased by ∼20%, glycemic control was maintained (P < .01), and a >50% reduction in monocyte microparticles compared with before surgery was found. The reduction in monocyte microparticles 1 month after surgery was strongly associated with the reduction in hemoglobin A1c (P < .05). The reduction in monocyte microparticles 12 months after surgery correlated strongly with the reduction in body mass index (P < .05). CONCLUSION: The reduction in microparticles after bariatric surgery in patients with type 2 diabetes mellitus reflects an attenuation of inflammation, and this mechanism might contribute to normalization of glycemic control.

Co-occurrence of papillary thyroid carcinoma and primary lymphoma of the thyroid in a patient with long-standing Hashimoto's thyroiditis.

BACKGROUND: Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer, whereas mucosa-associated lymphoid tissue (MALT) lymphoma of the thyroid gland is uncommon. Simultaneous occurrence of both disease entities is very rare. PATIENT FINDINGS: A 59-year-old man with known hypothyroidism from Hashimoto's thyroiditis (HT) was seen for thyroid nodules. A thyroid ultrasound revealed a heterogeneous thyroid gland with two hypoechoic nodules, one in the right aspect of the isthmus measuring 2.0 cm×3.2 cm×1.7 cm and another one in the left lobe measuring 1.4 cm×1.3 cm×1.2 cm. A fine-needle aspiration (FNA) of the right-sided nodule revealed atypical epithelial cells and atypical lymphoid cells in a background of lymphocytic thyroiditis; FNA of the left-sided nodule showed findings of PTC. A total thyroidectomy was performed. Lymph node dissection was not performed. Pathology showed extranodal marginal zone B-cell lymphoma of MALT type with extreme plasmacytic differentiation in the right nodule and PTC in the left nodule (pT1b Nx Mx). Postoperatively, he underwent radioactive iodine ablation treatment. There was only minimal neck uptake on the post-treatment scan. Further work-up did not show any evidence of extrathyroidal lymphoma. Seven years after the surgery, the patient had no evidence of recurrence of either malignancy. SUMMARY: PTC is the most prevalent thyroid cancer and has an excellent prognosis. Primary thyroid lymphoma is rare and accounts for <5% of all thyroid cancers. Among the primary thyroid lymphomas, MALT lymphoma tends to have a more indolent course and a better prognosis. PTC and MALT lymphoma have been associated with HT. FNA has been validated in several studies for the diagnosis of MALT lymphoma; however, distinguishing MALT lymphoma from HT remains a challenge due to their histological similarities. The treatment of MALT lymphoma remains controversial; however, surgery is generally accepted in the early-stage MALT lymphoma as was performed in the present case. CONCLUSION: Since HT is associated with PTC and MALT lymphoma, patients with HT deserve careful surveillance for both disease entities. In our patient, the management of one malignancy did not affect the management of the other, and the prognosis did not seem to be affected.

Outdoor thermal comfort study in a sub-tropical climate: a longitudinal study based in Hong Kong.

This paper presents the findings of an outdoor thermal comfort study conducted in Hong Kong using longitudinal experiments--an alternative approach to conventional transverse surveys. In a longitudinal experiment, the thermal sensations of a relatively small number of subjects over different environmental conditions are followed and evaluated. This allows an exploration of the effects of changing climatic conditions on thermal sensation, and thus can provide information that is not possible to acquire through the conventional transverse survey. The paper addresses the effects of changing wind and solar radiation conditions on thermal sensation. It examines the use of predicted mean vote (PMV) in the outdoor context and illustrates the use of an alternative thermal index--physiological equivalent temperature (PET). The paper supports the conventional assumption that thermal neutrality corresponds to thermal comfort. Finally, predictive formulas for estimating outdoor thermal sensation are presented as functions of air temperature, wind speed, solar radiation intensity and absolute humidity. According to the formulas, for a person in light clothing sitting under shade on a typical summer day in Hong Kong where the air temperature is about 28°C and relative humidity about 80%, a wind speed of about 1.6 m/s is needed to achieve neutral thermal sensation.

Pregnancy and acromegaly: a review.

To review the literature regarding the diagnosis and management of acromegaly during pregnancy. A systematic literature search was performed using MEDLINE including hand-searching reference lists from original articles. The diagnosis of acromegaly during pregnancy is made difficult due to the physiologic changes in pituitary GH secretion and IGF-1 production resulting from placental GH secretion and the inability of commercial assays to discriminate between pituitary and placental GH. Most patients with acromegaly during pregnancy do not have an increase in tumor size, metabolic complications are uncommon, and neonatal outcome is largely unaffected. IGF-1 levels tend to be stable in such patients possibly due to the high estrogen levels causing GH resistance. Dopamine agonists, somatostatin analogues, and a GH receptor antagonist have been reported to be safe during pregnancy. Patients with visual field defects should be considered for surgery, but in most cases this can be safely postponed until after delivery. Overall, pregnancy in acromegaly is uneventful and newborns unaffected. Dopamine agonists and somatostatin analogues have not been associated with major adverse effects to the fetus; however, more data are needed to validate their safety.

The HIV-1 Vpu viroporin inhibitor BIT225 does not affect Vpu-mediated tetherin antagonism.

Among its many roles, the HIV-1 accessory protein Vpu performs a viroporin function and also antagonizes the host cell restriction factor tetherin through its transmembrane domain. BIT225 is a small molecule inhibitor that specifically targets the Vpu viroporin function, which, in macrophages, resulted in late stage inhibition of virus release and decreased infectivity of released virus, a phenotype similar to tetherin-mediated restriction. Here, we investigated whether BIT225 might mediate its antiviral function, at least in part, via inhibition of Vpu-mediated tetherin antagonism. Using T-cell lines inducible for tetherin expression, we found that BIT225 does not exert its antiviral function by inhibiting Vpu-mediated tetherin downmodulation from the cell surface, the main site of action of tetherin activity. In addition, results from a bioluminescence resonance energy transfer (BRET) assay showed that the Vpu-tetherin interaction was not affected by BIT225. Our data provide support for the concept that tetherin antagonism and viroporin function are separable on the Vpu transmembrane and that viroporin function might be cell-type dependent. Further, this work contributes to the characterization of BIT225 as an inhibitor that specifically targets the viroporin function of Vpu.

Hyperandrogenism in a postmenopausal woman: diagnostic and therapeutic challenges.

OBJECTIVE: To describe a postmenopausal woman with severe hyperandrogenism who responded dramatically to a gonadotropin-releasing hormone (GnRH) agonist. METHODS: Detailed clinical and laboratory findings are presented, and the pertinent literature is reviewed. RESULTS: A 53-year-old postmenopausal woman with end-stage renal disease, who had undergone kidney transplantation, was referred because of high serum testosterone levels. She presented with worsening acne and hirsutism for the previous 2 years. Her medications included prednisone (7.5 mg every other day). On examination, mild facial acne and hirsutism but no virilizing features were noted. Laboratory results showed generous postmenopausal gonadotropin levels and markedly elevated total and free testosterone levels, which failed to suppress with a 2-day low-dose dexamethasone test. Transvaginal ultrasonography and a computed tomographic scan failed to identify an ovarian or adrenal abnormality. Administration of a GnRH agonist (Depo-Lupron) resulted in a dramatic decline in follicle-stimulating hormone, luteinizing hormone, and testosterone levels after 1 month, which persisted during the course of 11 months of therapy. The source of marked hyperandrogenism in postmenopausal women represents a diagnostic challenge. The absence of a tumor on diagnostic imaging and the inability to perform catheterization studies confound the problem. Androgen levels did not suppress with glucocorticoids. We reasoned that a clear response to a GnRH agonist would indicate a nontumorous ovarian source of hyperandrogenism. Regrettably, the literature has described cases of ovarian tumors and, rarely, adrenal adenomas that are responsive to gonadotropins. CONCLUSION: The striking improvement in a postmenopausal woman with severe hyperandrogenism by means of GnRH agonist therapy demonstrates its potential use in poor surgical candidates without necessarily delineating the source of androgen excess.

Tetherin and its viral antagonists.

Restriction factors comprise an important layer of host defense to fight against viral infection. Some restriction factors are constitutively expressed whereas the majority is induced by interferon to elicit innate immunity. In addition to a number of well-characterized interferon-inducible antiviral factors such as RNaseL/OAS, ISG15, Mx, PKR, and ADAR, tetherin (BST-2/CD317/HM1.24) was recently discovered to block the release of enveloped viruses from the cell surface, which is regarded as a novel antiviral mechanism induced by interferon. Here, we briefly review the history of tetherin discovery, discuss how tetherin blocks virus production, and highlight the viral countermeasures to evade tetherin restriction.

Weight considerations in pharmacotherapy for type 2 diabetes.

Obesity has been increasing in prevalence worldwide and the majority of patients with type 2 diabetes are either overweight or obese. Diabetes management in this population has been difficult since a number of antidiabetes agents are associated with weight gain. The effects of various antidiabetes agents and antiobesity agents on glycemic control and body weight will be reviewed. Briefly, sulfonylureas, thiazolidinediones, and insulin are associated with weight gain, whereas metformin and amylin analogs are weight neutral or associated with modest weight loss. Dipeptidyl-peptidase-4 inhibitors are weight neutral, whereas glucagon-like peptide-1 analogs are associated with weight loss. The effect of orlistat and sibutramine in type 2 diabetes is also evaluated. The treatment of diabetes should not only focus on glycemic control as its sole intention, but it should factor in the effect of these various agents on weight, as well, since obesity aggravates insulin resistance, beta cell failure, and cardiovascular risk.

Acute kidney injury predicts outcomes of non-critically ill patients.

OBJECTIVE: To evaluate whether acute kidney injury (AKI), defined as an increase in the serum creatinine level of 0.3 mg/dL or more within 48 hours, predicts outcomes of non-critically ill patients. PATIENTS AND METHODS: Among the adults admitted from June 1, 2005, to June 30, 2007, to the medical wards of a community teaching hospital, 735 patients with AKI and 5089 controls were identified. Demographic and health information, serum creatinine values, and outcomes were abstracted from patients' computerized medical records. Outcomes of patients with AKI were compared with those of controls. In an additional case-control analysis, more detailed clinical information was abstracted from the medical records of 282 pairs of randomly selected, age-matched AKI cases and controls. Conditional multivariate logistic regression analyses were used to adjust for potential confounders of AKI effect on outcomes. RESULTS: Overall, patients with AKI had higher in-hospital mortality (14.8% vs 1.5%; P<.001), longer lengths of stay (median 7.9 vs 3.7 days; P<.001), and higher rates of transfer to critical care areas (28.6% vs 4.3%; P<.001); survivors were more likely to be discharged to an extended care facility (43.1% vs 20.3%; P<.001). Conditional multivariate logistic regression analyses of the 282 pairs of cases and controls showed that patients with AKI were 8 times more likely to die in hospital (odds ratio [OR], 7.9; 95% CI [confidence interval], 2.9-15.3) and were 5 times more likely to have prolonged (>or=7 days) hospital stays (OR, 5.2; 95% CI, 3.5-7.9) and require intensive care (OR, 4.7; 95% CI, 2.7-8.1), after adjustment for age, comorbidities, and other potential confounders. CONCLUSION: In this study, AKI was associated with adverse outcomes in non-critically ill patients.