Targeting Features of the Metabolic Syndrome Through Sympatholytic Effects of SGLT2 Inhibition.

PURPOSE OF REVIEW: The moderate glucose-lowering effect of sodium glucose co-transporter 2 (SGLT2) inhibitors is unlikely to explain SGLT2 inhibitor-mediated beneficial outcomes, and unravelling the underlying mechanisms is a high priority in the research community. Given the dominant pathophysiologic role of the sympathetic nervous system activation in conditions such as hypertension and perturbed glucose homeostasis, it is pertinent to postulate that SGLT2 inhibitors may exert their beneficial effects at least in part via sympathetic inhibition. RECENT FINDINGS: SGLT2 inhibitors have shown enormous potential to improve cardiovascular outcomes in patients with type 2 diabetes, and their therapeutic potential is currently being investigated in a range of associated comorbidities such as heart failure and chronic kidney disease. Indeed, recent experimental data in relevant animal models highlight a bidirectional interaction between sympathetic nervous system activation and SGLT2 expression, and this facilitates several of the features associated with SGLT2 inhibition observed in clinical trials including improved glucose metabolism, weight loss, increased diuresis, and lowering of blood pressure. Currently available data highlight the various levels of interaction between the sympathetic nervous system and SGLT2 expression and explores the potential for SGLT2 inhibition as a therapeutic strategy in conditions commonly characterised by sympathetic activation.

Could Sodium/Glucose Co-Transporter-2 Inhibitors Have Antiarrhythmic Potential in Atrial Fibrillation? Literature Review and Future Considerations.

The global burden of atrial fibrillation (AF) is constantly increasing, necessitating novel and effective therapeutic options. Sodium glucose co-transporter 2 (SGLT2) inhibitors have been introduced in clinical practice as glucose-lowering medications. However, they have recently gained prominence for their potential to exert substantial cardiorenal protection and are being evaluated in large clinical trials including patients with type 2 diabetes and normoglycemic adults. In this review we present up-to-date available evidence in a pathophysiology-directed manner from cell to bedside. Preclinical and clinical data regarding a conceivable antiarrhythmic effect of SGLT2 inhibitors are beginning to accumulate. Herein we comprehensively present data that explore the potential pathophysiological link between SGLT2 inhibitors and AF. With regard to clinical data, no randomized controlled trials evaluating SGLT2 inhibitors effects on AF as a pre-specified endpoint are available. However, data from randomized controlled trial post-hoc analysis as well as observational studies point to a possible beneficial effect of SGLT2 inhibitors on AF. Meta-analyses addressing this question report inconsistent results and the real magnitude of AF prevention by SGLT2 inhibition remains unclear. Still, while (i) pathophysiologic mechanisms involved in AF might be favorably affected by SGLT2 inhibitors and (ii) emerging, yet inconsistent, clinical data imply that SGLT2 inhibitor-mediated cardiorenal protection could also exert antiarrhythmic effects, the argument of whether these novel drugs will reduce AF burden is unsettled and mandates appropriately designed and adequately sized randomized controlled studies.

Prolonged ketamine infusion modulates limbic connectivity and induces sustained remission of treatment-resistant depression.

Ketamine produces a rapid antidepressant response in over 50% of adults with treatment-resistant depression. A long infusion of ketamine may provide durable remission of depressive symptoms, but the safety, efficacy, and neurobiological correlates are unknown. In this open-label, proof-of-principle study, adults with treatment-resistant depression (N = 23) underwent a 96-h infusion of intravenous ketamine (0.15 mg/kg/h titrated toward 0.6 mg/kg/h). Clonidine was co-administered to reduce psychotomimetic effects. We measured clinical response for 8 weeks post-infusion. Resting-state functional magnetic resonance imaging was used to assess functional connectivity in patients pre- and 2 weeks post-infusion and in matched non-depressed controls (N = 27). We hypothesized that responders to therapy would demonstrate response-dependent connectivity changes while all subjects would show treatment-dependent connectivity changes. Most participants completed infusion (21/23; mean final dose 0.54 mg/kg/h, SD 0.13). The infusion was well tolerated with minimal cognitive and psychotomimetic side effects. Depressive symptoms were markedly reduced (MADRS 29 ± 4 at baseline to 9 ± 8 one day post-infusion), which was sustained at 2 weeks (13 ± 8) and 8 weeks (15 ± 8). Imaging demonstrated a response-dependent decrease in hyperconnectivity of the subgenual anterior cingulate cortex to the default mode network, and a treatment-dependent decrease in hyperconnectivity within the limbic system (hippocampus, amygdala, medial thalamus, nucleus accumbens). In exploratory analyses, connectivity was increased between the limbic system and frontal areas, and smaller right hippocampus volume at baseline predicted larger MADRS change. A single prolonged infusion of ketamine provides a tolerated, rapid, and sustained response in treatment-resistant depression and normalizes depression-related hyperconnectivity in the limbic system and frontal lobe. ClinicalTrials.gov : Treatment Resistant Depression (Pilot), NCT01179009.

Postoperative ileus-An ongoing conundrum.

BACKGROUND: Postoperative ileus is common and is a major clinical problem. It has been widely studied in patients and in experimental models in laboratory animals. A wide variety of treatments have been tested to prevent or modify the course of this disorder. PURPOSE: This review draws together information on animal studies of ileus with studies on human patients. It summarizes some of the conceptual advances made in understanding the mechanisms that underlie paralytic ileus. The treatments that have been tested in human subjects (both pharmacological and non-pharmacological) and their efficacy are summarized and graded consistent with current clinical guidelines. The review is not intended to provide a comprehensive overview of ileus, but rather a general understanding of the major clinical problems associated with it, how animal models have been useful to elucidate key mechanisms and, finally, some perspectives from both scientists and clinicians as to how we may move forward with this debilitating yet common condition.

The Effectiveness of Non-Benzodiazepine, Non-Barbiturate Medications for Alcohol Withdrawal Syndrome: A Rapid Systematic Review.

AIM: There are potential clinical, ethical and legal concerns with overdosing benzodiazepines (or barbiturates) for the treatment of moderate to severe alcohol withdrawal symptoms (AWS) through telemedicine or ambulatory outpatients. A rapid systematic review to (a) qualitatively summarize the non-benzodiazepine treatment alternatives, (b) evaluate the quality of evidence for the same to effectively manage moderate to severe AWS. METHODS: We conducted searches on PubMed (January 1990 to 31 March 2020), Cochrane Central Register of Controlled Trials, and Google Scholar. We selected the English language randomized controlled trials (RCTs) assessing the efficacy and adverse effects of non-benzodiazepine and non-barbiturate medications among adults with a diagnosis of AWS. Data extraction was done in a predefined format. Risk of bias (RoB) assessment and qualitative synthesis of evidence was done with the RoB2 tool and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) proGDT. RESULTS: Thirty-four RCTs were included. Gabapentin (n = 6), carbamazepine (n = 5), baclofen (n = 5), valproate (n = 3), clonidine/lofexidine (n = 3) and acamprosate (n = 2) had more than one trial with a particular comparison group. Four studies were found to have a low ROB. The GRADE evidence summary showed gabapentin had a 'moderate' level of evidence against standard benzodiazepine treatments for reducing the severity of AWS. The level of certainty was 'low' for carbamazepine, baclofen and valproate and 'very low' for acamprosate and clonidine/lofexidine. Reported adverse events between these alternative medications and benzodiazepines or placebo were generally unremarkable. CONCLUSIONS: Although benzodiazepines remain the treatment of choice for AWS, during particular circumstances, gabapentin could be an alternative although like benzodiazepines is not without risk when used in the community. Future RCTs must aim to improve upon the quality of evidence.

Fabry disease with early-onset ventricular dilation: A case report.

RATIONALE: The most common cardiac involvement of Fabry disease (FD) is left ventricular hypertrophy (LVH), which usually occurs in male patients over the age of 30. In rare cases, it can progress to ventricular dilation in the late stage of the disease. PATIENT CONCERNS: A 16-year-old boy presenting with recurrent extremity pain and chest distress was admitted to our hospital. Imaging examinations revealed ventricular dilation. DIAGNOSIS: α-Galactosidase A enzyme assay and GLA gene sequencing confirmed the diagnosis of FD and revealed a novel mutation c.76_77insT. INTERVENTIONS: The patient was treated using metoprolol (23.75 mg qd) and angiotensin-converting enzyme inhibitor (fosinopril sodium 5 mg qd). He refused enzyme replacement therapy for financial reasons. OUTCOMES: The echocardiography, electrocardiography, renal function, and routine blood and urine tests performed 20 months after the patients discharge from hospital showed no significant changes. The patient reported a slow and gradual decrease in the frequency and degree of pain and chest distress, starting approximately 24 months after discharge. LESSONS: Cardiac involvement of FD can progress rapidly in some cases. Screening for FD should be considered in patients with unexplained ventricular dilation, especially in those with a history of typical FD manifestations.

Screening Rates for Primary Aldosteronism in Resistant Hypertension: A Cohort Study.

Resistant hypertension is associated with higher rates of cardiovascular disease, kidney disease, and death than primary hypertension. Although clinical practice guidelines recommend screening for primary aldosteronism among persons with resistant hypertension, rates of screening are unknown. We identified 145 670 persons with hypertension and excluded persons with congestive heart failure or advanced chronic kidney disease. Among this cohort, we studied 4660 persons ages 18 to <90 from the years 2008 to 2014 with resistant hypertension and available laboratory tests within the following 24 months. The screening rate for primary aldosteronism in persons with resistant hypertension was 2.1%. Screened persons were younger (55.9±13.3 versus 65.5±11.6 years; P<0.0001) and had higher systolic (145.1±24.3 versus 139.6±20.5 mm Hg; P=0.04) and diastolic blood pressure (81.8±13.6 versus 74.4±13.8 mm Hg; P<0.0001), lower rates of coronary artery disease (5.2% versus 14.2%; P=0.01), and lower serum potassium concentrations (3.9±0.6 versus 4.1±0.5 mmol/L; P=0.04) than unscreened persons. Screened persons had significantly higher rates of prescription for calcium channel blockers, mixed α/ß-adrenergic receptor antagonists, sympatholytics, and vasodilators, and lower rates of prescription for loop, thiazide, and thiazide-type diuretics. The prescription of mineralocorticoid receptor antagonists or other potassium-sparing diuretics was not significantly different between groups (P=0.20). In conclusion, only 2.1% of eligible persons received a screening test within 2 years of meeting criteria for resistant hypertension. Low rates of screening were not due to the prescription of antihypertensive medications that may potentially interfere with interpretation of the screening test. Efforts to highlight guideline-recommended screening and targeted therapy are warranted.

Resistant and refractory hypertension: two sides of the same disease? / Hipertensão resistente e refratária: duas faces de uma mesma doença?

Abstract Refractory hypertension (RfH) is an extreme phenotype of resistant hypertension (RH), being considered an uncontrolled blood pressure besides the use of 5 or more antihypertensive medications, including a long-acting thiazide diuretic and a mineralocorticoid antagonist. RH is common, with 10-20% of the general hypertensives, and its associated with renin angiotensin aldosterone system hyperactivity and excess fluid retention. RfH comprises 5-8% of the RH and seems to be influenced by increased sympathetic activity. RH patients are older and more obese than general hypertensives. It is strongly associated with diabetes, obstructive sleep apnea, and hyperaldosteronism status. RfH is more frequent in women, younger patients and Afro-americans compared to RFs. Both are associated with increased albuminuria, left ventricular hypertrophy, chronic kidney diseases, stroke, and cardiovascular diseases. The magnitude of the white-coat effect seems to be higher among RH patients. Intensification of diuretic therapy is indicated in RH, while in RfH, therapy failure imposes new treatment alternatives such as the use of sympatholytic therapies. In conclusion, both RH and RfH constitute challenges in clinical practice and should be addressed as distinct clinical entities by trained professionals who are capable to identify comorbidities and provide specific, diversified, and individualized treatment.

Resumo A Hipertensão Arterial Refratária (HARf) representa um fenótipo extremo da hipertensão arterial resistente (HAR), sendo considerada a falência ao tratamento apesar do uso de 5 ou mais classes de anti-hipertensivos, incluindo um diurético tiazídico de longa ação e um antagonista mineralocorticoide. A HAR é comum (10-20%) entre os hipertensos em geral, sendo decorrente de hiperatividade do Sistema Renina Angiotensina Aldosterona e retenção hidrossalina. Aqueles com HARf correspondem a 5-8% dos resistentes e parecem sofrer maior influência catecolaminérgica. Os resistentes tendem a ter maior idade, ao sobrepeso e à obesidade. Comorbidades incluem diabetes, apneia obstrutiva do sono e status de hiperaldosteronismo. Refratários são afro-americanos em maior proporção, mais jovens e, predominantemente, mulheres. Ambos são fortemente associados à elevada albuminúria, HVE, doenças cardio e cerebrovasculares, além da doença renal crônica. O fenômeno do jaleco branco parece ser mais evidente nos resistentes. Quanto ao tratamento, a intensificação da terapia diurética está indicada nos resistentes, enquanto na HARf, a falência à terapia impôs novas alternativas de tratamento ("simpaticolíticas"). Em conclusão, tanto a HAR quanto a HARf constituem-se desafios na prática clínica e devem ser abordadas como entidades clínicas distintas por profissionais especialistas que identifiquem comorbidades e venham a prover um tratamento específico, diversificado e individualizado.

Quality of life improves in vasovagal syncope patients after clinical trial enrollment regardless of fainting in follow-up.

BACKGROUND: Frequent syncope is linked to poorer health-related quality of life (HRQoL). Recurrent syncope has been observed to reduce in all groups after seeing a syncope expert and enrolling in a clinical trial. It is unknown if HRQoL improves with this reduction in syncope recurrence. OBJECTIVES: We examined the change in HRQoL over time in vasovagal syncope (VVS) patients seen by a syncope expert and enrolled in a trial. We also explored whether change differed with treatment or the frequency of fainting during follow up. METHODS: The Short Form Health Survey (SF36) was completed at baseline (BL), 6 m, and 12 m post-enrollment by VVS patients in the 1st and 2nd Prevention of Syncope Trials, which were multi-centered, randomized, placebo-controlled trials of metoprolol (POST) and fludrocortisone (POST2). Differences in HRQoL at BL, 6 m, and 12 m were analyzed and compared by faints in follow-up and randomization group. RESULTS: Complete study data were available for 143 VVS patients (40 ±â€¯17 years, 62% F). Over 12 months, patients reported improvement in all SF36 dimensions except for bodily pain. Post hoc analyses indicated that differences first occurred between BL and 6 m for all but general health. Fainting in follow-up or drug randomization group did not diminish the improvements. The baseline syncope burden was not different whether patients' HRQoL improved or not. CONCLUSION: HRQoL of VVS patients improves over time after enrolling in a clinical trial, even with recurrent faints or randomization to placebo. Improvements may result from alternative factors, such as interaction with experts or patient adjustment.

Rapid transition from methadone to buprenorphine using naltrexone-induced withdrawal: A case report.

Background: Patients taking methadone for opioid use disorder may desire transition to buprenorphine for a number of reasons. However, the current recommended approach for this transition generally takes weeks to months as an outpatient, causing considerable discomfort to the patient and a heightened risk of relapse during the transition period. Case: We describe the case of a patient on methadone maintenance who was rapidly transitioned to buprenorphine because of her desire to not return to her methadone clinic. In order to rapidly transition the patient from methadone to buprenorphine, naltrexone was administered to precipitate acute opioid withdrawal, which was followed soon after by buprenorphine induction. Discussion: Rapid transition from methadone maintenance to buprenorphine can be accomplished in inpatients by precipitating acute withdrawal with naltrexone, providing an effective alternative for patients who cannot tolerate the typical protracted methadone taper required prior to buprenorphine induction as an outpatient.

Treatment of Resistant and Refractory Hypertension.

Resistant hypertension (RHTN) is defined as uncontrolled blood pressure despite the use of ≥3 antihypertensive agents of different classes, including a diuretic, usually thiazide-like, a long-acting calcium channel blocker, and a blocker of the renin- angiotensin system, either an ACE (angiotensin-converting enzyme) inhibitor or an ARB (angiotensin receptor blocker), at maximal or maximally tolerated doses. Antihypertensive medication nonadherence and the white coat effect, defined as elevated blood pressure when measured in clinic but controlled when measured outside of clinic, must be excluded to make the diagnosis. RHTN is a high-risk phenotype, leading to increased all-cause mortality and cardiovascular disease outcomes. Healthy lifestyle habits are associated with reduced cardiovascular risk in patients with RHTN. Aldosterone excess is common in patients with RHTN, and addition of spironolactone or amiloride to the standard 3-drug antihypertensive regimen is effective at getting the blood pressure to goal in most of these patients. Refractory hypertension is defined as uncontrolled blood pressure despite use of ≥5 antihypertensive agents of different classes, including a long-acting thiazide-like diuretic and an MR (mineralocorticoid receptor) antagonist, at maximal or maximally tolerated doses. Fluid retention, mediated largely by aldosterone excess, is the predominant mechanism underlying RHTN, while patients with refractory hypertension typically exhibit increased sympathetic nervous system activity.

Resistant and refractory hypertension: two sides of the same disease?

Refractory hypertension (RfH) is an extreme phenotype of resistant hypertension (RH), being considered an uncontrolled blood pressure besides the use of 5 or more antihypertensive medications, including a long-acting thiazide diuretic and a mineralocorticoid antagonist. RH is common, with 10-20% of the general hypertensives, and its associated with renin angiotensin aldosterone system hyperactivity and excess fluid retention. RfH comprises 5-8% of the RH and seems to be influenced by increased sympathetic activity. RH patients are older and more obese than general hypertensives. It is strongly associated with diabetes, obstructive sleep apnea, and hyperaldosteronism status. RfH is more frequent in women, younger patients and Afro-americans compared to RFs. Both are associated with increased albuminuria, left ventricular hypertrophy, chronic kidney diseases, stroke, and cardiovascular diseases. The magnitude of the white-coat effect seems to be higher among RH patients. Intensification of diuretic therapy is indicated in RH, while in RfH, therapy failure imposes new treatment alternatives such as the use of sympatholytic therapies. In conclusion, both RH and RfH constitute challenges in clinical practice and should be addressed as distinct clinical entities by trained professionals who are capable to identify comorbidities and provide specific, diversified, and individualized treatment.

Effect of Sympatholytic Therapy on Circadian Cardiac Autonomic Activity in Non-Diabetic Chronic Kidney Disease.

Although beta-blockade itself is not a first choice for chronic kidney disease (CKD) patients, alpha-beta-blockers (ABB) do improve their prognoses. This study's aim was to evaluate the effect of beta-selective-blockers (BSB) and ABB on circadian cardiac autonomic activity in CKD patients.The study consisted of 496 non-diabetic individuals who underwent 24-hour Holter monitoring (149 CKD patients and 347 controls without CKD). Using heart rate variability analysis, we evaluated the proportion of NN50 and the high-frequency component (reflecting parasympathetic activity), and low- to high-frequency ratio (reflecting sympathovagal balance). These indices were evaluated by regression analysis incorporating gender, age, related comorbidities, and medications. BSB increased vagal activity only in the day-time and not the night-time in controls. In CKD patients, BSB was significantly related to higher vagal activity throughout the day and with lower sympathovagal balance at night. The night sympathovagal balance of CKD patients taking ABB was significantly higher than that of CKD patients taking BSB, which was the only significant difference between the effects of BSB and ABB.The sympatholytic therapy effect is different depending on CKD presence and whether patients are treated with BSB or ABB. In CKD patients without severe heart failure, BSB could be associated with higher parasympathetic activity and lower sympathovagal balance compared to ABB.

Effect of a Stellate Ganglion Block on Acute Lung Injury in Septic Rats.

A stellate ganglion block (SGB) is a clinical sympathetic block which can inhibit the body systemic inflammatory response. However, whether and how SGB can attenuate the sepsis-induced acute lung injury remains unclear. Here, we evaluated the effect of SGB on sepsis-induced acute lung injury in rats. Ninety healthy Sprague Dawley (SD) male rats were divided into three groups: the sham operation group (S group), sepsis group (Sep group), and SGB group. The sepsis model rats were produced by cecum ligation and puncture (CLP), and blood samples were taken from the abdominal aorta of the rats at different time points for evaluating the concentration of TNF-α, IL-6, and IL-10 by enzyme-linked immunosorbent assay (ELISA). The rats were sacrificed, and lungs were collected to measure the wet/dry (W/D) lung tissue weight ratio, score the lung tissue pathological damage by microscopic examination, determine the myeloperoxidase (MPO) activity by spectrophotometry, and measure nuclear factor-kappa B (NF-κB) p65 expression by Western blot. The concentration of serum TNF-α, IL-6, and IL-10, lung tissue W/D ratio, pathological injury score, MPO activity, and expression of NF-κB p65 were higher in the Sep group compared with the S group at T1-4. Furthermore, the concentration of serum TNF-α and IL-6, lung tissue W/D ratio, pathological damage score, MPO activity, and expression of NF-κB p65 were reduced and the concentration of IL-10 was increased in the SGB group compared with the Sep group at T1-4. The successful sepsis model rats were induced by CLP, and SGB attenuated the sepsis-induced acute lung injury in rats.

Misdirected Sympathy: The Role of Sympatholysis in Sepsis and Septic Shock.

The spectrum of sepsis and septic shock remains a highly prevalent disease state, carrying a high risk of morbidity and mortality. The sympathetic nervous system (SNS) plays an important role in this initial cascade, enabling the host to respond to invading pathogens; however, prolonged activation can become pathological. The potential for unregulated sympathetic tone to become of detriment in patients with sepsis has fueled interest in the role and impact of sympatholysis, the selective inhibition of sympathetic tone. The cornerstone of septic shock therapy for decades has been the supplementation of catecholamines and thus potential further perpetuation of this sympathetic dysregulation. Although the theory of sympatholysis circulates around cardiovascular effects and stroke volume optimization, the impact of augmenting the SNS may extend well beyond this, including the impacts on the immune system, inflammatory cascade, and even gene transcription. Presently, the most robust clinical evidence involves the use of the cardioselective ß-blocker esmolol in patients with septic shock with persistent tachycardia secondary to catecholamine use. Evidence is isolated only to animal models with α-agonists. Future evidence stands to elucidate the balance of sympathetic and autonomic tone as well as the potential role of redirecting and maximizing sympathetic activity.

Superior oblique myokymia treated with levobunolol.

Superior oblique myokymia (SOM) is an uncommon condition of unclear etiology that results in episodes of oscillopsia and diplopia. There is no established treatment protocol for SOM. We present 2 cases of SOM successfully managed with topical levobunolol 0.5%; both patients responded to a short course of medication administration and required minimal ongoing therapy. Case 1 was a 69-year-old woman with left SOM who had previously undergone a left Harada-Ito procedure. Her SOM improved immediately on administration of levobunolol and was maintained at follow-up 1 year later. Case 2 was a 49-year-old man with right SOM that affected his ability to work. After 2 days of topical levobunolol 0.5% nightly in the right eye, SOM episodes ceased; he continues to use drops intermittently for occasional recurrences.

CT-Guided, Percutaneous Ethanol Sympatholysis for Primary Hyperhidrosis.

PURPOSE: Primary hyperhidrosis (PH) typically involves the craniofacial (CF) or axillary-palmar (AP) region. Our purpose was to determine the safety and efficacy of CT-guided sympatholysis for treating PH. METHODS: In this prospective study, 39 consecutive patients with CF or AP PH were referred for percutaneous sympatholysis. Procedures were performed under CT guidance and minimal sedation. We treated level T2 for CF hyperhidrosis and T2, T3, and T4 for AP hyperhidrosis. Twenty-two-gauge spinal needles were placed bilaterally at the anterolateral surface of the vertebral body. After infiltration of lidocaine (2 mL), a neurological test was performed to exclude Horner syndrome. Neurolysis was effected with ethanol (2 mL) via each needle. Patients were discharged 1 h postoperatively and followed up at 1 week, 1 month, and then as clinically indicated. Disease-free Kaplan-Meier curves were compared using log-rank tests. Complications were categorized according to Common Terminology Criteria for Adverse Events. RESULTS: One patient failed the lidocaine test and was excluded. Of the 38 patients included in this cohort (16 men), mean age was 38 years (range 18-61), and mean follow-up was 18 months (range 1-36). Technical success for these 38 patients was 100%. Seventeen patients had symptom recurrence, 14 of whom were retreated. Efficacy was 72% for CF hyperhidrosis, 50% for AP hyperhidrosis, and 60% overall. There were three major complications (two pneumothoraces, one severe intercostal neuralgia requiring medication). CONCLUSIONS: CT-guided sympatholysis for CF or AP PH had 18-month efficacy rates of 72 and 50%, with a favorable risk profile. LEVEL OF EVIDENCE: Level 2b.

Autonomic Reflex Screen Test Abnormalities in Cold-Induced Sweating Syndrome Type 1.

Cold-induced sweating syndrome (CISS) is a rare autosomal recessive disease due to mutation in the Cytokine receptor-like factor 1 (CRLF1). The characteristic symptom of CISS is the tendency to sweat profusely especially in the upper body and hands when the patient is exposed to cold temperature. We sought to first report the findings of autonomic reflex screen in a case of CISS type 1 with Cytokine receptor-like factor 1 mutation. Valsalva morphology, Valsalva ratio, and heart rate response to deep breathing were normal for the patient's age. Quantitative sudomotor axon reflex test showed nonlength dependent decrease in the sweat volume. Tilt table revealed evidence of reflex (vasovagal) "syncope," however, the patient was asymptomatic without loss of consciousness.

Protective Effects of Bisoprolol against Acute Exacerbation in Moderate-to-Severe Chronic Obstructive Pulmonary Disease.

Although recent retrospective studies suggested that the use of ß-blockers appears to help improve the mortality rate and decrease the rate of exacerbation in chronic obstructive pulmonary disease (COPD) patients with heart failure, the effects of ß-blockers on COPD patients without heart failure have not been established. Based on previous reports, we have launched a multicenter, prospective, single-arm phase II study to evaluate the preventive effect of the cardioselective ß-blocker bisoprolol in COPD exacerbation, in Japanese individuals with moderate-to-severe COPD who do not have heart failure but do have hypertension requiring the use of medication. The primary endpoint is the rate of mild-to-severe COPD exacerbation. The results of this study will clarify whether bisoprolol can prevent exacerbation in COPD patients without heart failure.