Morvan's Syndrome: The Importance of Knowing Different Risk-Associated Phenotypes and Antibodies in Identifying the Correct Underlying Tumor.

Paraneoplastic neurologic syndromes (PNS) are neurologic disorders that can affect any part of the nervous system, occur in association with cancer, and have an immune-mediated mechanism that produces direct damage to the neural tissue. Neurological symptoms frequently precede, in months to years, the symptoms directly attributed to the primary tumor, requiring a high clinical suspicion for adequate investigation. We report the case of a man in his early 80s admitted for an altered level of consciousness, alternating between periods with stupor and drowsiness, short-term waking states and psychomotor agitation, respiratory failure and dysautonomia, resembling a Morvan's syndrome. Anti-leucine-rich glioma-inactivated 1 and anti-contactin-associated protein-like 2 antibodies were both positive and, after exclusion of infectious and autoimmune systemic causes, the possibility of PNS was raised. Screening for the primary tumor was pursued, and an 18F-fluorodeoxyglucose (18F-FDG)/PET showed only an intensely hypermetabolic, apparent parietal thickening of the lower rectum. Due to the frequent association of Morvan's syndrome to thymoma, a review of the CT of the thorax images was requested and a mediastinal image with features of thymoma was identified. PNS treatment and prognosis depend on finding and treating the underlying tumor, with benefits in both resolution of neurological symptoms and in the prognosis of the underlying tumor itself. Therefore, clinicians should be aware of this frequent but underdiagnosed and underreported condition, in order to improve the chances of better outcomes.

Severe Pneumonia Caused by SARS-CoV-2: A Novel Cause of Platypnoea-Orthodeoxia Syndrome.

Platypnoea-orthodeoxia syndrome (POS) is a condition characterized by dyspnoea and hypoxaemia while sitting or standing, which improves during decubitus. It is usually caused by intracardiac right-to-left shunting through a patent foramen ovale but may also occur due to pulmonary ventilation-perfusion mismatch of other aetiologies. A new cause of POS was recently described: SARS-CoV-2 pneumonia. We report the case of a 62-year-old man admitted for SARS-CoV-2 pneumonia with respiratory failure. Chest computed tomography angiography showed pulmonary thromboembolism and parenchymal lung changes compatible with COVID-19. He had worsening dyspnoea in a sitting position, relieved by assuming the dorsal position. He was diagnosed with POS after other causes were excluded. POS is an underdiagnosed complication of COVID-19 and is manageable with respiratory rehabilitation. LEARNING POINTS: Platypnoea-orthodeoxia syndrome is an under-recognized condition presenting as a complication of a structural shunt.We describe SARS-CoV-2 pneumonia as a novel cause for this syndrome.It is a reversible syndrome provided there is early diagnosis and initiation of pulmonary rehabilitation.

Does the Same Hyperlactatemia Cut-Off in the Context of Acute Diseases Hold the Same Meaning in Diabetes Mellitus?

Background Hyperlactatemia is defined by a lactate concentration of >2 mmol/L, and a lactate concentration of above >4 mmol/L is commonly used to define severe hyperlactatemia. It is a common disorder in critically ill patients and is associated with adverse prognosis. Diabetes mellitus(DM) can also be associated with increased lactate levels at baseline. In this study, we aimed to document the development of severe hyperlactatemia in acute situations among patients with and without DM, to analyze potential contributors to lactate elevation and their impact on mortality, and to analyze whether lactate concentrations of >4 mmol/L have equal prognostic significance in patients with and without DM. Methodology A retrospective, cross-sectional study was performed among patients admitted to our internal medicine wards in the context of acute disease with lactate concentrations of ​​≥2 mmol/L. Data were collected regarding age, sex, highest lactate concentrations, cause of hyperlactatemia, DM, and mortality. Statistical analysis was performed using SPSS version 23. Results In total, 151 patients with lactate levels of ≥2 mmol/L were analyzed. The mean age of the patients was 78.2 ± 14.9 years, and 55% of the patients were female. Overall, 55.6% of the patients had DM, as well as higher lactatemia of 6.3 ± 3.4 mmol/L (vs 5.1 ± 3.2 in non-DM patients, p = 0.003), with the majority reaching values of >4 mmol/L (vs 34.8% in non-DM patients). When potential contributors to the development of severe hyperlactatemia (lactate >4 mmol/L) were analyzed in DM patients, metformin consumption concomitantly with factors potentiating its accumulation, sepsis/septic shock, ischemia, and neoplasia were the most frequently identified contributors. In non-DM patients, the three former factors were also the most frequently reported. The 30-day mortality rate was 25.82%, with deceased patients also displaying a higher lactatemia of 6.5 ± 3.2 mmol/L (vs. 5.5 ± 3.3 mmol/L in patients who survived) (p = 0.037). In multivariate analysis, lactate values of >4 mmol/L were an independent predictor of mortality in the entire sample and in the subgroup without DM, but not in DM patients. Conclusions In our sample, patients with DM had higher lactate levels than non-DM patients. Our analysis raises the possibility that the same lactate values may not have equal capacity to assess prognosis in acute situations in patients with and without DM. Large-scale studies are needed to optimize cut-off points for lactatemia in patients with high baseline values, such as DM patients.

Primary angiosarcoma of superior vena cava: an unexpected diagnosis after an oncological emergency.

Angiosarcoma (AS) is a rare malignant tumour representing 1%-2% of all sarcomas. Primary AS of superior vena cava (SVC) was reported in two cases worldwide. We report a 69-year-old woman with neck discomfort, headache and dyspnoea for 3 months. CT angiography showed thrombosis in SVC and brachiocephalic veins resulting in an SVC syndrome. The patient began anticoagulant therapy and underwent balloon angioplasty with clinical improvement. Additionally, a positron emission tomography scan confirmed the presence of a mediastinal mass involving the SVC locally. The tumour was excised and a prosthesis was placed on the SVC. Histology revealed a heterogeneous tumour matrix, either myxoid and composed by fusiform cells with vimentin, homogeneous CD31 and a 30% Ki67 immunoexpression, supporting the diagnosis of an AS. Due to multiple complications, the patient never started chemotherapy, and after tumour recurrence, she died within 5 months after diagnosis.

Hepatosplenic T-cell lymphoma in a young immunocompetent man.

Hepatosplenic T-cell lymphoma (HSTCL) is a rare, aggressive type of peripheral T-cell lymphoma that is characterised by extranodal disease, with infiltration and proliferation of malignant T-cells within the liver, spleen and bone marrow. The authors report the case of a young immunocompetent man, who was admitted to the hospital with a history of prolonged, unexplained fever, fatigue and weight loss. Initial blood work showed mild pancytopaenia and imaging studies revealed hepatosplenomegaly. The diagnosis was challenging, initially mimicking infectious disease, and it required an extensive investigation that ultimately revealed the characteristic clinical, histopathological and cytogenetic features of HSTCL. The clinical course was aggressive, and despite multiagent chemotherapy, the patient died 4 months after the diagnosis. This case highlights the difficulty of diagnosing HSTCL and the importance of considering it in a differential diagnosis of hepatosplenomegaly in young men who present with constitutional symptoms and no lymphadenopathy.

Evaluation of trigeminal sensitivity to ammonia in asthmatics and healthy human volunteers.

Asthmatics often report the triggering or exacerbation of respiratory symptoms following exposure to airborne irritants, which in some cases may result from stimulation of irritant receptors in the upper airways inducing reflexive bronchoconstriction. Ammonia (NH3) is a common constituent of commercially available household products, and in high concentration has the potential to elicit sensory irritation in the eyes and upper respiratory tract of humans. The goal of the present study was to evaluate the irritation potential of ammonia in asthmatics and healthy volunteers and to determine whether differences in nasal or ocular irritant sensitivity to ammonia between these two groups could account for the exacerbation of symptoms reported by asthmatics following exposure to an irritant. Twenty-five healthy and 15 mild/moderate persistent asthmatic volunteers, with reported sensitivity to household cleaning products, were evaluated for their sensitivity to the ocular and nasal irritancy of NH3. Lung function was evaluated at baseline and multiple time points following exposure. Irritation thresholds did not differ between asthmatics and healthy controls, nor did ratings of odor intensity, annoyance, and irritancy following exposure to NH3 concentrations at and above the irritant threshold for longer periods of time (30 s). Importantly, no changes in lung function occurred following exposure to NH3 for any individuals in either group. Thus, despite heightened symptom reports to environmental irritants among asthmatics, the ocular and nasal trigeminal system of mild to moderate asthmatics does not appear to be more sensitive or more reactive than that of nonasthmatics, nor does short-duration exposure to ammonia at irritant levels induce changes in lung function. At least in brief exposures, the basis for some asthmatics to experience adverse responses to volatile compounds in everyday life may arise from factors other than trigeminally mediated reflexes.

Insulin sensitivity, food intake, and cravings with premenstrual syndrome: a pilot study.

OBJECTIVE: The objective of this pilot study was to evaluate possible differences in insulin sensitivity, food intake, and cravings between the follicular and luteal phases of the menstrual cycle in women with premenstrual syndrome (PMS). METHODS: Subjects were screened for PMS using the Penn Daily Symptom Rating (DSR) scale. Each subject had two overnight admissions (once in each cycle phase) to the Hospital of the University of Pennsylvania. They performed 3-day diet histories prior to each hospitalization. After admission, subjects received dinner and a snack, then were fasted until morning, when they underwent a frequently sampled intravenous glucose tolerance test (FSIGT). Insulin sensitivity was determined by Minimal Model analysis. Blinded analysis of diet histories and inpatient food intake was performed by a registered dietitian. RESULTS: There was no difference found in insulin sensitivity between cycle phases (n = 7). There were also no differences in proportions of macronutrients or total kilocalories by cycle phase, despite a marked difference in food cravings between cycle phase, with increased food cravings noted in the luteal phase (p = 0.002). Total DSR symptom scores decreased from a mean of 186 (+/-29.0) in the luteal phase to 16.6 (+/-14.2) in the follicular phase. Women in this study consumed relatively high proportions of carbohydrates (55%-64%) in both cycle phases measured. CONCLUSIONS: These findings reinforce the suggestion that although the symptom complaints of PMS are primarily confined to the luteal phase, the neuroendocrine background for this disorder may be consistent across menstrual cycle phases.

Menstrual cycle effects on insulin sensitivity in women with type 1 diabetes: a pilot study.

BACKGROUND: Many women complain of difficulty maintaining euglycemia during the luteal phase of the menstrual cycle. This pilot study's objective was to evaluate possible differences in insulin sensitivity between follicular and luteal phases in women with type 1 diabetes. METHODS: Women using insulin infusion pumps (n = 5, mean age 29.2 +/- 10.9 years, mean body mass index 24 +/- 1.8 kg/m(2)) underwent frequently sampled intravenous glucose tolerance tests during each cycle phase. Insulin sensitivity and glucose effectiveness were determined by Minimal Model analysis. RESULTS: Non-insulin-mediated glucose disposal increased during the luteal phase (0.009 +/- 0.004 min(1)) versus the follicular phase (0.005 +/- 0.003 min(1)) (P < 0.05). Although no significant differences were found in mean insulin sensitivity between follicular (0.76 +/- 0.27 x 10(4)/min(1) /microU/mL) and luteal phase (0.58 +/- 0.26 x 10(4)/min(1) /microU/ mL), three of the five subjects had a decline in insulin sensitivity. CONCLUSIONS: Elevated blood glucose during the luteal phase may increase insulin-independent glucose disposal. Some individuals appear more responsive to menstrual cycle effects on insulin sensitivity. Women should be encouraged to use available self-monitoring technology to identify possible cyclical variations in blood glucose that might require clinician review and insulin dosage adjustments.

48-h glucose infusion in humans: effect on hormonal responses, hunger and food intake.

Experimentally-induced hyperglycemia by prolonged glucose infusion allows investigation of the effects of sustained stimulation of the pancreatic beta-cell on insulin secretion and sensitivity. Hormonal responses to a meal following prolonged glucose infusions have not been investigated. To determine if a 48-h glucose infusion alters hormonal responses to a test meal as well as food intake and hunger in normal weight individuals, 16 subjects (8 men, 8 women, age 18-30 years, mean BMI=21.7+/-1.6 kg/m2) were infused for 48 h with either saline (50 ml/h) or 15% glucose (200 mg/m2/min). Subjects ingested a 600 kcal mixed nutrient meal 3 h after infusion termination. Blood samples were taken during the 48 h and for 4 h following food ingestion. The 48-h glucose infusion elicited a metabolic profile of a glucose intolerant obese subjects, with increased plasma glucose, insulin and leptin (all P<0.01) and increased HOMA-IR (P<0.001). During meal ingestion, early insulin secretion was increased (P<0.05) but post-prandial glucose (P<0.01) and insulin (P<0.01) excursions were lower following the glucose infusion. Post-prandial plasma triglyceride concentrations were increased after glucose compared with saline. Food intake and hunger ratings were not different between the two conditions. Plasma leptin levels were inversely correlated with hunger (P<0.03) in both conditions and with food intake (P<0.003) during the glucose condition only. Thus, a 48-h glucose infusion does not impair post-prandial hormonal responses, alter food intake or hunger in normal weight subjects. The glucose-induced increases in plasma leptin result in a stronger inverse relationship between plasma leptin and hunger as well as food intake. These data are the first to demonstrate a relationship between leptin and hunger in normal weight, non-calorically restricted human subjects.

Prolonged (48-hour) modest hyperinsulinemia decreases nocturnal heart rate variability and attenuates the nocturnal decrease in blood pressure in lean, normotensive humans.

CONTEXT: Heart rate variability (HRV), an index of cardiac vagal activity, is decreased in individuals with metabolic disease. The relationship between decreased HRV and metabolic disease is unclear. OBJECTIVE: The objective of this study was to determine whether experimentally induced glucose intolerance decreases HRV in a circadian relevant manner in healthy individuals. DESIGN: This was a within-subject, randomized design study with subjects infused for 48 h with saline (50 ml/h) or 15% glucose (200 mg/m2.min). HRV was evaluated using time domain measurements taken over the 48-h period. Blood pressure and heart rate were monitored, and blood samples were taken. SETTING: This study was performed at the General Clinical Research Center of the Hospital of the University of Pennsylvania. PATIENTS: Sixteen healthy subjects (eight men and eight women; 18-30 yr old; mean body mass index, 21.7 +/- 1.6 kg/m2) were studied. RESULTS: After glucose infusion, mean plasma glucose was increased by 16.8% (P < 0.0001), and plasma insulin was increased by 99.4% (P < 0.0001) compared with after saline infusion. Significant decreases in homeostasis model assessment indicated a decrease in insulin sensitivity (saline, 0.52 + 0.13; glucose, 0.34 + 0.12; P < 0.0001). The nocturnal root mean square successive difference, an index of cardiac vagal activity, was significantly decreased (P < 0.01), and nocturnal HR (P < 0.001) and blood pressure were significantly elevated (saline, 107.4 +/- 2.7; glucose, 112.5 +/- 3.3 mm Hg; P < 0.05) compared with the saline control. The change in homeostasis model assessment due to glucose infusion was significantly correlated with the change in root mean square successive difference (r = 0.48; P < 0.01). CONCLUSIONS: Prolonged mild hyperinsulinemia disrupts the circadian rhythm of cardiac autonomic activity. Early changes in the neural control of cardiac activity may provide a potential mechanism mediating the pathophysiological link between impaired glucose tolerance and cardiovascular disease.