Intracerebral endotheliitis and microbleeds are neuropathological features of COVID-19.

Coronavirus disease 19 (COVID-19) is a rapidly evolving pandemic caused by the coronavirus Sars-CoV-2. Clinically manifest central nervous system symptoms have been described in COVID-19 patients and could be the consequence of commonly associated vascular pathology, but the detailed neuropathological sequelae remain largely unknown. A total of six cases, all positive for Sars-CoV-2, showed evidence of cerebral petechial hemorrhages and microthrombi at autopsy. Two out of six patients showed an elevated risk for disseminated intravascular coagulopathy according to current criteria and were excluded from further analysis. In the remaining four patients, the hemorrhages were most prominent at the grey and white matter junction of the neocortex, but were also found in the brainstem, deep grey matter structures and cerebellum. Two patients showed vascular intramural inflammatory infiltrates, consistent with Sars-CoV-2-associated endotheliitis, which was associated by elevated levels of the Sars-CoV-2 receptor ACE2 in the brain vasculature. Distribution and morphology of patchy brain microbleeds was clearly distinct from hypertension-related hemorrhage, critical illness-associated microbleeds and cerebral amyloid angiopathy, which was ruled out by immunohistochemistry. Cerebral microhemorrhages in COVID-19 patients could be a consequence of Sars- CoV-2-induced endotheliitis and more general vasculopathic changes and may correlate with an increased risk of vascular encephalopathy.

Prevention of Adrenal Crisis: Cortisol Responses to Major Stress Compared to Stress Dose Hydrocortisone Delivery.

CONTEXT: Patients with adrenal insufficiency require increased hydrocortisone cover during major stress to avoid a life-threatening adrenal crisis. However, current treatment recommendations are not evidence-based. OBJECTIVE: To identify the most appropriate mode of hydrocortisone delivery in patients with adrenal insufficiency who are exposed to major stress. DESIGN AND PARTICIPANTS: Cross-sectional study: 122 unstressed healthy subjects and 288 subjects exposed to different stressors (major trauma [N = 83], sepsis [N = 100], and combat stress [N = 105]). Longitudinal study: 22 patients with preserved adrenal function undergoing elective surgery. Pharmacokinetic study: 10 patients with primary adrenal insufficiency undergoing administration of 200 mg hydrocortisone over 24 hours in 4 different delivery modes (continuous intravenous infusion; 6-hourly oral, intramuscular or intravenous bolus administration). MAIN OUTCOME MEASURE: We measured total serum cortisol and cortisone, free serum cortisol, and urinary glucocorticoid metabolite excretion by mass spectrometry. Linear pharmacokinetic modeling was used to determine the most appropriate mode and dose of hydrocortisone administration in patients with adrenal insufficiency exposed to major stress. RESULTS: Serum cortisol was increased in all stress conditions, with the highest values observed in surgery and sepsis. Continuous intravenous hydrocortisone was the only administration mode persistently achieving median cortisol concentrations in the range observed during major stress. Linear pharmacokinetic modeling identified continuous intravenous infusion of 200 mg hydrocortisone over 24 hours, preceded by an initial bolus of 50-100 mg hydrocortisone, as best suited for maintaining cortisol concentrations in the required range. CONCLUSIONS: Continuous intravenous hydrocortisone infusion should be favored over intermittent bolus administration in the prevention and treatment of adrenal crisis during major stress.

Twenty-four-hour ambulatory blood pressure monitoring in very elderly patients: Comparison of in-hospital versus home follow-up results.

Elevated blood pressure (BP) is frequently diagnosed in very elderly hospitalized patients. Accurate diagnosis of hypertension is challenging in the hospital environment, due to the "white coat effect," and both overtreatment and undertreatment can adversely affect clinical outcome. Twenty-four-hour ambulatory blood pressure monitoring (ABPM) has the potential to avoid the "white coat effect" and accurately guide the management of hypertension. However, effects of the hospital environment on ABPM are unknown in the very elderly. We set out to enroll 45 patients, age ≥70 years, with elevated conventional BP during hospitalization in this observational study. It was prespecified by protocol to assess initially the difference between 24-hour BP during hospital-admission and home follow-up. Subsequent analysis should investigate the change in anxiety (Hospital Anxiety and Depression Scale-A [HADS-A]) after discharge, the correlation with change in 24-hour BP after discharge, and the prevalence of orthostatic hypertension. Thirty-one patients were included in the final analysis (age 83.5 ±â€Š4.4 years; 71% female). Twenty-four-hour BP decreased significantly after hospital discharge (systolic from 133.5 ±â€Š15.6 to 126.2 ±â€Š14.4 mm Hg [millimeter of mercury], P = .008; diastolic from 71.0 ±â€Š9.0 to 68.3 ±â€Š8.6 mm Hg, P = .046). Anxiety level (HADS-A) decreased significantly after discharge, from 7.5 (interquartile range [IQR]: 4.0-13.8) to 5.0 (IQR: 4.0-8.0, P = .012). The change in anxiety was a predictor of change in systolic BP after discharge (F[1,20] = 5.9, P = .025). Sixty-one percent of the patients had significant orthostatic hypotension during hospital stay. In conclusion, 24-hour BP in very elderly patients is lower in the home environment than during hospitalization. This phenomenon seems to be directly linked to a lower anxiety-level at home. Reassessing hypertension at home may decrease the need for (intensified) antihypertensive medical therapy in a substantial number of patients. This is particularly important in the very elderly, who have a high prevalence of symptomatic and asymptomatic orthostatic hypotension, making them prone to hazardous effects of antihypertensive therapy.

An unusual cause of febrile hepatitis.

We describe the case of a 51-year-old man with recently diagnosed ulcerative colitis who developed fever and elevated liver enzymes as well as cholestasis a few weeks after starting treatment with mesalazine. As no obvious cause was found and fever persisted, liver biopsy was performed and revealed granulomatous hepatitis. The patient recovered completely after cessation of mesalazine, so that a drug-induced granulomatous hepatitis after exclusion of other differential diagnoses in an extensive work up was assumed. The present case demonstrates that even though drug-induced liver injury due to mesalazine is rare, it should be considered in unclear cases and lead to prompt discontinuation of mesalazine.

An unusual cure for acromegaly.

The authors present the case of a 30-year-old female patient with acromegaly whose disease had not been cured after transcranial neurosurgery, two transsphenoidal surgeries and stereotactic radiosurgery. She required treatment with octreotide and pegvisomant to normalise growth hormone levels. Seven years after the diagnosis of acromegaly, she noticed acute vision loss in her left eye and presented with meningism. She had an intrasellar abscess which was confirmed and treated by surgical drainage. As a result of the abscess, she was cured of acromegaly and able to discontinue both octreotide and pegvisomant.

The German version of the Assessment of Chronic Illness Care: instrument translation and cultural adaptation.

BACKGROUND: In Switzerland, there is a dearth of information on the extent to which patients with chronic illnesses receive care congruent with the Chronic Care Model (CCM). To drive quality improvement programmes, it is necessary to have practical assessment tools in the country's own language to evaluate the delivery of CCM activities. METHODS: German translation and adaptation of the original Assessment of Chronic Illness Care (ACIC). We followed a sequential forward and backward translation approach. In a multidisciplinary committee review the original English version and the translations were compared, instructions and formats modified and cross-cultural equivalences verified. The second version was pre-tested and multidisciplinary group discussion led to the final version which aimed to create a comprehensive culturally adapted translation capturing the original idea of the items rather than a direct one to one translation. RESULTS: Difficulties encountered during the translation process consisted in the difference of health care settings and health care organization in Switzerland and USA.The adapted German version was delivered to a managed care organization in the city of Zurich to test the initial use for diabetes care. The average ACIC subscale scores were: organization of the health care delivery system: mean (m) = 7.31 (SD = 0.79), community linkages: m = 3.78 (SD = 1.09), self-management support: m = 4.88 (SD = 1.21), decision support: m = 4.79 (SD = 1.16), delivery system design: m = 5.56 (SD = 1.28) and clinical information systems: m = 4.50 (SD = 2.69). Overall, the ACIC subscale scores were comparable with the scores of the original testing. CONCLUSION: After cultural adaptations the German version of the ACIC is applicable as a tool to guide quality improvement in chronic illness care in German speaking countries in Europe.

Low to moderate sugar-sweetened beverage consumption impairs glucose and lipid metabolism and promotes inflammation in healthy young men: a randomized controlled trial.

BACKGROUND: Sugar-sweetened beverages (SSBs) have unfavorable effects on glucose and lipid metabolism if consumed in high quantities by obese subjects, but the effect of lower doses in normal-weight subjects is less clear. OBJECTIVE: The aim was to investigate the effects of SSBs consumed in small to moderate quantities for 3 wk on LDL particle distribution and on other parameters of glucose and lipid metabolism as well as on inflammatory markers in healthy young men. DESIGN: Twenty-nine subjects were studied in a prospective, randomized, controlled crossover trial. Six 3-wk interventions were assigned in random order as follows: 600 mL SSBs containing 1)40 g fructose/d [medium fructose (MF)], 2) 80 g fructose/d [high fructose (HF)], 3) 40 g glucose/d [medium glucose (MG)], 4) 80 g glucose/d [high glucose (HG)], 5) 80 g sucrose/d [high sucrose (HS)], or 6) dietary advice to consume low amounts of fructose. Outcome parameters were measured at baseline and after each intervention. RESULTS: LDL particle size was reduced after HF by -0.51 nm (95% CI: -0.19, -0.82 nm) and after HS by -0.43 nm (95% CI: -0.12, -0.74; P < 0.05 for both). Similarly, a more atherogenic LDL subclass distribution was seen when fructose-containing SSBs were consumed (MF, HF, and HS: P < 0.05). Fasting glucose and high-sensitivity C-reactive protein (hs-CRP) increased significantly after all interventions (by 4-9% and 60-109%, respectively; P < 0.05); leptin increased during interventions with SSBs containing glucose only (MG and HG: P < 0.05). CONCLUSION: The present data show potentially harmful effects of low to moderate consumption of SSBs on markers of cardiovascular risk such as LDL particles, fasting glucose, and hs-CRP within just 3 wk in healthy young men, which is of particular significance for young consumers. This trial was registered at clinicaltrials.gov as NCT01021969.

Paraneoplastic hyperthyroidism.

The authors describe a 31-year-old male with a metastatic germ cell tumour and massively elevated human chorionic gonadotrophin (HCG) levels who presented with hyperthyroidism. As HCG is structurally closely related to thyroid stimulating hormone (TSH), it can activate the TSH receptor; grossly elevated levels may result in hyperthyroidism. After initiation of chemotherapy, HCG levels decreased and hyperthyroidism resolved.

Assessment of Chronic Illness Care with the German version of the ACIC in different primary care settings in Switzerland.

BACKGROUND: In Switzerland the extent to which patients with chronic illnesses receive care congruent with the Chronic Care Model (CCM) is unknown. METHODS: According to guidelines we translated the Assessment of Chronic Illness Care (ACIC) into German (G-ACIC). We tested the instrument in different primary care settings and compared subscales with the original testing. RESULTS: Difficulties encountered during the translation process consisted in the difference of health care settings in Switzerland and USA. However initial testing showed the G-ACIC to be a suitable instrument. The average ACIC subscale scores in Swiss managed care (MC)-, group (GP)- and single handed practices (SP) were higher for MC practices than for group- and single handed practices: Organization of the healthcare delivery system: MC mean (m) = 6.80 (SD 1.55), GP m = 5.42 (SD 0.99), SP m = 4.60 (SD 2.07); community linkages: MC m = 4.19 (SD 1.47), GP m = 4.83 (SD 1.81), SP m = 3.10 (SD 2.12); self-management support: MC m = 4.96 (SD 1.13), GP m = 4.73 (SD 1.40), SP m = 4.43 (SD 1.34); decision support: MC m = 4.75 (SD 1.06); GP m = 4.20 (SD 0.87), SP m = 3.25 (SD 1.59); delivery system design: MC m = 5.98 (SD 1.61), GP m = 5.05 (SD 2.05), SP m = 3.86 (SD 1.51) and clinical information systems: MC m = 4.34 (SD = 2.49), GP m = 2.06 (SD 1.35), SP m = 3.20 (SD 1.57). CONCLUSIONS: The G-ACIC is applicable and useful for comparing different health care settings in German speaking countries. Managed care organizations seem to implement the different components of the CCM in a greater extend than group and single handed practices. However, much room exists for further improvement.

Minimally invasive application of botulinum toxin A in patients with idiopathic rhinitis.

BACKGROUND: Nasal hypersecretion due to idiopathic rhinitis can often not be treated sufficiently by conventional medication. Botulinum toxin A (BTA) has been injected into the nasal mucosa in patients with nasal hypersecretion with a reduction of rhinorrhea lasting for about 4 to 8 weeks. Since the nasal mucosa is well supplied with glands and vessels, the aim of this study was to find out if the distribution of BTA in the nasal mucosa and a reduction of nasal hypersecretion can also be reached by a minimally invasive application by sponges without an injection. METHODS: Patients were randomly divided into two groups. The effect of BTA (group A, C, D) or saline as placebo (group B) was investigated in 20 patients with idiopathic rhinitis by applying it with a sponge soaked with BTA (40 units each nostril) or saline. Subgroups C and D contained these patients of group A and B who did not improve in symptoms one week after the original treatment (either BTA or saline) who then received the alternative medication. Changes of symptoms (rhinorrhea, nasal obstruction) were scored by the patients in a four point scale and counted (consumption of tissues, sneezing) in a diary. The patients were followed up weeks 1, 2, 4, 8 and 12. RESULTS: There was a clear reduction of the amount of secretion in group A compared to group B, C and D. This did not correlate with the tissue consumption, which was comparably reduced in group A and B, but reduced less in group C and D. Sneezing was clearly reduced in group A but comparably unchanged in group B and C and increased in group D. Nasal congestion remained unchanged. CONCLUSION: In some patients with therapy-resistant idiopathic rhinitis BTA applied with a sponge is a long-lasting and minimal invasive therapy to reduce nasal hypersecretion.