Encephalopathy and seizure activity in a COVID-19 well controlled HIV patient.

A 41-year-old male with a history of well controlled HIV presented with confusion and was found to have COVID-19. Lumbar puncture was negative. He had worsening encephalopathy with tonic-clonic seizure requiring intubation. He was treated with hydroxychloroquine and azithromycin with improvement in mental status back to baseline after 6 days.

Acute effect of running exercise on physiological Achilles tendon blood flow.

Sonographically detectable intratendinous blood flow (IBF) is found in 50%-88% of Achilles tendinopathy patients as well as in up to 35% of asymptomatic Achilles tendons (AT). Although IBF is frequently associated with tendon pathology, it may also represent a physiological regulation, for example, due to increased blood flow in response to exercise. Therefore, this study aimed to investigate the acute effects of a standardized running exercise protocol on IBF assessed with Doppler ultrasound (DU) "Advanced dynamic flow" in healthy ATs. 10 recreationally active adults (5 f, 5 m; 29±3 years, 1.72±0.12 m, 68±16 kg, physical activity 206±145 minute/wk) with no history of AT pain and inconspicious tendon structure performed 3 treadmill running tasks on separate days (M1-3) with DU examinations directly before and 5, 30, 60, and 120 minutes after exercise. At M1, an incremental exercise test was used to determine the individual anaerobic threshold (IAT). At M2 and M3, participants performed 30- minute submaximal constant load tests (CL1 /CL2 ) with an intensity 5% below IAT. IBF in each tendon was quantified by counting the number of vessels. IBF increased in five ATs from no vessels at baseline to one to four vessels solely detectable 5 minutes after CL1 or CL2 . One AT had persisting IBF (three vessels) throughout all examinations. Fourteen ATs revealed no IBF at all. Prolonged running led to a physiological, temporary appearance of IBF in 25% of asymptomatic ATs. To avoid exercise-induced IBF in clinical practice, DU examinations should be performed after 30 minutes of rest.

Is Sonographic Assessment of Intratendinous Blood Flow in Achilles Tendinopathy Patients Reliable?: Consistency of Doppler Ultrasound Modes and Intra- and Inter-observer Reliability.

PURPOSE: The purpose of this study was to investigate the consistency between different Doppler ultrasound (DU) modes as well as the intra- and inter-observer reliability of investigators with different experience level in assessing intratendinous blood flow (IBF) in Achilles tendinopathy patients. MATERIAL AND METHODS: 18 participants (36 Achilles tendons, AT) with Achilles tendinopathy (24 AT) were examined with power Doppler ultrasound (PDU), colour Doppler ultrasound (CDU) and "Advanced Dynamic Flow" (ADF) (Toshiba Xario SSA-660 A; 14MHz transducer) by 2 investigators (experienced, EI; inexperienced, II) in a test-retest design (M1/M2). A modified Öhberg score was used to quantify IBF. Data was analysed descriptively (absolute and relative). Consistency of the 3 modes was presented by Kendall's Coefficient of Concordance (Kendall's W). Intra- and inter-observer reliability were calculated by use of Kendall's tau b correlation coefficient. RESULTS: IBF was detected in 79-92% of symptomatic AT and in 33-50% of contralateral asymptomatic AT. Comparing the 3 modes, Kendall's W ranged from 0.97-0.98. Analysis of intra-observer reliability resulted in Kendall's tau 0.90-0.92 for EI and 0.84-0.87 for II. Inter-observer reliability resulted in Kendall's tau 0.64-0.69 in M1 and 0.68-0.70 in M2. CONCLUSION: The very good consistency between PDU, CDU and ADF indicates a comparable applicability for assessing IBF in ATs. Intra-observer reliability was high for both investigators, independent of experience. The moderate inter-observer reliability reflects the challenge in sonographic detection of intratendinous blood flow (IBF) amount.

The relationship of leukocyte anisocytosis to holotranscobalamin, a marker of cobalamin deficiency.

INTRODUCTION: After measurement of the mean volumes of leukocyte subpopulations as well as the distribution widths (DW) of these volumes has become available, we investigated whether such morphometric leukocyte parameters are associated with a commonly used marker of cobalamin deficiency, i.e., holotranscobalamin (HoloTC). Further, we determined reference intervals for these parameters in an elderly population. METHODS: Consecutive subjectively healthy and volunteering individuals ≥60 years were included. Using the UniCel DxH 800 Coulter Cellular Analysis System MoMV, mean neutrophil volume (NeMV), mean lymphocyte volume (LyMV), monocyte anisocytosis (MoV-DW), neutrophil anisocytosis (NeV-DW), and lymphocyte anisocytosis (LyV-DW) were assessed together with other parameters including HoloTC. RESULTS: A total of 150 individuals were included in the study. Reference intervals were not dependent on age and gender. MoV-DW (P = 0.002) and NeV-DW (P = 0.02) were significantly lower, and LyMV was significantly higher (P = 0.04) in participants with a HoloTC concentration <28 pm. In contrast, MCV, MoMV, NeMV, and LyV-DW were not associated with HoloTC concentrations. The area under the curve (AUC) in the receiver operating characteristic analysis for detecting a HoloTC <28 pm was 0.81 [95% confidence interval (CI) (0.73, 0.87)] for MoV-DW and 0.73 (0.66, 0.80) for NeV-DW. CONCLUSION: In this collective of subjectively healthy elderly individuals, monocyte anisocytosis, neutrophil anisocytosis and mean lymphocyte volume were associated with decreased HoloTC.

Diagnostic relevance of simultaneous testing for Chlamydia trachomatis and Neisseria gonorrhoeae.

BACKGROUND: The prevalence of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infection in a Swiss cohort among individuals consulting for screening or symptomatic reasons is not very well known. METHODS: Between January 2009 and January 2010, diagnostic samples referred to us to test for either CT or NG or both were simultaneously analysed for both infections. Testing was performed using the commercial m2000sp and m2000rt devices from Abbott Diagnostics involving automated DNA extraction and semi-quantitative real-time polymerase chain reaction (PCR), respectively. RESULTS: A total of 9,245 individuals (8,009 female, 1,236 male) were tested. CT alone was found in 318 (3.97%) samples from female patients and NG infections were found in 5 (0.06%) of the female samples. Six (0.08%) women had both CT and NG infections. The numbers for males were 72 (5.83%) for CT alone, 18 (1.14%) for NG alone and 8 (0.65%) for coincident infections. Among women, a selective testing approach in which only the presence of CT was investigated missed six NG cases (0.07% prevalence, 54.55% of all NG-positive women) and the request to test only for NG missed two CT cases (0.02% prevalence, 0.62% of all CT-positive women). For the male samples, one NG case (0.08% prevalence, 3.85% of all NG-positive men) was missed when only CT was requested and three CT cases (0.24% prevalence, 3.75% of all CT-positive men) were overlooked when only NG testing was requested. CONCLUSION: A sizeable number (12) of CT and NG cases is missed by physician-referred testing for only one of the two pathogens.

Metabolic and anti-inflammatory benefits of eccentric endurance exercise - a pilot study.

BACKGROUND: Eccentric endurance exercise (e.g. hiking downwards) is less strenuous than concentric exercise (e.g. hiking upwards) but its potential to reduce cardiovascular risk is unknown. MATERIALS AND METHODS: We randomly allocated 45 healthy sedentary individuals (16 men and 29 women, mean age 48 years) to one of two groups, one beginning with two months of hiking upwards, the other with two months of hiking downwards the same route, with a crossover for a further two months. For the opposite way, a cable car was used where compliance was recorded electronically. The difference in altitude was 540 metres; the distance was covered three to five times a week. Fasting and postprandial metabolic profiles were obtained at baseline and after the two month periods of eccentric and concentric exercise, respectively. RESULTS: Forty-two of the 45 participants completed the study; the compliance rate was therefore 93%. Compared with baseline, eccentric exercise lowered total cholesterol (by 4.1%; P = 0.026), low-density lipoprotein (LDL) cholesterol (by 8.4%, P = 0.001), Apolipoprotein B/Apolipoprotein A1 ratio (by 10.9%, P < 0.001), homeostasis model assessment of insulin resistance scores (by 26.2%, P = 0.017) and C-reactive protein (by 30.0%; P = 0.007); the magnitude of these changes was comparable to that of concentric exercise. Eccentric exercise improved glucose tolerance (by 6.2%, P = 0.023), whereas concentric exercise improved triglyceride tolerance (by 14.9%, P = 0.022). CONCLUSIONS: Eccentric endurance exercise is a promising new exercise modality with favourable metabolic and anti-inflammatory effects and is well applicable to sedentary individuals.

Glomerular filtration rate estimates decrease during high altitude expedition but increase with Lake Louise acute mountain sickness scores.

AIM: Acute mountain sickness (AMS) can result in pulmonary and cerebral oedema with overperfusion of microvascular beds, elevated hydrostatic capillary pressure, capillary leakage and consequent oedema as pathogenetic mechanisms. Data on changes in glomerular filtration rate (GFR) at altitudes above 5000 m are very limited. METHODS: Thirty-four healthy mountaineers, who were randomized to two acclimatization protocols, undertook an expedition on Muztagh Ata Mountain (7549 m) in China. Tests were performed at five altitudes: Zurich pre-expedition (PE, 450 m), base camp (BC, 4497 m), Camp 1 (C1, 5533 m), Camp 2 (C2, 6265 m) and Camp 3 (C3, 6865 m). Cystatin C- and creatinine-based (Mayo Clinic quadratic equation) GFR estimates (eGFR) were assessed together with Lake Louise AMS score and other tests. RESULTS: eGFR significantly decreased from PE to BC (P < 0.01). However, when analysing at changes between BC and C3, only cystatin C-based estimates indicated a significant decrease in GFR (P = 0.02). There was a linear decrease in eGFR from PE to C3, with a decrease of approx. 3.1 mL min(-1) 1.73 m(-2) per 1000 m increase in altitude. No differences between eGFR of the two groups with different acclimatization protocols could be observed. There was a significant association between eGFR and haematocrit (P = 0.01), whereas no significant association between eGFR and aldosterone, renin and brain natriuretic peptide could be observed. Finally, higher AMS scores were significantly associated with higher eGFR (P = 0.01). CONCLUSIONS: Renal function declines when ascending from low to high altitude. Cystatin C-based eGFR decreases during ascent in high altitude expedition but increases with AMS scores. For individuals with eGFR <40 mL min(-1) 1.73 m(-2), caution may be necessary when planning trips to high altitude above 4500 m above sea level.

Leptin, leptin soluble receptor and coronary atherosclerosis.

BACKGROUND: The adipose tissue-related hormone leptin plays an important role in the regulation of body weight. The associations of leptin and leptin soluble receptor (sOb-R) with coronary artery disease (CAD) are not clear. DESIGN: We measured leptin and sOb-R in 543 consecutive patients (379 men, 164 women) referred for coronary angiography for the evaluation of CAD. Coronary artery stenoses with lumen narrowing > or = 50% were considered significant. RESULTS: Serum leptin correlated significantly with body mass index (r(s) = 0.443), with insulin resistance as assessed by the homeostasis model for the assessment of insulin resistance (r(s) = 0.339), with serum triglycerides (r(s) = 0.181), with systolic as well as diastolic blood pressure (r(s) = 0.170 and r(s) = 0.133, respectively) and, inversely, with sOb-R (r(s) = -0.346; P < 0.01 for all correlations). Coronary angiography revealed significant coronary artery stenoses in 331 (61%) of our patients. Serum leptin was significantly lower in patients with significant coronary artery stenoses than in patients without such lesions (8.5 +/- 7.8 vs. 13.2 +/- 12.2 ng mL(-1); P < 0.001). Multivariate logistic regression analysis proved serum leptin inversely and independently associated with the presence of significant coronary artery stenoses (standardized adjusted odds ratio 0.746, 95% confidence interval 0.566-0.983, P = 0.038). In contrast to serum concentrations of leptin, serum concentrations of sOb-R did not significantly differ between patients with significant stenoses and those without such lesions (22.4 +/- 8.3 vs. 23.1 +/- 12.1 ng mL(-1); P = 0.655). CONCLUSIONS: Serum leptin but not sOb-R is significantly lower in patients with angiographically determined CAD. Despite its association with cardiovascular risk factors, leptin should not be simply regarded as a promoter of atherosclerosis.

[Hemoglobinopathies--clinical symptoms and diagnosis of thalassemia and abnormal hemoglobins]. / Hämoglobinopathien--Klinik und Diagnostik von Thalassämien und anomalen Hämoglobinen.

Haemoglobinopathies constitute entities that are generated by either an abnormal haemoglobin or thalassaemias. While abnormal haemoglobins are caused by a qualitative structural abnormality of the haemoglobin molecule, thalassaemias result by diminished synthesis of the globin chain. Due to increased immigration from Asia, Africa and the Mediterranean to Northern Europe, haemoglobin S, haemoglobin C, haemoglobin E are also encountered commonly in Switzerland, while other abnormal haemoglobins are rare, yet can cause clinically relevant symptoms. This include haemolysis, polyglobulia, cyanosis or a combination thereof Thalassaemia-syndroms constitute with two million affected individuals to the most prelevant monogenetic diseases worldwide. Due to migration into Switzerland, they are also found quite commonly among our patients with 10-15 per cent of all hypochromic, microcytic, anemia second only to iron deficiency. Importantly, thalassaemias and haemoglobinopathies can occur concomitantly sometimes even with a normal haemoglobin variant. This results in wide-spread presentations, making diagnosis and clinical judgement difficult. We describe in this article not only physiological mechanisms and clinical presentation but also propose a step-wise diagnostic algorithm including selective use of molecular biology methods.

[Conventional and new laboratory parameters in the evaluation of hematologic disease]. / Neue und alte Parameter in der Diagnostik von hämatologischen Erkrankungen.

Laboratory investigation plays a crucial role in the workup of hematological disease. The well established method of morphological analysis of blood components has been continuously complemented by other methods. On one hand, these consist of considerable improvements of methods employed for automated cell enumeration allowing for early and accurate detection of cell subpopulations, and quantification of valuable red cell parameters, which are of use in the differential diagnosis of anemia. On the other hand, several parameters for the differentiation of microcytic anemia have become available often allowing for the sometimes difficult diagnosis of anemia of chronic disease, iron deficiency anemia, or thalassemia (ferritin, soluble transferrin receptor, transferrin saturation, RDW, zinc protoporphyrin, as well as reticulocyte indices CHr, Ret-Y Hypo%). In macrocytic anemia, introduction of methods to measure methylmalonic acid (MMA), homocystein, holotranscobalamin (holo-TC), complement the determinations of vitamin concentrations (vitamin B12, folic acid in serum and erythrocytes). Employing these newer parameters in addition to the well established ones allows for detection of early or combined disease. The clinician has to know the diagnostic characteristics not only of the old but also of the newer parameters.

[Differential diagnosis of anemia]. / Differentialdiagnose der Anämien.

Anemia is often encountered in clinical practice. It has to be noted that anemia is only a symptom of an underlying disease. Early, correct and consequent diagnosis is crucial in order to prevent late detection of fatal disease or to prescribe contraindicated therapy. The combined use of a morphologic and physiologic classification allows for understanding and correct classification of anemia in a specific patient. In this respect, the determination of reticulocyte counts is of special importance. Further targeted biochemical, morphological and immunological analysis leads to the definitive diagnosis of anemia. A large proportion of the anemias can be diagnosed and treated by the general practitioner. However, involvement of a haematologist is recommended in several clinical situations, such as newly diagnosed haemolytic anemia, as well as in patients with complex, equivocal or therapy-refractory anemia or certain normocytic hyporegenerative anemias. This paper presents a differentiated stepwise approach in diagnosing anemic disorders.

Assessment of renal function in renal transplant patients using cystatin C. A comparison to other renal function markers and estimates.

To date, little evidence is available to define the role of cystatin C in patients with renal transplants. Thus, to assess, whether cystatin C (CysC) provides better information on renal function than other markers, CysC, creatinine clearance (CrCl), serum creatinine (SCr), beta2-microglobulin (beta2-M), and 125I-Iothalamate clearance were determined in 30 patients. Correlation and ROC curves were obtained and characteristics like sensitivity and specificity were calculated. Further, to evaluate the usefulness of these markers for monitoring, intraindividual coefficients of variation for CysC and SCr measurements were compared in 85 renal transplant patients. CysC correlated best with GFR, whereas SCr, CrCl and beta2-M all had lower correlation coefficients. CysC was superior to SCr, even when renal function equations of were used. The diagnostic accuracy of CysC was significantly better than SCr. but did not differ significantly from CrCl and beta2-M. Together, our data show that in patients with renal transplants, CysC has a similar diagnostic value as CrCl. However, it is superior to determinations of SCr. The intraindividual variation of CysC is significantly greater than that of SCr. This might be due to better ability of CysC to reflect temporary changes especially in mildly impaired GFR, most critical for early detection of rejection and other function impairment. In conclusion, CysC allows for easy and accurate assessment of renal function (GFR) in steady state renal transplant patients and is clearly superior to the commonly used serum creatinine.

Urine analysis performed by flow cytometry: reference range determination and comparison to morphological findings, dipstick chemistry and bacterial culture results--a multicenter study.

AIM: To validate whether quantitative flow-cytometric analysis of particulate matter in urine would allow for accurate and rapid enumeration of red blood cells (RBC), leukocytes (WBC), squamous epithelial cells (EC), casts, and bacteria, a Sysmex UF-100 analyzer was tested in a multicenter study. MATERIAL AND METHODS: At first, reference values were established and found to be < 14 for RBC, < 16 for WBC, < 9 for EC, < 2 for casts and < 173 for bacteria, respectively (counts per microl; 97.5 percentile). Due to the wide use of dipstick and microscopic sediment analysis in routine urine diagnostics, comparative studies on 950 random urine samples were performed. Bacterial counting combined with WBC enumeration was further compared in 266 routine urinary microbiologic cultures. RESULTS: Good correlations were found comparing UF-100 results of RBC (r = 0.89), WBC (r = 0.94), and EC (r = 0.74) with Fuchs-Rosenthal Chamber (FRC) counts. However, some misclassification of casts (r = 0.32) could be observed. Correlations of UF-100 with dipstick and sediment testing was significant (p < 0.001), but the scatter of the latter two methods is too wide to consider them as quantitative methods. Promising results further revealed that the analyzer has a good negative predictive value (NPV) for microbiologically negative cultures, especially for cultures with bacterial counts of 10(5)/l (NPV = 95%). CONCLUSION: The analyzer is capable of providing rapid and reliable urine analysis of cellular particles avoiding the known imprecision of dipstick and sediment methodology. Thus, when used in an algorithm, combined with dipstick or quantitative urine chemistry analysis (for hemoglobin, esterase, protein, glucose, etc.), this analyzer might serve as a rapid and accurate screening tool in routine urine analysis, thereby reducing manual reviewing rate as well as the number of missed samples, compared to screening with dipstick alone.

ET gets HIT--thrombocytotic heparin-induced thrombocytopenia (HIT) in a patient with essential thrombocythemia (ET).

Immune-mediated heparin-induced thrombocytopenia (HIT) is a relatively common complication in patients receiving heparin, and represents a strong risk factor for thromboembolic disease associated with high morbidity and mortality. The condition is commonly defined as a platelet count fall of greater than 30-50% to values below 150 x 10(9)/l. Despite this, several cases with platelet count nadirs in the normal range have been reported. This report describes a patient with status post-carotid thrombendarterectomy presenting with neurological symptoms and thrombocytosis (1235 x 10(9)/l), which in due course was diagnosed to be caused by essential thrombocythemia (ET). Heparin therapy was established and symptoms resolved markedly. After 5 days of standard heparin therapy, serologically confirmed HIT with new neurological symptoms occurred. The platelet count nadir attributed to HIT was far above normal (633 x 10(9)/l), which nevertheless represented a substantial relative platelet count fall (49%). This is the first reported case of serologically confirmed HIT in a patient with ET. Furthermore, it represents the first published case of HIT being present in thrombocytosis. Clinicians should be aware that atypical HIT can even be present in thrombocytosis and, because of nomenclature, HIT with normal and elevated platelet count nadirs is likely to be largely underdiagnosed.

Rapid and accurate assessment of glomerular filtration rate in patients with renal transplants using serum cystatin C.

BACKGROUND: Assessment of renal function in patients with renal transplants is of great importance. Various studies have reported cystatin C as an easily and rapidly assessable marker that can be used for accurate information on renal function impairment. To date, no study is available to define the role of cystatin C in patients with renal transplants. METHODS: Thirty steady-state patients (50% male/50% female) with status post-kidney transplantation were studied. To assess renal function, cystatin C, creatinine clearance, serum creatinine, beta2-microglobulin (beta2M), and [125I]iothalamate clearance were determined. Correlations and non-parametric ROC curves for accuracy, using a cut-off glomerular filtration rate (GFR) of 60 ml/min, were obtained for the different markers allowing for calculations of positive predictive values (PPV), positive likelihood ratios (PLR), specificity and sensitivity, respectively. Further, to evaluate the usefulness of these markers for monitoring, intraindividual coefficients of variation (CVs) for cystatin C and creatinine measurements were compared in 85 renal transplant patients. Measurements consisted of at least six pairs of results, which were obtained at different time points during routine follow-up. RESULTS: Cystatin C correlated best with GFR (r=0.83), whereas serum creatinine (r=0.67), creatinine clearance (r=0.57) and beta2M (r=0.58) all had lower correlation coefficients. The diagnostic accuracy of cystatin C was significantly better than serum creatinine (P=0.025), but did not differ significantly from creatinine clearance (P=0.76) and beta2M (P=0.43). At a cut-off of 1.64 mg/l, cystatin C has a PPV of 93%, PLR of 6.4, specificity 89% and sensitivity 70%, respectively. For beta2M, PPV 83%, PLR 1.7, specificity 67% and sensitivity 75% was seen at a cut-off of 3.57 mg/l. Accordingly, at a cut-off of 125 micromol/l for serum creatinine, a PPV 76%, PLR 1.4, specificity 44% and sensitivity 80% was revealed. Finally, at a cut-off of 66 ml/min/1.73 m2 for creatinine clearance, the following characteristics were found: PPV 94%, PLR 7.7, specificity 89% and sensitivity 85%. The intraindividual variation of creatinine was significantly lower than that of cystatin C (P<0.001). With increasing concentrations, their ratios of CV tended towards a value of 1, demonstrating identical variability at low GFR. CONCLUSION: Together, our data show that in patients with renal transplants, cystatin C, in terms of PPV and PLR, has a similar diagnostic value as creatinine clearance. However, it is superior to serum determinations of creatinine and beta2M. The intraindividual variation of cystatin C is greater than that of creatinine. This might be due to the better ability of cystatin C to reflect temporary changes especially in mildly impaired GFR, most critical for early detection of rejection and other function impairment. Thus, cystatin C allows for rapid and accurate assessment of renal function (GFR) in renal transplants and is clearly superior to the commonly used serum creatinine.