Low-level HIV viraemia during antiretroviral therapy: Longitudinal patterns and predictors of viral suppression.

OBJECTIVES: Our objective was to characterize longitudinal patterns of viraemia and factors associated with viral suppression in people with HIV and low-level viraemia (LLV) during antiretroviral therapy (ART). METHODS: We included people with HIV in the EuResist Integrated Database with LLV following ART initiation after 2005. LLV was defined as two or more consecutive viral load (VL) measurements of 51-199 copies/mL 30-365 days apart after >12 months of ART. Viraemia patterns were analyzed over 24 months. Factors associated with viral suppression at 12 months after LLV episodes were identified using univariable and multivariable logistic regression. RESULTS: Of 25 113 people with HIV, 2474 (9.9%) had LLV. Among 1387 participants with 24 months of follow-up after LLV, 406 (29%) had persistent suppression, 669 (48%) had transient viraemic episodes, 29 (2%) had persistent LLV, and 283 (20%) had virological failure. Following LLV episodes, the proportion with detectable viraemia declined (p for trend <0.001 and 0.034, in the first and second year, respectively). At 12 months, 68% had undetectable VL, which was associated with suppression before LLV (adjusted odds ratio [aOR] 1.7; 95% confidence interval [CI] 1.2-2.4) and ART modification after LLV (aOR 1.6; 95% CI 1.0-2.4). The following factors were negatively associated with undetectable VL at 12 months: higher VL during LLV (aOR 0.57 per log10 copies/mL; 95% CI 0.37-0.89), injecting drug use (aOR 0.67; 95% CI 0.47-0.96), and regimens with protease inhibitors (aOR 0.65; 95% CI 0.49-0.87) or combined anchor drugs (aOR 0.52; 95% CI 0.32-0.85). CONCLUSION: Most people with LLV did not experience sustained viral suppression during 24-month follow-up, supporting the association between LLV and inferior treatment outcome.

[Career prospects for ophthalmologists under 49 years old : A survey in Germany from 2022]. / Berufliche Zukunftsperspektive von Augenärzten unter 49 Jahren : Eine Umfrage in Deutschland aus dem Jahr 2022.

OBJECTIVE: The need for care in ophthalmology is constantly increasing due to demographic changes. The study analyzed the current professional situation and future prospects of ophthalmologists under 49 years old. METHODS: The survey of members of the German Association of Ophthalmologists (Berufsverband der Augenärzte Deutschlands) and the German Ophthalmologic Society (Deutsche Ophthalmologische Gesellschaft) was conducted in 2022. All members under the age of 49 years received an online questionnaire on the current professional situation as well as future perspectives (desired working hours, form of organization). The results of the survey were additionally compared with the 2016 survey of the German Association of Ophthalmologists. A similar questionnaire was used at that time. RESULTS: A total of 1014 people participated in the survey (62.7% women, mean age 39.3 ± 8 years, 75.6% specialists). The response rate to the survey was 25%. Specialist practice from 0 to 5 years showed a higher number of employed ophthalmologists (21% self-employed vs. 32% employed); over time the number of self-employed ophthalmologists increased (6-10 years: 40%, > 10 years: 59.3%). Overall, 46% of women were employed in a practice compared with 33% of men. Of the self-employed specialists, 95.9% said they planned to work in the same type of employment in 10 years as currently. Regarding ophthalmologists' career future, the other employment types showed a desire to move to independent practice. Compared to the 2016 survey, gender differences related to the current type of employment were evident. The number of self-employed women decreased from 43% to 26% and self-employed men decreased from 63% to 39%. The number of ophthalmologists in ambulatory healthcare centers was doubled compared to 2016. Ophthalmologists reported similar future perspectives at both survey times. CONCLUSION: The results of the survey of ophthalmologists under 49 years in Germany showed similar perceptions as in 2016. It became clear that the desire to be self-employed in 10 years is very high; however, ophthalmologists expected large practices or medical care centers to prevail in the market. The number of self-employed doctors is decreasing and the desire for self-employment is difficult to realize.

Predictors and outcomes in primary depression care (POKAL) - a research training group develops an innovative approach to collaborative care.

BACKGROUND: The interdisciplinary research training group (POKAL) aims to improve care for patients with depression and multimorbidity in primary care. POKAL includes nine projects within the framework of the Chronic Care Model (CCM). In addition, POKAL will train young (mental) health professionals in research competences within primary care settings. POKAL will address specific challenges in diagnosis (reliability of diagnosis, ignoring suicidal risks), in treatment (insufficient patient involvement, highly fragmented care and inappropriate long-time anti-depressive medication) and in implementation of innovations (insufficient guideline adherence, use of irrelevant patient outcomes, ignoring relevant context factors) in primary depression care. METHODS: In 2021 POKAL started with a first group of 16 trainees in general practice (GPs), pharmacy, psychology, public health, informatics, etc. The program is scheduled for at least 6 years, so a second group of trainees starting in 2024 will also have three years of research-time. Experienced principal investigators (PIs) supervise all trainees in their specific projects. All projects refer to the CCM and focus on the diagnostic, therapeutic, and implementation challenges. RESULTS: The first cohort of the POKAL research training group will develop and test new depression-specific diagnostics (hermeneutical strategies, predicting models, screening for suicidal ideation), treatment (primary-care based psycho-education, modulating factors in depression monitoring, strategies of de-prescribing) and implementation in primary care (guideline implementation, use of patient-assessed data, identification of relevant context factors). Based on those results the second cohort of trainees and their PIs will run two major trials to proof innovations in primary care-based a) diagnostics and b) treatment for depression. CONCLUSION: The research and training programme POKAL aims to provide appropriate approaches for depression diagnosis and treatment in primary care.

Resolution of feline Mycobacterium panniculitis despite protracted treatment with methylprednisolone acetate.

Saprophytic or non-tuberculous mycobacteria are ubiquitous in the environment. They can cause opportunistic infections when the skin is broken and typically manifest with draining sinus tracts or cutaneous nodules. This report details the first confirmed Mycobacterium smegmatis panniculitis in a cat in South Africa. Despite repeated treatment with methylprednisolone acetate for six months prior to diagnosis, the cat made an uneventful recovery once switched to doxycycline and marbofloxacin.

Successful treatment of a South African cat with effusive feline infectious peritonitis with remdesivir.

Historically, feline infectious peritonitis (FIP) has been considered almost invariably fatal. The recent COVID-19 pandemic has fuelled research in coronavirus pathophysiology and treatment. An unintended consequence is that we now have an effective treatment accessible for FIP. This paper reports on the successful resolution of immunohistochemistry-confirmed effusive FIP in an adolescent cat in South Africa following monotherapy with remdesivir at 4.9-5.6 mg/kg daily for 80 days.

Topological magnon band structure of emergent Landau levels in a skyrmion lattice.

The motion of a spin excitation across topologically nontrivial magnetic order exhibits a deflection that is analogous to the effect of the Lorentz force on an electrically charged particle in an orbital magnetic field. We used polarized inelastic neutron scattering to investigate the propagation of magnons (i.e., bosonic collective spin excitations) in a lattice of skyrmion tubes in manganese silicide. For wave vectors perpendicular to the skyrmion tubes, the magnon spectra are consistent with the formation of finely spaced emergent Landau levels that are characteristic of the fictitious magnetic field used to account for the nontrivial topological winding of the skyrmion lattice. This provides evidence of a topological magnon band structure in reciprocal space, which is borne out of the nontrivial real-space topology of a magnetic order.

[Neuroendorine paraneoplastic syndromes]. / Neuroendokrine paraneoplastische Syndrome.

Skin is commonly affected by neuroendorine paraneoplastic syndromes (PNS). This is due to the expression of receptors in the skin by which abnormally secreted neuroendocrine hormones and mediators elicit directly, and indirectly, cutaneous key signs and thus facilitate early diagnosis of these diseases. In acromegaly, induction of the growth hormone-insulin-like growth factor­1 axis results in trophic changes of the acral portions of the skin and mucosal membranes including cutis verticis gyrata. The skin signs of non-iatrogenic Cushing syndrome are identical with those of exogenous prolonged intake of glucocorticoids: centripetal accumulation of adipose tissue, plethora and striae distensae. Episodic flushing of the face and trunk (together with explosive diarrhea) is a key feature of carcinoid tumors. Fibrotic remodeling of the heart and retroperitoneal space, and less commonly of the skin, are important complications mediated by abnormally secreted 5­hydroxytryptamine (serotonin, 5­HT), the latter eliciting profibrotic responses on HT2B-receptor-expressing fibroblasts. Androgen-secreting tumors lead to well-established receptor-mediated cutaneous signs of peripheral hyperandrogenisms: seborrhea, acne, hirsutism, and androgenetic alopecia. In contrast, the pathogenesis of necrolytic migratory erythema as a key feature of glucagonoma remains incompletely understood and is thought to be related to hypoaminoacidemia. This review summarizes the clinical features of neuroendocrine PNS with skin involvement, elucidates its underlying pathophysiology, lists differential diagnoses, and explains key diagnostic steps and principal therapeutic options. An interdisciplinary approach is essential to provide the best care of all patients with neuroendocrine PNS.

Torque Teno Virus plasma level as novel biomarker of retained immunocompetence in HIV-infected patients.

PURPOSE: To predict the course of immune recovery (IR) in HIV-1-infected patients after initiation of combined antiretroviral therapy (cART) by determination of the plasma concentration of Torque Teno Virus (TTV). TTV has been identified as marker for risk assessment in immunosuppressed patients after transplantation procedures. Here, TTV was analyzed in HIV-1-infected therapy-naïve patients to evaluate its use as predictor of the course of IR for guidance of individualized treatment. METHODS: TTV DNA was quantified in plasma samples of 301 therapy-naïve HIV-1-infected patients and correlated to CD4+ cell count, HIV viral load, presence of the herpes viruses CMV, EBV and HHV-8, age and sex. Patients were classified according to their initial CD4+ cell count and to the extent of CD4+ T-cell increase within the first year of cART. RESULTS: TTV DNA was detectable in 96% of the patients' plasma samples with a median TTV plasma concentration of 5.37 log10 cop/ml. The baseline CD4+ cell count was negatively correlated with TTV plasma concentration (p = 0.003). In patients with a CD4+ cell recovery < 50 cells/µl, the median TTV plasma concentration was significantly higher compared to patients with a CD4+ cell recovery of > 200 CD4+ cells/µl (5.68 log10 cop/ml versus 4.99 log10 cop/ml; p = 0.011). TTV plasma concentration in combination with baseline CD4+ cell count were significantly correlated to CD4+ cell recovery (p = 0.004). For all other parameters considered, no significant correlation for CD4+ cell recovery was found. CONCLUSION: Within the cohort, the significantly elevated TTV plasma concentration in patients with diminished CD4+ cell recovery indicates a more profound immune defect. Baseline TTV plasma concentrations and CD4+ cell count are predictive for the course of immune recovery in HIV-1-infected patients with severe immunodeficiency.

[Cognitive dysfunction in heart failure-Causes and sequelae]. / Kognitive Dysfunktion bei Herzinsuffizienz ­ Ursachen und Folgen.

Approximately 40% of patients with heart failure show cognitive deficits, such as concentration difficulties, attention deficits, and memory impairment. Affected patients have a higher rate of rehospitalization and an increased mortality. This could be due to low adherence mediated by a lack of disease-specific knowledge and strategies to deal with symptom exacerbation. The pathogenesis of cognitive deficits in heart failure is multifactorial. In this respect the heart failure itself as well as cardiovascular risk factors and comorbidities play a role. Orientating neuropsychological screening tests can show a first indication of the presence of cognitive impairment. When identified, the causes can be specifically treated and care can be optimized through certain measures, such as the involvement of caregivers and healthcare providers.

Hypophosphatemia after high-dose iron repletion with ferric carboxymaltose and ferric derisomaltose-the randomized controlled HOMe aFers study.

BACKGROUND: In patients with iron deficiency anemia, ferric carboxymaltose (FCM) and ferric derisomaltose (FDI) allow high-dose iron repletion. While FCM is reported to induce hypophosphatemia, the frequency of hypophosphatemia after an equivalent dosage of FDI had not been assessed prospectively. METHODS: In the prospective, single-center, double-blind HOMe aFers study, 26 women with iron deficiency anemia (hemoglobin < 12 g/dL plus either plasma ferritin ≤ 100 ng/mL or a plasma ferritin ≤ 300 ng/mL and transferrin saturation (TSAT) ≤ 30%) were randomized to a single intravenous infusion of 20 mg/kg body weight (up to a maximum of 1000 mg) FCM or FDI. The primary endpoint was the incidence of hypophosphatemia (plasma phosphorus levels < 2.0 mg/dL at day 1, day 7 ± 2, and/or day 35 ± 2 after the infusion). In order to investigate potential skeletal and cardiovascular implications, we assessed changes in other components of mineral and bone metabolism, left ventricular function, and arrhythmias. RESULTS: Hypophosphatemia occurred more frequently in women treated with FCM (9 out of 12 [75%]) than in those treated with FDI (1 out of 13 [8%]; p = 0.001). Within 24 h after iron supplementation, women in the FCM group had significant higher plasma intact FGF23 (p < 0.001) and lower plasma 1.25-dihydroxyvitamin D (p < 0.001). As an indicator of urinary phosphorus losses, urinary fractional phosphorus excretion was higher in the FCM group (p = 0.021 at day 7 ± 2 after iron supplementation). We did not observe differences in skeletal and cardiovascular markers, potentially because of the limited number of participants. CONCLUSIONS: While both FCM and FDI provide efficient iron repletion in participants with iron deficiency anemia, FCM induced hypophosphatemia more often than FDI. TRIAL REGISTRATION: Clinical Trials.gov NCT02905539. Registered on 8 September 2016. 2015-004808-36 (EudraCT Number) U1111-1176-4563 (WHO Universal Trial Number) DRKS00010766 (Deutsches Register Klinischer Studien).

[Evidence-based drug therapy for heart failure-an update]. / Aktuelles zur evidenzbasierten medikamentösen Herzinsuffizienztherapie.

Chronic heart failure affects millions of people worldwide and is associated with high morbidity and mortality. Because of steadily increasing ageing populations and improved survival rates after myocardial infarction, the incidence of chronic heart failure is rising. As acute decompensated heart failure is one of the leading causes for hospitalization in Germany, heart failure imposes a huge economic burden on its health care system. Guideline directed therapy is important to improve prognosis. In the following, we give an overview about novel heart failure clinical trial results and point to important comorbidities.

[Update on heart failure]. / Neues zur Herzinsuffizienz.

Heart failure is one of the leading diseases in internal medicine worldwide. Because of the increase in population aging, the incidence and prevalence of heart insufficiency is rising annually and is now the most frequent individual diagnosis among hospitalized patients in Germany. The mortality rate has recently been reduced, since new pharmacological options, especially the inhibition of neprilysin, have been developed; however, heart failure is still associated with a high mortality and morbidity rate. Thus, guideline-conform treatment is of crucial importance. This review highlights and summarizes the current scientific knowledge on heart failure from 2017 and 2018 based on the guidelines of the European Society of Cardiology. New aspects about heart failure with middle grade limitations of ejection fraction are firstly presented. Subsequently, innovative diagnostic and therapeutic strategies, new pharmacological developments and handling of frequent comorbidities in patients with heart failure are discussed.

[Valvular heart disease in patients with chronic kidney disease]. / Herzklappenvitien bei chronischer Niereninsuffizienz.

Valvular heart disease is a common comorbidity in patients with impaired renal function, especially in those with end-stage renal disease undergoing dialysis. Sclerosis and calcification of the heart valves and the valve ring are particularly relevant in the etiology of the diseases. These typically occur at the aortic and mitral valves and can lead to both insufficiency and stenosis of the affected valve. In the current guidelines of the European Society for Cardiology published in 2017, surgical treatment remains the standard of care for most forms of severe valvular heart disease; however, the presence of chronic kidney disease impairs clinical outcomes and is associated with higher mortality rates when compared to patients with preserved renal function. Catheter-based treatment options have emerged as an effective and safe alternative for patients >75 years and/or with increased surgical risk. Consequently, in patients with appropriate anatomy and elevated risk, interventional treatment options should also be discussed in the heart team.

[Cardiovascular pharmacotherapy and coronary revascularization in end-stage renal failure]. / Kardiovaskuläre Pharmakotherapie und koronare Revaskularisation bei terminaler Niereninsuffizienz.

There is a close physiological relationship between the kidneys and the heart. Cardiovascular diseases are the most prevalent cause of death in patients with chronic kidney disease (CKD), whereas CKD may directly accelerate the progression of cardiovascular diseases and is considered to be a cardiovascular risk factor. In patients with mild CKD, i.e. an estimated glomerular filtration rate (eGFR) >60 ml/min/1.73 m2, treatment of coronary artery disease and chronic heart failure is not essentially different from patients with preserved renal function; however, as most pivotal trials have systematically excluded patients with advanced renal failure, many treatment recommendations in this patient group are based on observational studies, post hoc subgroup analyses and meta-analyses or pathophysiological considerations, which are not supported by controlled studies. Therefore, prospective randomized studies on the management of heart failure and coronary artery disease are needed, which should specifically focus on the growing number of patients with advanced renal functional impairment.

[Multimodal diagnostic of CSNB1 with NYX gene mutation]. / Stufendiagnostik einer CSNB1 mit NYX-Genmutation.

This article presents the case of a young male patient with complete congenital stationary night blindness (CSNB1). The informative value of the general medical history and clinical findings for the diagnosis was impaired due to language barriers and low compliance. Full-field electroretinography and optical coherence tomography help to define particular hereditary retinal dystrophies. Molecular genetic analysis by next generation sequencing as a part of multimodal diagnostics finally uncovered a rare, causal missense mutation in the nyctalopin (NYX) gene.