Delayed orchidopexy for undescended testes has been associated with abnormal testicular histology, but the effect on later fertility is unknown. We aimed to establish the importance of the first postnatal maturational step-ie, the transformation of gonocytes into Ad (dark) spermatogonia on fertility. We matched histological findings of the testes from 31 patients who had undergone an early orchidopexy with their total number of sperm. If Ad spermatogonia were present, 17 (94%) of 18 (95% CI 72.7-99.9) of the men had a total sperm count of 40 x 10(6)/ejaculate or greater. By contrast, despite successful early surgery, if Ad spermatogonia were absent, 12 (92%) of 13, (64.0-99.8) patients had abnormal spermiograms. Thus, the transformation of gonocytes into Ad spermatogonia is crucial for male fertility.

The importance of both an early orchidopexy and germ cell maturation for fertility.

Lancet

Migraine affects about 1 billion people worldwide, and up to 15% of adults in the United States have migraine attacks in any given year. Migraine is associated with substantial adverse socioeconomic and personal effects. It is the second leading cause of years lived with disability worldwide for all ages and the leading cause in women aged 15 to 49 years. Diagnostic uncertainty increases the likelihood of unnecessary investigations and suboptimal management. This article advises clinicians about diagnosing migraine, ruling out secondary headache disorders, developing acute and preventive treatment plans, and deciding when to refer the patient to a specialist.

Migraine.

Annals of Internal Medicine

Iron deficiency (ID) is the most common nutritional disorder worldwide. It is often observed in patients with chronic diseases, such as heart failure (HF), chronic kidney disease (CKD), inflammatory bowel disease (IBD) and cancer. ID is associated with poor clinical outcome, including poor performance, reduced quality of life, as well as increased hospitalization and mortality. The aim of this review is to provide an overview about the role of ID in chronic diseases (HF, CKD, IBD, cancer) regarding their current definitions and clinical relevance; diagnostic accuracy of iron parameters in chronic inflammatory conditions and its potential as prognostic markers. Due to different definitions and guideline recommendations of ID, various laboratory parameters for ID diagnostic exist and there is no general consensus about the definition of ID and its treatment. Still, a general trend can be observed across all investigated indications of this review (HF, CKD, IBD, cancer) that serum ferritin and transferrin saturation (TSAT) are the two parameters mentioned most often and emphasized in all guidelines to define ID and guide treatment. The most commonly used threshold values for the diagnosis of ID are TSAT of&#x2009;&lt;&#x2009;20% and serum ferritin of&#x2009;&lt;&#x2009;100-300&#xa0;&#xb5;g/L. Noteworthy, both TSAT and particularly ferritin are frequently applied, but both may vary due to inflammatory conditions. Studies showed that TSAT is less affected by inflammatory processes and may therefore be more accurate and reliable than serum ferritin, particularly in conditions with elevated inflammatory state. A low iron status and particularly a low TSAT value was associated with a poor outcome in all investigated indications, with the strongest evidence in HF patients. Routine surveillance of iron status in these groups of patients with chronic conditions is advisable to detect ID early. Depending on the inflammatory state, TSAT&#x2009;&lt;&#x2009;20% may be the more accurate diagnostic marker of ID than ferritin. Moreover, TSAT may also be the more reliable estimate for the prognosis, particularly in HF.

How to diagnose iron deficiency in chronic disease: A review of current methods and potential marker for the outcome.

European Journal of Medical Research

Long COVID is an often debilitating illness that occurs in at least 10% of severe acute respiratory syndrome coronavirus&#xa0;2 (SARS-CoV-2) infections. More than 200 symptoms have been identified with impacts on multiple organ systems. At least 65 million individuals worldwide are estimated to have long COVID, with cases increasing daily. Biomedical research has made substantial progress in identifying various pathophysiological changes and risk factors and in characterizing the illness; further, similarities with other viral-onset illnesses such as myalgic encephalomyelitis/chronic fatigue syndrome and postural orthostatic tachycardia syndrome have laid the groundwork for research in the field. In this Review, we explore the current literature and highlight key findings, the overlap with other conditions, the variable onset of symptoms, long COVID in children and the impact of vaccinations. Although these key findings are critical to understanding long COVID, current diagnostic and treatment options are insufficient, and clinical trials must be prioritized that address leading hypotheses. Additionally, to strengthen long COVID research, future studies must account for biases and SARS-CoV-2 testing issues, build on viral-onset research, be inclusive of marginalized populations and meaningfully engage patients throughout the research process.

Long COVID: major findings, mechanisms and recommendations.

Nature Reviews. Microbiology

Diabetic kidney disease is highly prevalent in patients with type 2 diabetes and is a major cause of end-stage renal disease in Switzerland. Patients with diabetic kidney disease are among the most complex patients in diabetes care. They require a multifactorial and multidisciplinary approach with the goal to slow the decline in glomerular filtration rate (GFR) and cardiovascular morbidity. With this consensus we propose an evidence-based guidance to health care providers involved in the care of type 2 diabetic patients with diabetic kidney disease.First, there is a need to increase physician awareness and improve screening for diabetic kidney disease as early intervention may improve clinical outcomes and the financial burden. Evaluation of estimated GFR (eGFR) and spot urine albumin/creatinine ratio is recommended at least annually. Once it is diagnosed, glucose control and optimisation of blood pressure control with renin-angiotensin system blockers have been recommended as mainstay management of diabetic kidney disease for more than 20 years. Recent, high quality randomised controlled trials have shown that sodium-glucose cotransporter-2 (SGLT2) inhibition slows eGFR decline and cardiovascular events beyond glucose control. Likewise, mineralocorticoid receptor antagonism with finerenone has cardiorenal protective effects in diabetic kidney disease. Glucagon-like peptide-1 (GLP1) receptor agonists improve weight loss if needed, and decrease albuminuria and cardiovascular morbidity. Lipid control is also important to decrease cardiovascular events. All these therapies are included in the treatment algorithms proposed in this consensus. With advancing kidney failure, other challenges may rise, such as hyperkalaemia, anaemia and metabolic acidosis, as well as chronic kidney disease-mineral and bone disorder. These different topics and treatment strategies are discussed in this consensus. Finally, an update on diabetes management in renal replacement therapy such as haemodialysis, peritoneal dialysis and renal transplantation is provided. With the recent developments of efficient therapies for diabetic kidney disease, it has become evident that a consensus document is necessary. We are optimistic that it will significantly contribute to a high-quality care for patients with diabetic kidney disease in Switzerland in the future.

Diabetic kidney disease in type 2 diabetes: a consensus statement from the Swiss Societies of Diabetes and Nephrology.

Swiss Medical Weekly

The association of chronic heart failure (CHF) and iron deficiency (ID) with or without anemia is frequently encountered in current medical practice and has a negative prognostic impact, worsening patients' exercise capacity and increasing hospitalization costs. Moreover, anemia is common in patients with chronic kidney disease (CKD) and CHF, an association known as cardio-renal anemia syndrome (CRAS) possessing a significantly increased risk of death.

This review aims to provide an illustrative survey on the impact of ID in CHF patients-based on physiopathological traits, clinical features, and the correlation between functional and absolute ID with CHF-and the benefit of iron supplementation in CHF.

We selected the most recent publications with important scientific content covering the association of CHF and ID with or without anemia.

An intricate physiopathological interplay is described in these patients-decrease in erythropoietin levels, activation of the renin-angiotensin-aldosterone system, systemic inflammation, and increases in hepcidin levels. These mechanisms amplify anemia, CHF, and CKD severity and worsen patients' outcomes.

Anemia is frequently encountered in CHF and represents a negative prognostic factor. Data from randomized controlled trials have underlined the administration of intravenous iron therapy (ferric carboxymaltose) as the only viable treatment option, with beneficial effects on quality of life and exercise capacity in patients with ID and systolic heart failure.

Role of Iron Deficiency in Heart Failure-Clinical and Treatment Approach: An Overview.

Diagnostics

Hyponatremia is commonly encountered in the setting of heart failure, especially in decompensated, fluid-overloaded patients. The pathophysiology of hyponatremia in patients with heart failure is complex, including numerous mechanisms: increased activity of the sympathetic nervous system and the renin-angiotensin-aldosterone system, high levels of arginine vasopressin and diuretic use. Symptoms are usually mild but hyponatremic encephalopathy can occur if there is an acute decrease in serum sodium levels. It is crucial to differentiate between dilutional hyponatremia, where free water excretion should be promoted, and depletional hyponatremia, where administration of saline is needed. An inappropriate correction of hyponatremia may lead to osmotic demyelination syndrome which can cause severe neurological symptoms. Treatment options for hyponatremia in heart failure, such as water restriction or the use of hypertonic saline with loop diuretics, have limited efficacy. The aim of this review is to summarize the principal mechanisms involved in the occurrence of hyponatremia, to present the main guidelines for the treatment of hyponatremia, and to collect and analyze data from studies which target new treatment options, such as vaptans.

The importance of both an early orchidopexy and germ cell maturation for fertility.

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