Intensive receptor blockade and plasma exchange to treat refractory scleroderma renal crisis in patients with agonistic autoantibodies targeting the angiotensin II type 1 and endothelin-1 type A receptors.

Scleroderma renal crisis is a rare complication of systemic sclerosis characterized by a rapid decline in kidney function due to acute renal vascular injury. Recently, activating autoantibodies targeting the angiotensin II type 1 receptor and the endothelin-1 type A receptor have been implicated in the pathophysiology of scleroderma renal crisis by sensitizing the angiotensin II type 1 receptor and endothelin-1 type A receptor in renal resistance arteries to their natural ligands. Here, we describe a cohort of 10 patients with scleroderma renal crisis refractory to standard treatment, including blockade of the renin-angiotensin system. Multimodal therapy was initiated, targeting at the removal of anti-angiotensin II type 1 receptor and anti-endothelin-1 type A receptor autoantibodies by plasma exchange and the reduction of vasoconstrictive activity. Further treatment options included angiotensin II type 1 receptor and endothelin-1 type A receptor blockade, iloprost, intravenous immunoglobulins, and immunosuppression. Six patients were hypertensive. On kidney biopsy, concentric intimal sclerosis was present in all patients, whereas acute vascular injury was evident in eight. Levels of anti-angiotensin II type 1 receptor and anti-endothelin-1 type A receptor autoantibodies were significantly reduced by multimodal treatment. Kidney function improved in three patients with histological signs of severe acute renal vascular damage. This report demonstrates that intensive multimodal therapy taking account of potentially pathogenic anti-angiotensin II type 1 receptor and anti-endothelin-1 type A receptor autoantibodies in concert with other vasodilatory interventions provides a salvage option for patients with refractory scleroderma renal crisis.

Analysis of maternal mortality in Berlin, Germany - discrepancy between reported maternal mortality and comprehensive death certificate exploration.

OBJECTIVES: The Organisation for Economic Cooperation and Development (OECD) estimates an average maternal mortality rate (MMR) of around 3.4 maternal deaths per 100,000 live births for 2019-2021, based on relevant diagnoses on death certificates. However, Germany does not currently have a registry for recording the number of maternal deaths. The aim of this study is to identify the actual number of maternal deaths in Berlin between 2019 and 2022, as well as sources of underreporting and causes of death. METHODS: Potential maternal mortality cases were identified through a search at the Berlin Central Archive for Death Certificates, inquiring women aged 15-50 years with indications of present or recent pregnancy on the death certificate. To cross match the database, an additional search at the Charité University Hospital Berlin was carried out, checking each individual file for pregnancy-association. RESULTS: The data search resulted in 2,316 women, 18 of which presented an association to pregnancy. Of these, 12 could be classified as maternal mortality cases (MMR 7.8/100,000). The additional search in a university setting revealed two further maternal mortality cases without prior indication of pregnancy on the death certificate. This results in a total MMR of 9.1/100,000 live births, which is over double the official estimate by the OECD. CONCLUSIONS: Based on our findings in Berlin, it can be estimated that there is significant underreporting regarding maternal death cases in Germany. A more comprehensive recording system is needed to more accurately portray maternal mortality.

Anterior cruciate ligament laxity related to the menstrual cycle: an updated systematic review of the literature.

OBJECTIVES: The purpose of this study was to conduct a systematic review regarding the purported differences in anterior cruciate ligament (ACL) laxity throughout the course of the menstrual cycle. METHODS: A systematic review was performed by searching electronic databases, along with hand-searching of journals and reference tracking for any study that assessed ACL integrity throughout the menstrual cycle from 1998 until 2011. Studies that met the pre-defined inclusion criteria were evaluated using the Modified Sackett Score (MSS) instrument that assessed their methodological quality. RESULTS: Thirteen articles out of a possible 28 met the inclusion criteria. CONCLUSIONS: This systematic review found 13 clinical trials investigating the effect of the menstrual cycle on ACL laxity. There is evidence to support the hypothesis that the ACL changes throughout the menstrual cycle, with it becoming more lax during the pre-ovulatory (luteal) phase. Overall, these reviews found statistically significant differences for variation in ACL laxity and injury throughout the menstrual cycle, especially during the pre-ovulatory phase. Female athletes may need to take precautions in order to reduce the likelihood of ACL injury. However, the quality of the assessments was low and the evidence is still very limited. More and better quality research is needed in this area.

OBJECTIFS: Le but de cette étude était de procéder à un examen systématique concernant les prétendues différences dans le laxisme du ligament croisé antérieur (LCA) tout au long du cycle menstruel. MÉTHODOLOGIE: Un examen systématique a été effectué en recherchant des bases de données électroniques, ainsi qu'en effectuant une recherche manuelle des revues et un suivi de références pour toute étude de 1998 jusqu'en 2011 qui a évalué l'intégrité du ligament croisé antérieur LCA tout au long du cycle menstruel. Les études qui repondaient aux criteres d'inclusion predefinis ont ete evaluees en utilisant le score modifie de Sackett (MSS) qui a évalué la qualité de leur méthodologie. RÉSULTATS: Treize articles, sur un total possible de 28, répondaient aux critères d'inclusion. CONCLUSIONS: Cet examen systématique a découvert 13 essais cliniques portant sur l'effet du cycle menstruel sur le laxisme du LCA. Il existe des preuves pour étayer l'hypothèse que le LCA change tout au long du cycle menstruel, devenant plus relâché lors de la phase pré-ovulatoire (lutéale). Dans l'ensemble, ces examens ont montre des differences statistiquement significatives entre la variation de laxisme et de blessures du LCA tout au long du cycle menstruel, en particulier pendant la phase pré-ovulatoire. Les athlètes de sexe féminin devraient peut-être prendre des précautions pour réduire le risque de blessures du LCA. Cependant, les evaluations qualitatives etaient insuffisantes et les preuves sont encore très limitées. Donc, il faut effectuer plus de recherches, et de meilleure qualité, dans ce domaine.