Collateral artery growth (arteriogenesis) after experimental arterial occlusion is impaired in mice lacking CC-chemokine receptor-2

Arteriogenesis has been associated with the presence of monocytes/macrophages within the collateral vessel wall. Induced macrophage migration in vivo is driven by the binding of monocyte chemoattractant protein-1 (MCP-1, or CCL2 in the new nomenclature) to the CCR2-chemokine receptor on macrophages. To determine whether the CCL2-CCR2 signaling pathway is involved in the accumulation of macrophages in growing collateral vessels, we used mice that are deficient in CCR2 in a model of experimental arterial occlusion and collateral vessel growth. In an in vitro CCL2-driven chemotaxis assay, mononuclear cells isolated from wild-type BALB/c mice exhibited CCL2 concentration-dependent migration, whereas this migration was abolished in cells from CCR2(-/-) mice on a BALB/c genetic background. In vivo, blood flow recovery as measured by laser Doppler (LDI) and MRI (MRI) was impaired in CCR2(-/-) mice on either the BALB/c or C57BL/6 genetic backgrounds. Three weeks after femoral artery ligation, LDI perfusion ratio of operated versus nonoperated distal hindlimb in BALB/c wild-type mice increased to 0.45+/-0.06 and in CCR2(-/-) animals only to 0.21+/-0.03 (P<0.01). In C57BL/6 mice, ratio increased to 0.96+/-0.09 and 0.85+/-0.08 (P<0.05), respectively. MRI at 3 weeks (0.76+/-0.06 versus 0.62+/-0.01; P<0.05) and hemoglobin oxygen saturation measurements confirmed these findings. Active foot movement score significantly decreased and gastrocnemius muscle atrophy was significantly greater in CCR2(-/-) mice. Morphometric analysis showed a lesser increase in collateral vessel diameters in CCR2(-/-) mice. Importantly, the number of invaded monocytes/macrophages in the perivascular space of collateral arteries of CCR2(-/-) animals was dramatically reduced in comparison to wild-type mice. In conclusion, our results demonstrate that the CCR2 signaling pathway is essential for efficient collateral artery growth.     

Maternal mortality in Pernambuco, Brazil: what has changed in ten years?

This study examines changes in levels and patterns of maternal mortality in Pernambuco, Brazil, in 1994 and 2003. The research was carried out in five sub-regions of Pernambuco using the Reproductive Age Mortality Survey (RAMOS) method and based on death certificates of women of reproductive age registered in the local System of Information on Mortality. In-depth interviews with family members were also conducted for the abortion-related deaths. Of the 1,258 female deaths investigated, 54 maternal deaths were identified, corresponding to a maternal mortality ratio of 77 per 100,000 live births. The estimated level of under-reporting (46%) corresponds to an upward adjustment factor of 1.9. The illegal status of abortion in Brazil remains an important contributory factor for the abortion-related deaths. Approximately 94% of the maternal deaths were judged to be avoidable with improvements in health care. Maternal mortality declined by 30% over the ten-year period but the level of misclassification of maternal deaths remains. Improvements in maternity care for women and reporting of maternal deaths are still urgently needed.     

Deep-hidden anastomoses in monochorionic twin placentae are harmless

OBJECTIVES: Our objective was to identify the clinical consequences of deep-hidden anastomoses that occur underneath the placental surface. METHODS: Twelve placentae that underwent intrauterine laser ablation of placental anastomoses for twin-twin transfusion syndrome (TTTS) and 14 non-TTTS controls were investigated for deep-hidden anastomoses. Additionally, we investigated the inter-twin haemoglobin differences as an indicator for fetofetal transfusion. Placentae were divided into four groups: TTTS placentae without residual chorionic-plate anastomoses without deep-hidden anastomoses (group 1) and with deep-hidden anastomoses (group 2), and non-TTTS placentae with chorionic-plate anastomoses without deep-hidden anastomoses (group 3) and with deep-hidden anastomoses (group 4). RESULTS: Deep-hidden anastomoses were identified in 58% (7/12) of the TTTS placentae after laser surgery and in 64% (9/14) of the non-TTTS placentae. Groups 1 and 2 had equal inter-twin haemoglobin differences: medians 1.4 and 1.2 gr/dL, respectively (p = 0.48). In group 3, the median inter-twin haemoglobin difference without deep-hidden anastomoses was 2.6 gr/dL (group 3) and with deep-hidden anastomoses (group 4) it was 5.1 gr/dL (p = 0.26). CONCLUSION: Both comparisons imply that deep-hidden anastomoses did not cause any additional increase in Hb difference. In conclusion, haematological and additional hemodynamical analysis show that deep-hidden anastomoses are likely to occur without any clinical consequences.     

Treatment with amniopatch of premature rupture of membranes after first-trimester chorionic villus sampling

OBJECTIVE: To assess the amniopatch procedure when premature rupture of membranes occurs after first-trimester chorionic villus sampling (CVS). STUDY DESIGN: From May 2001 to June 2004, the amniopatch procedure was offered in cases of premature rupture of membranes after CVS when severe oligohydramnios was present (largest vertical pocket < 2 cm) and persistent (more than 1 week). RESULTS: The amniopatch was placed in five pregnancies at 12-18 weeks of gestation, resulting in amniotic fluid restoration in all but one pregnancy. In three pregnancies, fetal demise was observed at 1, 2 and 36 days after the procedure. The last procedure resulted in a healthy newborn. CONCLUSION: Although the amniopatch restored normal amniotic fluid levels in all cases, 4 of the 5 cases resulted in fetal demise.     

Utility of screening for other causes of infertility in women with "known" polycystic ovary syndrome

We investigated the prevalence of abnormal screening results (questionnaire and testing for other causes of oligo-ovulation, male or tubal factor infertility) in a group of 1,313 oligo-ovulatory women (included and excluded subjects) whose condition was screened for inclusion in the Pregnancy in Polycystic Ovary Syndrome trial, a multicenter clinical trial that was conducted at 13 sites in the United States. Other than failure to demonstrate laboratory evidence of hyperandrogenemia, the most common reasons for subject exclusion were persistent oligospermia and tubal factor infertility.     

Innovations ‘Out of Place’: Controversies Over IVF Beginnings in India Between 1978 and 2005

ABSTRACT

In 1978, the year the first in vitro fertilization (IVF) baby was born in the United Kingdom, a research team in Kolkata reported that it too had successfully produced an IVF baby in India. However, the claim was dismissed at the time, because the experiment was conducted outside authorized institutions and recognized centers of innovation—in short, because it was an innovation ‘out of place.’ Tracing controversies over the case between 1978 and 2005, I show the importance of space or place in processes of knowledge production and recognition. Further, I explain the initial repudiation and subsequent partial recognition of the claim through shifts in the landscape of legitimate spaces of innovation. By discussing this specific case of the production of science and technology in the Global South, I challenge conventional narratives of diffusion that are prevalent in studies on the worldwide proliferation of reproductive technologies.     

Performance Characteristics of Real-Time PCRs for African Swine Fever Virus Genome Detection—Comparison of Twelve Kits to an OIE-Recommended Method

African swine fever (ASF) is a major threat to pig production, and real-time PCR (qPCR) protocols are an integral part of ASF laboratory diagnosis. With the pandemic spread of ASF, commercial kits have risen on the market. In Germany, the kits have to go through an approval process and thus, general validation can be assumed. However, they have never been compared to each other. In this study, 12 commercial PCR kits were compared to an OIE-recommended method. Samples representing different matrices, genome loads, and genotypes were included in a panel that was tested under diagnostic conditions. The comparison included user-friendliness, internal controls, and the time required. All qPCRs were able to detect ASFV genome in different matrices across all genotypes and disease courses. With one exception, there were no significant differences when comparing the overall mean. The overall specificity was 100% (95% CI 87.66–100), and the sensitivity was between 95% and 100% (95% CI 91.11–100). As can be expected, variability concerned samples with low genome load. To conclude, all tests were fit for purpose. The test system can therefore be chosen based on compatibility and prioritization of the internal control system.     

Patterns of Pretreatment Diagnostic Assessment in Patients Treated with Stereotactic Body Radiation Therapy (SBRT) for Non-Small Cell Lung Cancer (NSCLC): Special Characteristics in the COVID Pandemic and Influence on Outcomes

The pandemic raised a discussion about the postponement of medical interventions for non-small cell lung cancer (NSCLC). We analyzed the characteristics of pretreatment diagnostic assessment in the pandemic and the influence of diagnostic assessment on outcomes. A total of 96 patients with stereotactic body radiation therapy (SBRT) for NSCLC were included. The number of patients increased from mean 0.9 (2012–2019) to 1.45 per month in the COVID era (p < 0.05). Pandemic-related factors (contact reduction, limited intensive care unit resources) might have influenced clinical decision making towards SBRT. The time from pretreatment assessment (multidisciplinary tumor board decision, bronchoscopy, planning CT) to SBRT was longer during the COVID period (p < 0.05). Reduced services, staff shortage, or appointment management to mitigate infection risks might explain this finding. Overall survival, progression-free survival, locoregional progression-free survival, and distant progression-free survival were superior in patients who received a PET/CT scan prior to SBRT (p < 0.05). This supports that SBRT guidelines advocate the acquisition of a PET/CT scan. A longer time from PET/CT scan/conventional staging to SBRT (<10 vs. ≥10 weeks) was associated with worse locoregional control (p < 0.05). The postponement of diagnostic or therapeutic measures in the pandemic should be discussed cautiously. Patient- and tumor-related features should be evaluated in detail.     

Rationale and design of the AdaptResponse trial: a prospective randomized study of cardiac resynchronization therapy with preferential adaptive left ventricular‐only pacing

The AdaptResponse trial is designed to test the hypothesis that preferential adaptive left ventricular‐only pacing with the AdaptivCRT^® algorithm reduces the incidence of the combined endpoint of all‐cause mortality and intervention for heart failure (HF) decompensation, compared with conventional cardiac resynchronization therapy (CRT), among patients with a CRT indication, left bundle branch block (LBBB) and normal atrioventricular (AV) conduction. The AdaptResponse study is a prospective, randomized, controlled, single‐blinded, multicentre, clinical trial ( ClinicalTrials.gov Identifier: NCT02205359), conducted at up to 200 centres worldwide. Following enrolment and baseline assessment, eligible subjects will be implanted with a CRT system containing the AdaptivCRT algorithm, and randomized in a 1:1 fashion to either a treatment (‘AdaptivCRT’) or control (‘Conventional CRT’) group. The study is designed to observe a primary endpoint in 1100 patients (‘event‐driven’) and approximately 3000 patients will be randomized. The primary endpoint is the composite of all‐cause mortality and intervention for HF decompensation; secondary endpoints include all‐cause mortality, intervention for HF decompensation, clinical composite score (CCS) at 6 months, atrial fibrillation, quality of life measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ), health outcome measured by the EQ‐5D instrument, all‐cause readmission after a HF admission, and cost‐effectiveness. The AdaptResponse clinical trial is powered to assess clinical endpoints and is expected to provide definitive evidence on the incremental utility of AdaptivCRT‐enhanced CRT systems.