Treatment of distal third humeral shaft fractures with posterior minimally invasive plate osteosynthesis (MIPO) with segmental isolation of the radial nerve: minimum one-year follow-up.

Background: Open reduction and internal fixation with plate is one of the most widely used treatments for distal third humeral shaft fractures. The purpose of this study was to report the outcomes of the treatment of distal third humeral shaft fractures with posterior minimally invasive plate osteosynthesis (MIPO) with segmental isolation of the radial nerve. Methods: We performed an observational, retrospective, consecutive, monocentric, continuous multioperator study. We reviewed 22 distal third humeral shaft fractures treated with posterior MIPO in our institution with an extra-articular distal humerus plate from 2018 to 2021. Inclusion was limited to functionally independent patients with displaced fractures involving the junction of the middle and distal thirds of the humerus and minimum 12-month follow-up for implant removal. We assessed clinical outcomes including range of motion; QuickDASH score; Mayo Elbow Performance Score; and Constant-Murley score. Results: The average follow-up period of the sample was 31.7 ± 11.6 months (range, 15.7-51.3 months). The average elbow flexion and extension were 146.4° ± 7.3° (range, 120°-150°) and -0.7° ± 3.3° (range, -15° to 0°), respectively. The average shoulder anterior flexion, elevation, and abduction were 178.6° ± 3.6° (range, 170°-180°), 179.1° ± 2.9° (range, 170°-180°), and 140.9° ± 14.8° (range, 110°-160°), respectively. The average external rotation was 88.6° ± 6.4 (range, 65°-90°). The mean visual analog scale score for pain was 1.0 ± 1.6 (range, 0-5) and the mean Mayo Elbow Performance Score was 90.5 ± 9.9 (range, 70-100). The mean QuickDASH and Constant-Murley scores were 4.7 ± 6.8 (range, 0-20.5) and 95.5 ± 5.1 (range, 81-100), respectively. Two patients presented with relevant compromise of radial nerve motor function postoperatively (M3 and M2; the more compromised was preoperative injury). All patients recovered radial nerve neuropraxia within six weeks postoperatively. All fractures achieved union. The average anteroposterior and lateral axis were 175.0 ± 3.6 (168.0°-180.0°) and 177.5 ± 2.0 (173.0°-180.0°), respectively. No superficial or deep infection was reported. No cases of re-displacement of fracture, implant failure, or any other implant-related complication in follow-up were reported. No patient required plate withdrawal. Conclusion: The results of this study demonstrate that the posterior MIPO technique is a reliable option for treating distal third shaft humeral fractures. The radial nerve must be identified and protected in all cases to prevent palsy.

Biosimilars approvals by thirteen regulatory authorities: A cross-national comparison.

Biosimilars are biological medicines highly similar to a previously licensed reference product and their licensing is expected to improve access to biological therapies. This study aims to present an overview of biosimilars approval by thirteen regulatory authorities (RA). The study is a cross-national comparison of regulatory decisions involving biosimilars in Argentina, Australia, Brazil, Chile, Canada, Colombia, Europe, Hungary, Guatemala, Italy, Mexico, Peru and United States. We examined publicly available documents containing information regarding the approval of biosimilars and investigated the publication of public assessment reports for registration applications, guidelines for biosimilars licensing, and products approved. Data extraction was conducted by a network of researchers and regulatory experts. All the RA had issued guidance documents establishing the requirements for the licensing of biosimilars. However, only three RA had published public assessment reports for registration applications. In total, the investigated jurisdictions had from 19 to 78 biosimilars approved, most of them licensed from 2018 to 2020. In spite of the advance in the number of products in recent years, some challenges still persist. Limited access to information regarding the assessment of biosimilars by RA can affect confidence, which may ultimately impact adoption of these products in practice.

Invasive Meningococcal Disease and COVID-19 Co-Infection: A Case Report.

This case report presents a 53-year-old male patient infected with COVID-19 who developed acute respiratory distress syndrome (ARDS) and septic shock due to meningococcemia, despite the absence of clinical signs of meningitis. This patient's condition was complicated by pneumonia in the setting of myocardial failure. In the curse of the disease, it is remarked that the importance of early recognition of sepsis symptoms is crucial in distinguishing patients with COVID-19 from those with other infections and preventing fatal outcomes. The case presented an excellent opportunity to review meningococcal disease's intrinsic and extrinsic risk factors. With the identified risk factors, we propose different measures to be considered to diminish and recognize this fatal disease early.

The floral biology and the role of staminal connective appendages during pollination of the endoparasite Bdallophytum americanum (Cytinaceae).

Bdallophytum americanum (Cytinaceae) is an endoparasitic plant species, meaning only the flowers emerge from the host during the reproductive season. Reports on the pollination biology of this species state that its primary pollinators are carrion flies attracted by the smell of the flowers and nectar as a reward. However, the functional role of one of the most outstanding attributes of B. americanum has been neglected. These are the staminal appendages formed by the apical overgrowth of connective tissue during anther development. To determine whether these staminal appendages play a role in pollination, we monitored a nectarless population of B. americanum. We described the inflorescence emergence, floral movements, and pollination and performed field experiments to test whether the absence of the staminal connective appendages affected the visitation frequency. Male inflorescences emerge early, and both male and female flowers open during the day and do not close. Hoverflies are the most frequent visitors to both floral sexes and carry the most pollen. Moreover, the movement of staminal appendages matching the pollen viability changes is reported for the first time. The staminal appendages are the structures where pollinators land before foraging. The field experiments showed that the visitation frequency decreased sharply without staminal appendages. As a landing platform, the staminal connective appendages in B. americanum are crucial for pollinator positioning and collecting viable pollen.

Cohesin-independent STAG proteins interact with RNA and R-loops and promote complex loading.

Most studies of cohesin function consider the Stromalin Antigen (STAG/SA) proteins as core complex members given their ubiquitous interaction with the cohesin ring. Here, we provide functional data to support the notion that the SA subunit is not a mere passenger in this structure, but instead plays a key role in the localization of cohesin to diverse biological processes and promotes loading of the complex at these sites. We show that in cells acutely depleted for RAD21, SA proteins remain bound to chromatin, cluster in 3D and interact with CTCF, as well as with a wide range of RNA binding proteins involved in multiple RNA processing mechanisms. Accordingly, SA proteins interact with RNA, and R-loops, even in the absence of cohesin. Our results place SA1 on chromatin upstream of the cohesin ring and reveal a role for SA1 in cohesin loading which is independent of NIPBL, the canonical cohesin loader. We propose that SA1 takes advantage of structural R-loop platforms to link cohesin loading and chromatin structure with diverse functions. Since SA proteins are pan-cancer targets, and R-loops play an increasingly prevalent role in cancer biology, our results have important implications for the mechanistic understanding of SA proteins in cancer and disease.

JAZF1-SUZ12 dysregulates PRC2 function and gene expression during cell differentiation.

Polycomb repressive complex 2 (PRC2) methylates histone H3 lysine 27 (H3K27me3) to maintain gene repression and is essential for cell differentiation. In low-grade endometrial stromal sarcoma (LG-ESS), the PRC2 subunit SUZ12 is often fused with the NuA4/TIP60 subunit JAZF1. We show that JAZF1-SUZ12 dysregulates PRC2 composition, genome occupancy, histone modification, gene expression, and cell differentiation. Loss of the SUZ12 N terminus in the fusion protein abrogates interaction with specific PRC2 accessory factors, reduces occupancy at PRC2 target genes, and diminishes H3K27me3. Fusion to JAZF1 increases H4Kac at PRC2 target genes and triggers recruitment to JAZF1 binding sites during cell differentiation. In human endometrial stromal cells, JAZF1-SUZ12 upregulated PRC2 target genes normally activated during decidualization while repressing genes associated with immune clearance, and JAZF1-SUZ12-induced genes were also overexpressed in LG-ESS. These results reveal defects in chromatin regulation, gene expression, and cell differentiation caused by JAZF1-SUZ12 that may underlie its role in oncogenesis.

CircZNF609 as a prototype to elucidate the biological function of circRNA-mRNA interactions.

Circular RNAs (circRNAs) are expressed and are regulated in many biological processes but little is known about their ability to directly control mRNA homeostasis. We show that circRNA zinc finger protein 609 (circZNF609) interacts with several mRNAs increasing the final protein levels, which in the case of the cytoskeleton-associated protein 5 (CKAP5) leads to a stabilized microtubule cytoskeleton and an enhanced tumor cell proliferation.

Data sources for drug utilization research in Latin American countries-A cross-national study: DASDUR-LATAM study.

PURPOSE: Drug utilization research (DUR) contributes to inform policymaking and to strengthen health systems. The availability of data sources is the first step for conducting DUR. However, documents that systematize these data sources in Latin American (LatAm) countries are not known. We compiled the potential data sources for DUR in the LatAm region. METHODS: A network of DUR experts from nine LatAm countries was assembled and experts conducted: (i) a website search of the government, academic, and private health institutions; (ii) screening of eligible data sources, and (iii) liaising with national experts in pharmacoepidemiology (via an online survey). The data sources were characterized by accessibility, geographic granularity, setting, sector of the data, sources and type of the data. Descriptive analyses were performed. RESULTS: We identified 125 data sources for DUR in nine LatAm countries. Thirty-eight (30%) of them were publicly and conveniently available; 89 (71%) were accessible with limitations, and 18 (14%) were not accessible or lacked clear rules for data access. From the 125 data sources, 76 (61%) were from the public sector only; 46 (37%) were from pharmacy records; 43 (34%) came from ambulatory settings and; 85 (68%) gave access to individual patient-level data. CONCLUSIONS: Although multiple sources for DUR are available in LatAm countries, the accessibility is a major challenge. The procedures for accessing DUR data should be transparent, feasible, affordable, and protocol-driven. This inventory could permit a comparison of drug utilization between countries identifying potential medication-related problems that need further exploration.

Impact of Cell of Origin on Outcomes After Autologous Hematopoietic Cell Transplant in Diffuse Large B-Cell Lymphoma.

Germinal center B-cell-like diffuse large B cell lymphoma (GCB-DLBCL) at diagnosis is associated with superior long-term outcomes compared to non-GCB-DLBCL in patients treated with conventional chemo-immunotherapy. Whether cell of origin (COO) by Hans algorithm retains its prognostic significance in patients with (R/R) relapsed/refractory DLBCL undergoing autologous hematopoietic cell transplant (auto-HCT) is not well established. Three hundred and fifty-seven patients underwent auto-HCT between 2005 and 2018. The COO status was determined in 284 patients and these were included in the analysis. One hundred ninety-four patients had GCB-DLBCL while 90 had non-GCB-DLBCL. Median follow up was 1.7 (0-13) years. The GCB-DLBCL was associated with inferior 5-year overall survival at 44% (95%CI, 36-52) versus 64% (95%CI, 54-77) (P = .004) and a higher relapse incidence at 67% (95%CI, 58-74) versus 49% (95%CI, 35-60) (P = .01) in the non-GCB-DLBCL. The difference between GCB and non-GCB-DLBCL remained statistically significant in multivariate analysis. Additionally, response at the time of transplant was an independent prognostic factor. GCB-DLBCL was enriched in double-hit and triple hit phenotype based on available fluorescence in situ hybridization data. These results suggest an enrichment of high-risk genetic rearrangements in R/R GCB-DLBCL resulting in limited efficacy of auto-HCT.

Cardiovascular autonomic responses during head-up tilt test in newly diagnosed type 2 diabetes.

BACKGROUND: Autonomic dysfunction is commonly observed in patients with long-standing type 2 diabetes. Previous studies have confirmed the value of both subjectively assessed symptoms and objective measurements of autonomic nervous system function in diagnosing cardiovascular autonomic neuropathy. However, the head-up tilt test (HUTT) has been rarely used to investigate cardiovascular autonomic responses in subjects with high risk of newly diagnosed type 2 diabetes (nT2D). OBJECTIVE: To evaluate autonomic cardiovascular responses through passive orthostatic challenge along the diabetes continuum. METHODS: The study population was stratified as normoglycemic (n = 16), prediabetes (n = 20), and nT2D (n = 20). The prevalence of orthostatic intolerance and autonomic cardiovascular responses was evaluated with the Task Force Monitor during a 30-min passive HUTT. Spectral indices of heart rate and blood pressure variability and baroreceptor effectiveness index (BEI) were calculated through the HUTT. BEI was obtained by the sequence method. RESULTS: There were no differences in the prevalence of orthostatic intolerance or in the indices of heart rate and blood pressure variability among the three groups of study. The BEI was attenuated in the nT2D group in supine rest and throughout HUTT compared with normoglycemic and prediabetes groups. The multivariable linear regression analysis showed that BEI was associated with fasting glucose (ß = - 0.52, p < 0.001) and HbA1c (ß = - 0.57, p  < 0.001) independently of cardiovascular risk factors. CONCLUSION: Cardiovascular autonomic neuropathy, expressed as blunted BEI, is the only abnormal autonomic nervous test detected in nT2D, and it was independently associated with fasting glucose and HbA1c values.

Circular RNA ZNF609/CKAP5 mRNA interaction regulates microtubule dynamics and tumorigenicity.

Circular RNAs (circRNAs) are widely expressed in eukaryotes and are regulated in many biological processes. Although several studies indicate their activity as microRNA (miRNA) and protein sponges, little is known about their ability to directly control mRNA homeostasis. We show that the widely expressed circZNF609 directly interacts with several mRNAs and increases their stability and/or translation by favoring the recruitment of the RNA-binding protein ELAVL1. Particularly, the interaction with CKAP5 mRNA, which interestingly overlaps the back-splicing junction, enhances CKAP5 translation, regulating microtubule function in cancer cells and sustaining cell-cycle progression. Finally, we show that circZNF609 downregulation increases the sensitivity of several cancer cell lines to different microtubule-targeting chemotherapeutic drugs and that locked nucleic acid (LNA) protectors against the pairing region on circZNF609 phenocopy such effects. These data set an example of how the small effects tuned by circZNF609/CKAP5 mRNA interaction might have a potent output in tumor growth and drug response.

Transparency of data on the value chain of medicines in Argentina, Brazil, and Colombia.

Introduction: The transparency of data on the value chain of medicines is crucial for the study and monitoring of the pharmaceutical system. These data may impact medicine pricing negotiations, contribute to patient access to pharmaceutical products, and strengthen health systems. Objective: This study analyzed the national strategies to ensure the transparency of data from medicine cost development to marketing in Argentina, Brazil, and Colombia. Method: A descriptive study was carried out by searching databases, reports, documents, and scientific articles published between January and August 2022 related to rules on transparency and databases, including 1) marketing authorization; 2) pricing; 3) intellectual property; 4) clinical trials; 5) research and development (R&D); and 6) health technology assessment (HTA) of selected biopharmaceuticals. Results: Transparency data, rules, and information are not uniform. The infostructures (organizational capacity for collecting and distributing information) regarding the pharmaceutical value chain in these three countries face limitations in appropriate measures to publicly share data and evidence, including pre-clinical data, clinical data, and costs. None of the countries require transparency about data on research and development costs. All three countries present similar publicization of data on marketing authorization and intellectual property, with some differences. The significant limitations in Argentina include the absence of formal price regulation and data on the volume of medicine purchased and respective amounts paid. Among the three countries, Brazil showed a higher degree of information transparency, perhaps due to the legal regulation that guarantees citizens access to information of public interest. Brazil also stands out in terms of the public availability of HTA reports and pricing, in addition to the highest volume of information. In contrast, Colombia has in place a decree that allows 5 years of trial data exclusivity for new medicines, an act contrary to data transparency. Despite the different stages of transparency, no country has evidenced a robust use of these data in public policy decision-making. Conclusion: The results reinforce the presence of information asymmetry between stakeholders, data fragmentation, data gaps and overlap, and difficulty in comparing available data across the three countries and the use of these data nationally to produce evidence.

Nb/a-Si/Nb-junction Josephson arbitrary waveform synthesizers for quantum information.

We demonstrate Josephson arbitrary waveform synthesizers (JAWS) with increased operating temperature range for temperatures below 4 K. These JAWS synthesizers were fabricated with externally-shunted Nb/a-Si/Nb junctions whose critical current exhibits improved temperature stability compared to the self-shunted Nb/Nb0.15Si0.85/Nb junctions typically used. Vertical stud resistors made of 230 nm of PdAu were developed to provide the milliohm shunt resistance required for junction overdamping while maintaining a small footprint suitable for high-density series arrays embedded in a coplanar waveguide. We evaluated the performance of these resistors from 3.8 K down to 20 mK. We designed, fabricated and tested a JAWS circuit with 4650 externally shunted Nb/a-Si/Nb JJs with a critical current density (Jc) of 0.12 mA∕µm2 and critical current (Ic) of 3 mA. This circuit was designed to be mounted to the 3 K stage of a dilution refrigerator and used to control and calibrate a qubit mounted at the 10 mK stage. To increase the circuit density of the JAWS circuits we made arrays of two-junction vertical stacks. Current-voltage (I-V) curves of this JAWS circuit with stacked junctions under microwave excitation show Shapiro steps with quantum-locking ranges similar to those of JAWS circuits used for qubit control.

Presión y área de contacto en reparación de manguito rotador: una revisión sistemática / Pressure and contact area in rotator cuff repair: a systematic review

OBJETIVO Proporcionar una sinopsis exhaustiva y un análisis de los estudios biomecánicos sobre la magnitud y distribución de la presión en la interfase tendón-huella de las roturas del manguito rotador, informadas en la literatura en los últimos cinco años. MÉTODOS La investigación se realizó de acuerdo con los métodos descritos en el Manual Cochrane. Los resultados se informan de acuerdo con el consenso de Ítems Preferidos de Reporte en Revisiones Sistemáticas y Metaanálisis (Preferred Reporting Items for Systematic Reviews and Meta-Analyses, PRISMA, en inglés). La búsqueda se realizó el 1er de junio de 2020. Se identificaron e incluyeron estudios ex vivo de ciencia básica y estudios biomecánicos publicados, que evaluaran la magnitud y distribución de la presión en la interfase tendón-huella de las roturas del manguito rotador reparadas entre enero de 2015 y junio de 2020. Se realizaron búsquedas sistemáticas en las bases de datos MEDLINE, Embase, Scopus y Google Scholar utilizando los términos y operadores booleanos: (Rotator Cuff OR Supraspinatus OR Infraspinatus OR Subscapularis OR Teres Minor) AND Pressure AND Footprint. En la base de datos Embase, respetando su sintaxis, se utilizó: Rotator Cuff AND Pressure AND Footprint. RESULTADOS Un total de 15 de los 87 artículos encontrados cumplieron con todos los criterios de elegibilidad y se incluyeron en el análisis. CONCLUSIÓN La presión y área de contacto sería optimizada biomecánicamente con una reparación transósea de doble fila equivalente, sin nudos en la hilera medial, y con el uso de cintas para su ejecución, conceptos de reparación específica para roturas delaminadas, y limitación de la abducción en el postoperatorio inmediato.

OBJETIVE To provide a comprehensive synopsis and analysis of biomechanical studies on the magnitude and distribution of pressure at the tendon-footprint interface of rotator cuff tears reported in the literature in the last five years. METHODS The research was performed according to the methods described in the Cochrane Manual. The results are reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) consensus. The search was performed on June 1st, 2020. We identified and included ex vivo basic science studies and published biomechanical studies that evaluated the magnitude and distribution of pressure at the tendon-footprint interface of rotator cuff tears repaired between January 2015 and June 2020. Systematic searches on the MEDLINE, Embase, Scopus and Google Scholar databases were performed using the terms and Boolean operators: (Rotator Cuff OR Supraspinatus OR Infraspinatus OR Subscapularis OR Teres Minor) AND Pressure AND Footprint. In the Embase database, respecting its syntax, the following was used: Rotator Cuff AND Pressure AND Footprint. RESULTS In total, 15 of the 87 articles found fulfilled all the eligibility criteria and were included in the analysis. CONCLUSION The pressure and contact area would be biomechanically optimized with an equivalent transosseous double-row repair, without knots in the medial row, and with the use of tapes for its execution, specific repair concepts for delaminated tears, and a limitation of abduction in the immediate postoperative period.

Impact of Preoperative Testing on Patients Undergoing Ophthalmologic Surgery: A Retrospective Cohort Study.

OBJECTIVE: Routine medical testing is not recommended before cataract surgery, but no consensus exists about preoperative testing before general ophthalmologic surgery. We aimed to assess the impact of preoperative testing on patients undergoing ophthalmologic surgery by analyzing their surgical outcomes and complications. METHODS: We retrospectively reviewed electronic health records of patients who had preoperative evaluations before cataract or noncataract ophthalmologic surgery at a tertiary care center from January 1, 2015, through December 31, 2019. RESULTS: The cohort consisted of 2268 patients (1270 [56.0%] women). The most frequent ophthalmologic procedure was cataract extraction (n = 1450 [63.9%]). Laboratory tests results were available for 489 patients (33.7%) in the cataract group; of these, 275 results (56.2%) had abnormal values, and 18 patients (6.5%) required preoperative interventions. Preoperative test results were available for 772 out of 818 patients (94.4%) having noncataract procedures. Of these, 384 results (49.7%) had abnormal values, and 10 patients (2.6%) required additional intervention. No significant differences were observed for the rate of surgery cancellations between the cataract and noncataract patient groups (0.6% vs 1.0%; P = .24). Of the 12 patients (0.5%) who had complications, all had undergone preoperative testing. CONCLUSIONS: No differences in outcomes and complications were observed among patients who underwent cataract or noncataract surgery. It is reasonable to consider avoiding preoperative testing in patients undergoing ophthalmologic surgery.

The assessment of cognitive and behavioural disturbances in vascular cognitive impairment (VCI) - recommendations of an expert working group.

With newer research-based classification systems, the term Vascular Cognitive Impairment (VCI) is now preferred to vascular dementia. VCI is an umbrella term that includes all forms of cognitive deficits ranging from mild cognitive impairment of vascular origin (VaMCI) to vascular dementia (VaD). The new VCI construct takes into account the fact that in addition to single strategic infarcts, multiple infarcts, and leukoaraiosis, there are other mechanisms of cerebrovascular disease such as chronic hypoperfusion that might account for the pattern of cognitive deficits associated with vascular dementia. The key to defining the spectrum of VCI is neuropsychological testing, bedside or office-based clinical examination, and neuroimaging. The lack of specific cognitive tools that are sufficiently sensitive to detect subtle deficits makes the assessment of cognitive impairment difficult. Prospective cross-sectional and longitudinal studies of VCI from different settings are therefore required. Although there have been few published reports, behavioural and psychological symptoms (BPS) are inherently present in VCI from the onset and during the course of the disease. Besides the type of population (i.e. clinical, community or nursing-home settings), the definition of VCI/VaD and the instruments used, and differences in the prevalence and pattern of BPS between various studies, could be due to other, often unconsidered, factors such as gender, age, education, use of medication and VCI/VaD severity.

Nascent RNA antagonizes the interaction of a set of regulatory proteins with chromatin.

A number of regulatory factors are recruited to chromatin by specialized RNAs. Whether RNA has a more general role in regulating the interaction of proteins with chromatin has not been determined. We used proteomics methods to measure the global impact of nascent RNA on chromatin in embryonic stem cells. Surprisingly, we found that nascent RNA primarily antagonized the interaction of chromatin modifiers and transcriptional regulators with chromatin. Transcriptional inhibition and RNA degradation induced recruitment of a set of transcriptional regulators, chromatin modifiers, nucleosome remodelers, and regulators of higher-order structure. RNA directly bound to factors, including BAF, NuRD, EHMT1, and INO80 and inhibited their interaction with nucleosomes. The transcriptional elongation factor P-TEFb directly bound pre-mRNA, and its recruitment to chromatin upon Pol II inhibition was regulated by the 7SK ribonucleoprotein complex. We postulate that by antagonizing the interaction of regulatory proteins with chromatin, nascent RNA links transcriptional output with chromatin composition.

Early Cerebral Hypoperfusion in Patients with Orthostatic Intolerance Without Tachycardia During Head-Up Tilt Test is Independent of Vasovagal Response.

BACKGROUND: Cerebral hypoperfusion before syncope has been shown in patients with chronic orthostatic intolerance (OI) without tachycardia, but it is unknown if an initial decrease of cerebral blood flow velocity (CBFv) could be related to the vasovagal response (VVR) to head-up tilt test (HUTT). OBJECTIVE: The objective of the study was to compare cardiovascular, cerebrovascular, and autonomic variables during HUTT in OI patients with or without a VVR. METHODS: We included 74 subjects (58% female, mean age 33 ± 12 years) who underwent a 30-min HUTT and were divided into three groups: OI with VVR positive (VVR+), OI without VVR negative (VVR-), and asymptomatic healthy subjects with negative HUTT (control group). Cardiovascular, cerebrovascular, and autonomic variables were assessed beat-to-beat during HUTT with a Task Force monitor and a trans-cranial Doppler. Mean values were evaluated at baseline and throughout the first 10 min of tilting. RESULTS: Cardiovascular variables were similar in the three groups. Systolic, diastolic, and mean CBFv were similar in VVR+ and VVR-, but both groups had lower CBFv than the control group. Systolic and diastolic CBFv decreased from baseline since min 1 in VVR+ and VVR- and since min 5 in the control group. The mean CBFv had a significant decrease since min 1 compared to baseline in all groups. Spectral indices of heart rate and blood pressure variability showed a similar autonomic response to HUTT in all groups. CONCLUSION: Patients with chronic OI without tachycardia have early postural cerebral hypoperfusion, regardless of the VVR during HUTT.

Transient Orthostatic Hypertension During Head-Up Tilt Test in Young Adults: A Phenotype of Blood Pressure Variability.

PURPOSE: The mechanisms underlying orthostatic hypertension (OHT) remain poorly understood. The authors evaluated the cardiovascular, cerebrovascular dynamics, and autonomic response to head-up tilt test (HUTT) in young adults with symptoms of orthostatic intolerance and transient OHT. METHODS: Forty-four female subjects were included (34 ± 13 years old) and categorized in three groups after a 30-minute 70° passive HUTT: symptomatic patients with OHT (surge of systolic blood pressure ≥20 mm Hg for at least 5 minutes at any given time during HUTT), orthostatic intolerance (symptomatic patients without orthostatic blood pressure changes), and healthy asymptomatic control subjects. RESULTS: At baseline, OHT patients had lower systolic blood pressure than orthostatic intolerance patients (103 ± 8 vs. 116 ± 10 mm Hg, p < 0.01) and lower baroreflex sensitivity than control subjects (15.8 ± 8.3 vs. 27.1 ± 11.7 ms/mm Hg, p = 0.01). On tilt, cardiac output decreased in OHT patients from 6.1 ± 1.4 L/minute during baseline to 5.2 ± 0.8 L/minute after 10 minutes of HUTT (p = 0.01). In OHT patients at 30 minutes of HUTT, sympathetic efferent heart activity was higher (77.4 ± 14.9 normalized units or nu) than orthostatic intolerant patients (63.5 ± 11.8 nu, p = 0.02) and control subjects (65.8 ± 11.2 nu, p = 0.05). Cerebrovascular resistance in OHT was higher than control subjects after 30 minutes (2.2 ± 0.8 vs. 1.6 ± 0.3 cm/second, respectively, p = 0.02). CONCLUSIONS: This study demonstrates that transient OHT can occur at any given time during HUTT. These patients exhibit a decrease in cardiac output and a hyperadrenergic response to tilt.