Unexpected Diagnosis of Complete Androgen Insensitivity Syndrome (CAIS) During Inguinal Hernia Repair in 11-year-old-girl

Complete Androgen Insensitivity Syndrome (CAIS) is an X-link recessive genetic mutation of androgen receptor (AR) gene leading to complete inability of cell to respond to the androgens. CAIS occurs in 1 out of 20,400 XY live-birth babies, and affects about 1–2% of prepubertal girls that present with an inguinal hernia. Although individuals with CAIS have XY, those with grades 6 and 7 on the Quigley scale are born phenotypically female, without any signs of genital masculinization. Thus, individuals affected by CAIS develop a normal external female phenotype with normal female external genitalia, well-developed breast, absent uterus, and bilateral undescended testicles. The question of CAIS diagnosis does not come forward until the absent menses at the puberty is noted or accidentally during an inguinal hernia repair in a premenarchal girl. The present study reports a case of inguinal hernia repair on 11-year-old girl, which led to unexpected intraoperative notion of CAIS. The diagnostic work-up, genetic counseling, sex assignment, and the need for preoperative CAIS screening in girls with bilateral inguinal hernia are described and discussed. Keywords: DSD, CAIS, bilateral inguinal hernia, gonadectom

Accuracy of non-invasive cuffless blood pressure in the intensive care unit: Promises and challenges

ObjectiveContinuous non-invasive cuffless blood pressure (BP) monitoring may reduce adverse outcomes in hospitalized patients if accuracy is approved. We aimed to investigate accuracy of two different BP prediction models in critically ill intensive care unit (ICU) patients, using a prototype cuffless BP device based on electrocardiogram and photoplethysmography signals. We compared a pulse arrival time (PAT)-based BP model (generalized PAT-based model) derived from a general population cohort to more complex and individualized models (complex individualized models) utilizing other features of the BP sensor signals.MethodsPatients admitted to an ICU with indication of invasive BP monitoring were included. The first half of each patient’s data was used to train a subject-specific machine learning model (complex individualized models). The second half was used to estimate BP and test accuracy of both the generalized PAT-based model and the complex individualized models. A total of 7,327 measurements of 15 s epochs were included in pairwise comparisons across 25 patients.ResultsThe generalized PAT-based model achieved a mean absolute error (SD of errors) of 7.6 (7.2) mmHg, 3.3 (3.1) mmHg and 4.6 (4.4) mmHg for systolic BP, diastolic BP and mean arterial pressure (MAP) respectively. Corresponding results for the complex individualized model were 6.5 (6.7) mmHg, 3.1 (3.0) mmHg and 4.0 (4.0) mmHg. Percentage of absolute errors within 10 mmHg for the generalized model were 77.6, 96.2, and 89.6% for systolic BP, diastolic BP and MAP, respectively. Corresponding results for the individualized model were 83.8, 96.2, and 94.2%. Accuracy was significantly improved when comparing the complex individualized models to the generalized PAT-based model in systolic BP and MAP, but not diastolic BP.ConclusionA generalized PAT-based model, developed from a different population was not able to accurately track BP changes in critically ill ICU patients. Individually fitted models utilizing other cuffless BP sensor signals significantly improved accuracy, indicating that cuffless BP can be measured non-invasively, but the challenge toward generalizable models remains for future research to resolve

Rare Suprasellar Chordoid Meningioma with INI1 Gene Mutation

Background: Chordoid Meningioma is a rare brain tumour characterized genetically by loss of genetic material from chromosome 22q at cytogenetic level resulting in mutation of NF2 gene. Objectives and case report: In the present report, we described a rare case of suprasellar chordoid meningioma, which presented in a 32-year-old-woman. Her only complain was throbbing headache. Neurological examination showed left temporal hemianopia, decreased visual acuity (3/6), and no physical abnormalities related to Castleman syndrome were noted. Cranial magnetic resonance (MR) images demonstrated a 28x15 mm mass in the sellar region, which showed iso-to low intensity that enhanced vividly after gadolinium with upwards displacement of the Optic chiasm. Total surgical excision of the tumour was performed and subsequent histological examination of the tumour showed typical histology pattern of chordoid meningioma grade II according to the WHO classification system of meningiomas. Genomic DNA was extracted and mutation analysis for INI1 gene using primer of exon 4, 5, 7, and 9 showed mutation involving exon 9. DNA sequencing showedheterozygosity C­­­­­­­­­­­­­­­­­­-T mutation in exon 9 of INI1 gene leading to change of amino acid serine to phenylalanine at (codon 63). The details of this case are presented with a review of the literature

Detection of Nonadherence to Antihypertensive Treatment by Measurements of Serum Drug Concentrations

Nonadherence to drugs is a challenge in hypertension treatment. We aimed to assess the prevalence of nonadherence by serum drug concentrations compared with 2 indirect methods and relate to the prescribed drug regimens in a nationwide multicenter study. Five hundred fifty patients with hypertension using ≥2 antihypertensive agents participated. We measured concentrations of 23 antihypertensive drugs using ultra high performance liquid chromatography tandem mass-spectrometry and compared with patients’ self-reports and investigators’ assessment based on structured interview. We identified 40 nonadherent patients (7.3%) using serum drug concentrations. They had higher office diastolic blood pressure (90 versus 83 mm Hg, P<0.01) and daytime diastolic blood pressure (85 versus 80 mm Hg, P<0.01) though systolic blood pressures did not differ significantly. They had more prescribed daily antihypertensive pills (2.5 versus 2.1 pills, P<0.01) and total daily pills (5.5 versus 4.4 pills, P=0.03). Prescription of fixed-dose combination pills were lower among the nonadherent patients identified by serum concentrations (45.0 versus 67.1%, P<0.01). Fifty-three patients self-reported nonadherence, while the investigators suspected 69 nonadherent patients. These groups showed no or few differences in drug regimens, respectively. In summary, we detected 7.3% prevalence of nonadherence by serum drug measurements in patients using ≥2 antihypertensive agents in a nationwide study; they had higher office and ambulatory diastolic blood pressures, higher number of prescribed daily pills, more daily antihypertensive pills, and less frequent prescriptions of fixed-dose combination pills. Indirect methods showed poor overlap with serum drugs concentrations and no or minimal medication differences. Thus, serum measurements of drugs were useful in detection and characterization of nonadherence to antihypertensive treatment.acceptedVersio

Blood pressure response to renal denervation is correlated with baseline blood pressure variability: a patient-level meta-analysis

Background: Sympathetic tone is one of the main determinants of blood pressure (BP) variability and treatment-resistant hypertension. The aim of our study was to assess changes in BP variability after renal denervation (RDN). In addition, on an exploratory basis, we investigated whether baseline BP variability predicted the BP changes after RDN. Methods: We analyzed 24-h BP recordings obtained at baseline and 6 months after RDN in 167 treatmentresistant hypertension patients (40% women; age, 56.7 years; mean 24-h BP, 152/90 mmHg) recruited at 11 expert centers. BP variability was assessed by weighted SD [SD over time weighted for the time interval between consecutive readings (SDiw)], average real variability (ARV), coefficient of variation, and variability independent of the mean (VIM). Results: Mean office and 24-h BP fell by 15.4/6.6 and 5.5/ 3.7 mmHg, respectively (P &lt; 0.001). In multivariable-adjusted analyses, systolic/diastolic SDiw and VIM for 24-h SBP/DBP decreased by 1.18/0.63 mmHg (P 0.01) and 0.86/0.42 mmHg (P 0.05), respectively, whereas no significant changes in ARV or coefficient of variation occurred. Furthermore, baseline SDiw (P ¼ 0.0006), ARV (P ¼ 0.01), and VIM (P ¼ 0.04) predicted the decrease in 24-h DBP but not 24-h SBP after RDN. Conclusion: RDN was associated with a decrease in BP variability independent of the BP level, suggesting that responders may derive benefits from the reduction in BP variability as well. Furthermore, baseline DBP variability estimates significantly correlated with mean DBP decrease after RDN. If confirmed in younger patients with less arterial damage, in the absence of the confounding effect of drugs and drug adherence, baseline BP variability may prove a good predictor of BP response to RDN

Recurrent and multiple bladder tumors show conserved expression profiles

<p>Abstract</p> <p>Background</p> <p>Urothelial carcinomas originate from the epithelial cells of the inner lining of the bladder and may appear as single or as multiple synchronous tumors. Patients with urothelial carcinomas frequently show recurrences after treatment making follow-up necessary. The leading hypothesis explaining the origin of meta- and synchronous tumors assumes a monoclonal origin. However, the genetic relationship among consecutive tumors has been shown to be complex in as much as the genetic evolution does not adhere to the chronological appearance of the metachronous tumors. Consequently, genetically less evolved tumors may appear chronologically later than genetically related but more evolved tumors.</p> <p>Methods</p> <p>Forty-nine meta- or synchronous urothelial tumors from 22 patients were analyzed using expression profiling, conventional CGH, LOH, and mutation analyses.</p> <p>Results</p> <p>We show by CGH that partial chromosomal losses in the initial tumors may not be present in the recurring tumors, by LOH that different haplotypes may be lost and that detected regions of LOH may be smaller in recurring tumors, and that mutations present in the initial tumor may not be present in the recurring ones. In contrast we show that despite apparent genomic differences, the recurrent and multiple bladder tumors from the same patients display remarkably similar expression profiles.</p> <p>Conclusion</p> <p>Our findings show that even though the vast majority of the analyzed meta- and synchronous tumors from the same patients are not likely to have originated directly from the preceding tumor they still show remarkably similar expressions profiles. The presented data suggests that an expression profile is established early in tumor development and that this profile is stable and maintained in recurring tumors.</p

Female genital mutilation of a karyotypic male presenting as a female with delayed puberty

BACKGROUND: Female genital mutilation (FGM) is commonly practiced mainly in a belt reaching from East to West Africa north of the equator. The practice is known across socio-economic classes and among different ethnic, religious, and cultural groups. Few studies have been appropriately designed to measure the health effects of FGM. However, the outcome of FGM on intersex individuals has never been discussed before. CASE PRESENTATION: The patient first presented as a female with delayed puberty. Hormonal analysis revealed a normal serum prolactin level of 215 Mu/L, a low FSH of 0.5 Mu/L, and a low LH of 1.1 Mu/L. Type IV FGM (Pharaonic circumcision) had been performed during childhood. Chromosomal analysis showed a 46, XY karyotype and ultrasonography verified a soft tissue structure in the position of the prostate. CONCLUSION: FGM pose a threat to the diagnosis and management of children with abnormal genital development in the Sudan and similar societies

Blood pressure changes after renal denervation at 10 European expert centers

We did a subject-level meta-analysis of the changes (Δ) in blood pressure (BP) observed 3 and 6 months after renal denervation (RDN) at 10 European centers. Recruited patients (n=109; 46.8% women; mean age 58.2 years) had essential hypertension confirmed by ambulatory BP. From baseline to 6 months, treatment score declined slightly from 4.7 to 4.4 drugs per day. Systolic/diastolic BP fell by 17.6/7.1 mm Hg for office BP, and by 5.9/3.5, 6.2/3.4, and 4.4/2.5 mm Hg for 24-h, daytime and nighttime BP (P0.03 for all). In 47 patients with 3- and 6-month ambulatory measurements, systolic BP did not change between these two time points (P0.08). Normalization was a systolic BP of &#60;140 mm Hg on office measurement or &#60;130 mm Hg on 24-h monitoring and improvement was a fall of 10 mm Hg, irrespective of measurement technique. For office BP, at 6 months, normalization, improvement or no decrease occurred in 22.9, 59.6 and 22.9% of patients, respectively; for 24-h BP, these proportions were 14.7, 31.2 and 34.9%, respectively. Higher baseline BP predicted greater BP fall at follow-up; higher baseline serum creatinine was associated with lower probability of improvement of 24-h BP (odds ratio for 20-μmol l(-1) increase, 0.60; P=0.05) and higher probability of experiencing no BP decrease (OR, 1.66; P=0.01). In conclusion, BP responses to RDN include regression-to-the-mean and remain to be consolidated in randomized trials based on ambulatory BP monitoring. For now, RDN should remain the last resort in patients in whom all other ways to control BP failed, and it must be cautiously used in patients with renal impairment

Frequencies of BCR-ABL1 fusion transcripts among Sudanese chronic myeloid leukaemia patients

The incidence of one or other rearrangement in chronic myeloid leukemia (CML) patients varies in different reported series. In this study we report the frequencies of BCR-ABL1 fusion transcript variants studied in 43 CML patients from Sudan. The study includes 46 Sudanese patients, three of which negative for the BCR-ABL1 fusion transcript. More than half of 43 positive patients showed b2a2 fusion transcript (53.5%), while (41.9%) showed b3a2 transcript and the remaining (4.6%) coexpression of b3a2/ b2a2 and b3a2/b2a2/e19a2. We detected neither coexpression of p210/p190 nor e1a2 alone. Male patients showed a tendency to express b2a2, while female tende to express b3a2 (p = 0.017). Moreover, a single nucleotide polymorphism was detected in BCR exon 13 in one out of four patients and this patient showed only b2a2 expression. In conclusion, we observed a significant correlation between sex and type of BCR-ABL1 transcript, an observation that deserves further investigation

A case of Cornelia de Lange syndrome from Sudan

BACKGROUND: Brachmann de Lange syndrome (BDLS) is a multiple congenital anomaly syndrome characterized by a distinctive facial appearance, prenatal and postnatal growth deficiency, psychomotor delay, behavioral problems, and malformations of the upper extremities. CASE PRESENTATION: Here we present for the first time a case of BDLS from Sudan, a 7-month-old female infant, who was referred as a case of malnutrition. The patient was from a Sudanese western tribe. Clinical investigation showed that the child was a classical case of BDLS, but with some additional clinical findings not previously reported including crowded ribs and tied tongue. CONCLUSION: Reporting BDLS cases of different ethnic backgrounds could add nuances to the phenotypic description of the syndrome and be helpful in diagnosis