Two novel WTX mutations underscore the unpredictability of male survival in osteopathia striata with cranial sclerosis

Perdu B, Lakeman P, Mortier G, Koenig R, Lachmeijer AMA, Van Hul W. Two novel WTX mutations underscore the unpredictability of male survival in osteopathia striata with cranial sclerosis. Osteopathia striata with cranial sclerosis (OMIM ##300373) is an X‐linked dominant sclerosing bone dysplasia that presents in females with macrocephaly, cleft palate, mild learning disabilities, sclerosis of the long bones and skull, and longitudinal striations visible on radiographs of the long bones, pelvis, and scapulae. In males this entity is usually associated with foetal or neonatal lethality, because of severe heart defects and/or gastrointestinal malformations, and is often accompanied by bilateral fibula aplasia. Recently, the disease‐causing gene was identified as the WTX gene (FAM123B). Initially it was suggested that the mutations in the 5′ region of the WTX gene are associated with male lethality. Mutation analysis in individuals of two families diagnosed with OSCS revealed two novel WTX mutations. In one family, the affected male is still alive in his teens. These mutations underline the unpredictability of male survival and suggest that WTX mutations should be considered in cases of male cranial sclerosis, even if striations are not present. An overview of all known mutations and their associated characteristics provide a valuable resource for the molecular analysis of OSCS.     

Gender differences in clinical presentation and management of patients with acute coronary syndrome in Southwest of Saudi Arabia

Objective

Gender differences in the clinical presentation and management of patients with acute coronary syndrome (ACS) have been reported in different parts of the world with contradicting results. We aimed at investigating the presence of gender bias in patients admitted with ACS to Aseer Central Hospital (ACH).

Methods

A retrospective cohort of all consecutive patients admitted to ACH with the diagnosis of ACS, during the period between the 1st of June 2007 and the 31st of May 2009 was studied. Data on demographic and clinical profiles, management and outcomes of ACS patients were collected and compared for both genders.

Results

The present study included 148 females and 397 males. Females were significantly older than males (62.9 ± 14.2 vs. 60 ± 13.4, respectively, P < 0.03), were less likely ever to have smoked (0.7% vs. 26.2%, respectively, P < 0.001), less likely to have had a history of hyperlipidemia (10.8% vs. 22.2%, respectively, P < 0.003) or family history of ischemic heart disease (10.1% vs. 18.9%, respectively, P < 0.014). Female patients presented more with atypical presentation (42.6% vs. 28.9%, respectively, P < 0.003), more with unstable angina (72.3% vs. 50.4%, respectively, P < 0.001), and less with ST-elevation myocardial infarction (18.9% vs. 40.8%, respectively, P < 0.001). Furthermore, they had significantly lower levels of hemoglobin compared to males (12.9 ± 2.3 vs. 14.5 ± 2.2 g/L, respectively, P < 0.001), and higher levels of high density lipoprotein (1.1 ± 0.4 vs. 0.98 ± 0.4 mmol/L, respectively, P < 0.008). Left ventricular ejection fraction was significantly higher in female patients compared to males (50.9 ± 14 vs. 45.8 ± 14, respectively, P < 0.003). Coronary angiography showed a higher rate of normal findings (29.3% vs. 8.9%, respectively, P < 0.001) and less severe disease (46.7% vs. 60.3%, respectively, P < 0.027) in women, however, they were less likely to undergo invasive revascularization procedures (31% vs. 42.8%, respectively, P < 0.013). No significant differences were found between both sexes regarding in-hospital mortality or re-infarction rates.

Conclusion

We documented gender differences in both clinical presentation as well as management of patients admitted with ACS to ACH. However, there were no significant differences between both genders regarding the clinical in-hospital outcomes. Emphasis should be made to avoid such bias in the future.     

Antimicrobial Resistance Among Nosocomial Isolates in a Teaching Hospital in Goa

Background:

Emergence of polyantimicrobial resistant strains of hospital pathogens has presented a challenge in the provision of good quality in-patient care. Inappropriate use of antibiotics in the hospital is largely responsible for this catastrophe. Bacteriological surveillance of the cases of nosocomial infections is crucial for framing an evidence-based antimicrobial policy for a hospital.

Materials and Methods:

A prospective study was undertaken among 498 patients from medicine and surgery wards in a tertiary teaching hospital in Goa. The patients were followed up clinico-bacteriologically for the occurrence of nosocomial infections (NI). Antibiotic susceptibility testing was done using Kirby-Bauer disc diffusion method.

Results:

The overall infection rate was 33.93 ± 4.16 infections per 100 patients. Urinary tract infection was the most common NI (26.63%), followed by surgical site infection (23.67%), wound infection (23%) and nosocomial pneumonia (18.34%). Ninety-seven percent of the isolates were bacterial, while the others were fungal. More than 80% of the NIs were caused by Gram-negative bacteria, predominantly Pseudomonas aeruginosa, Escherichia coli and Aceinetobacter baumanii. Almost 70% of the isolates were resistant to all the antibiotics for which susceptibility was tested; the rest were sensitive to amikacin, cefoperazone-sulbactam and other antibiotics including methicillin, co-trimoxazole, teicoplenin, vancomycin and rifampicin, either singly or in combination. The proportion of MRSA was 71.4%. Resistance to a particular antibiotic was found to be directly proportional to the antibiotic usage in the study setting.

Conclusion:

Surveillance of nosocomial infections with emphasis on the microbiologic surveillance and frequent antimicrobial audit are critical towards curbing the evil of polyantimicrobial resistant nosocomial infections in a hospital.     

Effect of menopause and hormone replacement therapy on urinary excretion of pyridinium cross-links: a longitudinal and cross-sectional study

OBJECTIVE: To study longitudinally the effect of the menopause and hormone replacement therapy on the new markers of bone resorption: urinary excretion of pyridinoline and deoxypyridinoline. DESIGN AND PATIENTS: Urinary pyridinoline and deoxypyridinoline were measured every 3 months for 2-3 years in 15 healthy women aged 45-54 years. Nine remained premenopausal and six became post-menopausal during the study. Urinary pyridinoline and deoxypyridinoline were also measured before and after 3 months of either placebo or hormone replacement therapy in 65 post-menopausal women, aged 45-54 years, who were participating in a double-blind study. MEASUREMENTS: Urinary pyridinoline and deoxypyridinoline were measured in fasting urine samples by spectrofluorometry after high performance liquid chromatography and corrected for creatinine excretion. RESULTS: Urinary pyridinoline and deoxypyridinoline remained almost constant during the premenopausal period. Both started to increase 6 months after the last menstrual bleeding and the mean post-menopausal values were 30-50% higher than the premenopausal values in the same subjects (values in nmol/mmol creatinine given as mean +/- SEM: urinary pyridinoline (premenopausal) = 29 +/- 2 vs urinary pyridinoline (post-menopausal) = 38 +/- 6, P < 0.05; urinary deoxypyridinoline (premenopausal) = 8 +/- 1 vs urinary deoxypyridinoline (post-menopausal) = 12 +/- 1, P < 0.05). Three months of post-menopausal hormone replacement therapy decreased (P < 0.001) both to premenopausal levels. CONCLUSION: Urinary pyridinoline and deoxypyridinoline, new markers of bone resorption, remain fairly constant in the years before the menopause and start to increase about 6 months after the last menstrual bleeding. This increase is reversed by hormone replacement therapy.     

A prospective international observational prevalence study on prone positioning of ARDS patients: the APRONET (ARDS Prone Position Network) study

Introduction

While prone positioning (PP) has been shown to improve patient survival in moderate to severe acute respiratory distress syndrome (ARDS) patients, the rate of application of PP in clinical practice still appears low.

Aim

This study aimed to determine the prevalence of use of PP in ARDS patients (primary endpoint), the physiological effects of PP, and the reasons for not using it (secondary endpoints).

Methods

The APRONET study was a prospective international 1-day prevalence study performed four times in April, July, and October 2016 and January 2017. On each study day, investigators in each ICU had to screen every patient. For patients with ARDS, use of PP, gas exchange, ventilator settings and plateau pressure (Pplat) were recorded before and at the end of the PP session. Complications of PP and reasons for not using PP were also documented. Values are presented as median (1st–3rd quartiles).

Results

Over the study period, 6723 patients were screened in 141 ICUs from 20 countries (77% of the ICUs were European), of whom 735 had ARDS and were analyzed. Overall 101 ARDS patients had at least one session of PP (13.7%), with no differences among the 4 study days. The rate of PP use was 5.9% (11/187), 10.3% (41/399) and 32.9% (49/149) in mild, moderate and severe ARDS, respectively (P = 0.0001). The duration of the first PP session was 18 (16–23) hours. Measured with the patient in the supine position before and at the end of the first PP session, PaO₂/F_IO₂ increased from 101 (76–136) to 171 (118–220) mmHg (P = 0.0001) driving pressure decreased from 14 [11–17] to 13 [10–16] cmH₂O (P = 0.001), and Pplat decreased from 26 [23–29] to 25 [23–28] cmH₂O (P = 0.04). The most prevalent reason for not using PP (64.3%) was that hypoxemia was not considered sufficiently severe. Complications were reported in 12 patients (11.9%) in whom PP was used (pressure sores in five, hypoxemia in two, endotracheal tube-related in two ocular in two, and a transient increase in intracranial pressure in one).

Conclusions

In conclusion, this prospective international prevalence study found that PP was used in 32.9% of patients with severe ARDS, and was associated with low complication rates, significant increase in oxygenation and a significant decrease in driving pressure.