Effect of corticosteroid injection for trochanter pain syndrome: design of a randomised clinical trial in general practice

Background. Regional pain in the hip in adults is a common cause of a general practitioner visit. A considerable part of patients suffer from (greater) trochanteric pain syndrome or trochanteric bursitis. Local corticosteroid injections is one of the treatment options. Although clear evidence is lacking, small observational studies suggest that this treatment is effective in the short-term follow-up. So far, there are no randomised controlled trials available evaluating the efficacy of injection therapy. This study will investigate the efficacy of local corticosteroid injections in the trochanter syndrome in the general practice, using a randomised controlled trial design. The cost effectiveness of the corticosteroid injectio

Effects of chemotherapy on contralateral breast cancer risk in BRCA1 and BRCA2 mutation carriers:A nationwide cohort study

AIM: BRCA1/2 mutation carriers with primary breast cancer (PBC) are at high risk of contralateral breast cancer (CBC). In a nationwide cohort, we investigated the effects of chemotherapeutic agents given for PBC on CBC risk separately in BRCA1 and BRCA2 mutation carriers. PATIENTS AND METHODS: BRCA1 or BRCA2 mutation carriers with an invasive PBC diagnosis from 1990 to 2017 were selected from a Dutch cohort. We estimated cumulative CBC incidence using competing risks analysis. Hazard ratios (HR) for the effect of neo-adjuvant or adjuvant chemotherapy and different chemotherapeutic agents on CBC risk were estimated using Cox regression. RESULTS: We included 1090 BRCA1 and 568 BRCA2 mutation carriers; median follow-up was 8.9 and 8.4 years, respectively. Ten-year cumulative CBC incidence for treatment with and without chemotherapy was 6.7% [95%CI: 5.1–8.6] and 16.7% [95%CI: 10.8–23.7] in BRCA1 and 4.8% [95%CI: 2.7–7.8] and 16.0% [95%CI: 9.3–24.4] in BRCA2 mutation carriers, respectively. Chemotherapy was associated with reduced CBC risk in BRCA1 (multivariable HR: 0.46, 95%CI: 0.29–0.74); a similar trend was observed in BRCA2 mutation carriers (HR: 0.63, 95%CI: 0.29–1.39). In BRCA1, risk reduction was most pronounced in the first 5 years (HR: 0.32, 95%CI: 0.17–0.61). Anthracyclines and the combination of anthracyclines with taxanes were associated with substantial CBC risk reduction in BRCA1 carriers (HR: 0.34, 95%CI: 0.17–0.68 and HR: 0.22, 95%CI: 0.08–0.62, respectively). CONCLUSION: Risk-reducing effects of chemotherapy are substantial for at least 5 years and may be used in personalised CBC risk prediction in any case for BRCA1 mutation carriers

FGF receptor genes and breast cancer susceptibility: results from the Breast Cancer Association Consortium

Background:Breast cancer is one of the most common malignancies in women. Genome-wide association studies have identified FGFR2 as a breast cancer susceptibility gene. Common variation in other fibroblast growth factor (FGF) receptors might also modify risk. We tested this hypothesis by studying genotyped single-nucleotide polymorphisms (SNPs) and imputed SNPs in FGFR1, FGFR3, FGFR4 and FGFRL1 in the Breast Cancer Association Consortium. Methods:Data were combined from 49 studies, including 53 835 cases and 50 156 controls, of which 89 050 (46 450 cases and 42 600 controls) were of European ancestry, 12 893 (6269 cases and 6624 controls) of Asian and 2048 (1116 cases and 932 controls) of African ancestry. Associations with risk of breast cancer, overall and by disease sub-type, were assessed using unconditional logistic regression. Results:Little evidence of association with breast cancer risk was observed for SNPs in the FGF receptor genes. The strongest evidence in European women was for rs743682 in FGFR3; the estimated per-allele odds ratio was 1.05 (95 confidence interval=1.02-1.09, P=0.0020), which is substantially lower than that observed for SNPs in FGFR2. Conclusion:Our results suggest that common variants in the other FGF receptors are not associated with risk of breast cancer to the degree observed for FGFR2. © 2014 Cancer Research UK

Модификации арефлюксного холедохоеюноанастомоза с восстановлением пассажа желчи в двенадцатиперстную кишку

Разработаны модификации формирования холедохоеюноанастомоза, способствующие восстановлению желчетока с пассажем желчи в двенадцатиперстную кишку, что предупреждает развитие в ней пептической язвы. Предложена специальная методика мобилизации отключенного по Ру сегмента тощей кишки, обеспечивающая его полноценную моторику.Modifications of forming choledochoanastomosis promoting restoration of bile passage to the duodenum, which prevented development of peptic ulcer, were worked out. A special technique for mobilization of the switched off segment of the jejunum according to Roux promoting an adequate motility was suggested

Spectrum and antibiotic sensitivity of bacteria contaminating the upper gut in patients with malabsorption syndrome from the tropics

BACKGROUND: Various causes of malabsorption syndrome (MAS) are associated with intestinal stasis that may cause small intestinal bacterial overgrowth (SIBO). Frequency, nature and antibiotic sensitivity of SIBO in patients with MAS are not well understood. METHODS: Jejunal aspirates of 50 consecutive patients with MAS were cultured for bacteria and colony counts and antibiotic sensitivity were performed. Twelve patients with irritable bowel syndrome were studied as controls. RESULTS: Culture revealed growth of bacteria in 34/50 (68%) patients with MAS and 3/12 controls (p < 0.05). Colony counts ranged from 3 × 10(2 )to 10(15 )(median 10(5)) in MAS and 100 to 1000 (median 700) CFU/ml in controls (p 0.003). 21/50 (42%) patients had counts ≥10(5 )CFU/ml in MAS and none of controls (p < 0.05). Aerobes were isolated in 34/34 and anaerobe in 1/34. Commonest Gram positive and negative bacteria were Streptococcus species and Escherichia coli respectively. The isolated bacteria were more often sensitive to quinolones than to tetracycline (ciprofloxacin: 39/47 and norfloxacin: 34/47 vs. tetracycline 19/47, <0.01), ampicillin, erythromycin and co-trimoxazole (21/44, 14/22 and 24/47 respectively vs. tetracycline, p = ns). CONCLUSIONS: SIBO is common in patients with MAS due to various causes and quinolones may be the preferred treatment. This needs to be proved further by a randomized controlled trial

A Single-Lumen Central Venous Catheter for Continuous and Direct Intra-abdominal Pressure Measurement

Background: Abdominal compartment syndrome (ACS) is associated with high morbidity and mortality rates. Therefore, the need for a good diagnostic tool to predict intra-abdominal hypertension (IAH) and progression to ACS is paramount. Bladder pressure (BP) has been used for several years for intra-abdominal pressure (IAP) measurement but has the disadvantage that it is not a continuous measurement. In this study, a single-lumen central venous catheter (CVC) is placed through the abdominal wall into the abdominal cavity to continuously and directly monitor the intra-abdominal pressure (CDIAP). The aim of this study was to evaluate the use of CDIAP to measure BP as a representative of the true IAP. Methods: Both BP and CDIAP were prospectively recorded on a variety of surgical patients admitted to the intensive care unit (ICU) from March 2003 up to December 2004. At the end of the surgical procedure, the CVC was placed through the abdominal wall and connected to a pressure transducer. In addition, the BP was measured through the urine drainage port after clamping the catheter and filling the bladder with 50 ml of 0.9% saline. At least three paired measurements (BP and CDIAP) were performed for at least one day on the ICU in a standardized manner at preset time intervals on each patient. The paired measurements were compared using the Bland-Altman (B-A) method. Data are presented as mean ± standard deviation. Results: Over a period of 22 months (March 2003 until December 2004), 125 paired measurements of both BP and CDIAP were recorded on 25 patients. The mean age was 72.4 ± 6.6 years. Eighteen patients underwent central vascular surgery, and seven patients with peritonitis received laparotomy. The mean CDIAP was 11.4 ± 4.8 (range 2-30) mmHg, and the BP was 12.9 ± 5.3 (range 3-37) mmHg. The mean difference between CDIAP and BP was 1.6 ± 2.7 mmHg. There was an acceptable level of agreement (intraclass correlation 0.82) between IAP measured by BP and IAP measured via CDIAP. Conclusion: Continuous direct intra-abdominal pressure measurement proved that the BP measurement approach of Kron is representative of the IAP. CDIAP measurement is accurate and makes it easier for the nursing staff to be informed of the IAP

Virulence Characteristics and Genetic Affinities of Multiple Drug Resistant Uropathogenic Escherichia coli from a Semi Urban Locality in India

Extraintestinal pathogenic Escherichia coli (ExPEC) are of significant health concern. The emergence of drug resistant E. coli with high virulence potential is alarming. Lack of sufficient data on transmission dynamics, virulence spectrum and antimicrobial resistance of certain pathogens such as the uropathogenic E. coli (UPEC) from countries with high infection burden, such as India, hinders the infection control and management efforts. In this study, we extensively genotyped and phenotyped a collection of 150 UPEC obtained from patients belonging to a semi-urban, industrialized setting near Pune, India. The isolates representing different clinical categories were analyzed in comparison with 50 commensal E. coli isolates from India as well as 50 ExPEC strains from Germany. Virulent strains were identified based on hemolysis, haemagglutination, cell surface hydrophobicity, serum bactericidal activity as well as with the help of O serotyping. We generated antimicrobial resistance profiles for all the clinical isolates and carried out phylogenetic analysis based on repetitive extragenic palindromic (rep)-PCR. E. coli from urinary tract infection cases expressed higher percentages of type I (45%) and P fimbriae (40%) when compared to fecal isolates (25% and 8% respectively). Hemolytic group comprised of 60% of UPEC and only 2% of E. coli from feces. Additionally, we found that serum resistance and cell surface hydrophobicity were not significantly (p = 0.16/p = 0.51) associated with UPEC from clinical cases. Moreover, clinical isolates exhibited highest resistance against amoxicillin (67.3%) and least against nitrofurantoin (57.3%). We also observed that 31.3% of UPEC were extended-spectrum beta-lactamase (ESBL) producers belonging to serotype O25, of which four were also positive for O25b subgroup that is linked to B2-O25b-ST131-CTX-M-15 virulent/multiresistant type. Furthermore, isolates from India and Germany (as well as global sources) were found to be genetically distinct with no evidence to espouse expansion of E. coli from India to the west or vice-versa

Long-Term Morbidity and Health After Early Menopause Due to Oophorectomy in Women at Increased Risk of Ovarian Cancer:Protocol for a Nationwide Cross-Sectional Study With Prospective Follow-Up (HARMOny Study)

Background: BRCA1/2 mutation carriers are recommended to undergo risk-reducing salpingo-oophorectomy (RRSO) at 35 to 45 years of age. RRSO substantially decreases ovarian cancer risk, but at the cost of immediate menopause. Knowledge about the potential adverse effects of premenopausal RRSO, such as increased risk of cardiovascular disease, osteoporosis, cognitive dysfunction, and reduced health-related quality of life (HRQoL), is limited. Objective: The aim of this study is to assess the long-term health effects of premenopausal RRSO on cardiovascular disease, bone health, cognitive functioning, urological complaints, sexual functioning, and HRQoL in women with high familial risk of breast or ovarian cancer. Methods: We will conduct a multicenter cross-sectional study with prospective follow-up, nested in a nationwide cohort of women at high familial risk of breast or ovarian cancer. A total of 500 women who have undergone RRSO before 45 years of age, with a follow-up period of at least 10 years, will be compared with 250 women (frequency matched on current age) who have not undergone RRSO or who have undergone RRSO at over 55 years of age. Participants will complete an online questionnaire on lifestyle, medical history, cardiovascular risk factors, osteoporosis, cognitive function, urological complaints, and HRQoL. A full cardiovascular assessment and assessment of bone mineral density will be performed. Blood samples will be obtained for marker analysis. Cognitive functioning will be assessed objectively with an online neuropsychological test battery. Results: This study was approved by the institutional review board in July 2018. In February 2019, we included our first participant. As of November 2020, we had enrolled 364 participants in our study. Conclusions: Knowledge from this study will contribute to counseling women with a high familial risk of breast/ovarian cancer about the long-term health effects of premenopausal RRSO. The results can also be used to offer health recommendations after RRSO

Differential overexpression of SERPINA3 in human prion diseases

Prion diseases are fatal neurodegenerative disorders with sporadic, genetic or acquired etiologies. The molecular alterations leading to the onset and the spreading of these diseases are still unknown. In a previous work we identified a five-gene signature able to distinguish intracranially BSE-infected macaques from healthy ones, with SERPINA3 showing the most prominent dysregulation. We analyzed 128 suitable frontal cortex samples, from prion-affected patients (variant Creutzfeldt-Jakob disease (vCJD) n = 20, iatrogenic CJD (iCJD) n = 11, sporadic CJD (sCJD) n = 23, familial CJD (gCJD) n = 17, fatal familial insomnia (FFI) n = 9, Gerstmann-Sträussler-Scheinker syndrome (GSS)) n = 4), patients with Alzheimer disease (AD, n = 14) and age-matched controls (n = 30). Real Time-quantitative PCR was performed for SERPINA3 transcript, and ACTB, RPL19, GAPDH and B2M were used as reference genes. We report SERPINA3 to be strongly up-regulated in the brain of all human prion diseases, with only a mild up-regulation in AD. We show that this striking up-regulation, both at the mRNA and at the protein level, is present in all types of human prion diseases analyzed, although to a different extent for each specific disorder. Our data suggest that SERPINA3 may be involved in the pathogenesis and the progression of prion diseases, representing a valid tool for distinguishing different forms of these disorders in humans

Retro-trochanteric sciatica-like pain: current concept

The aim of this manuscript is to review the current knowledge in terms of retro-trochanteric pain syndrome, make recommendations for diagnosis and differential diagnosis and offer suggestions for treatment options. The terminology in the literature is confusing and these symptoms can be referred to as ‘greater trochanteric pain syndrome’, ‘trochanteric bursitis’ and ‘trochanteritis’, among other denominations. The authors focus on a special type of sciatica, i.e. retro-trochanteric pain radiating down to the lower extremity. The impact of different radiographic assessments is discussed. The authors recommend excluding pathology in the spine and pelvic area before following their suggested treatment algorithm for sciatica-like retro-trochanteric pain. Level of evidence II