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Single-Stage Immediate Breast Reconstruction Using Anatomical Silicone-Based Implant and The Hammock Technique of Dermal-Muscle Flap in Large and Ptotic breasts: A Multicenter Study.
No full textBACKGROUND
This study revisits the previously described technique of inverted-T skin-reducing mastectomy and dermal-muscle pocket as a single-stage breast reconstruction using anatomical implants in large and ptotic breasts. Refinements have been added to enhance the quality of implant coverage, improve aesthetic outcome, and augment the implant volume than previously described in the literature.
SUBJECTS AND METHODS
The study was performed in three centers in the UK, Egypt, and Libya. It included patients with large ptotic breasts with a breast cup size of D or larger. The areola-to-inframammary fold distance is of 8 cm or more, and a nipple-sternal notch distance is 25 cm or more. Modification of the dermal-muscle flap was made through dividing the medial and lateral ends of the de-epithelialized flap at a distance of one inch to create wings that could be sutured to the free edge of pectoralis major muscle to act as a hammock.
RESULTS
It included 42 patients, and the mean age of the patients was 44.4 years (range 28-62). The mean body mass index was 34.2 (range 24-42). The reconstruction was unilateral in 32 (76.2%) patients and bilateral in ten (23.8%) patients. The average implant volume was 498.5 CC (range 375-650). Seventeen (40.5%) patients had a symmetrizing breast reduction. The average follow-up time was 52 weeks. Major complications were noticed in four (7.7%) breasts: Three breasts had major skin necrosis and one breast had hematoma that necessitated surgical evacuation. There were no reported cases of implant extrusion. Minor complications were recorded in six (11.5%) breasts; two had wound infection, and three had minor skin necrosis.
CONCLUSION
The hammock technique of dermal-muscle flap is safe and versatile in large and ptotic breasts. It also creates a natural-looking breast with bigger implants
Impact of HIV and chronic kidney disease comorbidities on hepatitis C treatment choices, drug-drug interactions and hepatitis C cure.
No full textBackground Human immunodeficiency virus (HIV) co-infection and chronic kidney disease add challenges to hepatitis C virus treatment. Objective To conduct a comparative study of treatment choices, drug-drug interactions and clinical outcomes in hepatitis C mono-infected patients, or those with HIV or chronic kidney disease comorbidities. Setting Hepatitis C treatment centers of West Midlands England, United Kingdom. Method An observational study was conducted analyzing datasets of all hepatitis C patients that were referred to a large tertiary liver unit in the West Midlands, UK between July 2015 and January 2018. Patients aged ≥ 18 years with diagnosis of hepatitis C alone or co-infected with HIV or comorbid with chronic kidney disease were eligible. Main outcome measures The treatment choices, relevant potential drug-drug interactions and sustained virologic response 12 weeks post end of treatment were assessed. Results Out of 313 patients, 154 (49.2%) were hepatitis C mono-infected, 124 (39.6%) hepatitis C/HIV co-infected and 35 (11.2%) were hepatitis C/chronic kidney disease comorbid. There were 151 (98.1%) of hepatitis C mono-infected, 110 (88.7%) of hepatitis C/HIV and 20 (57.1%) of hepatitis C/chronic kidney disease patients treated with 1st line regimens. Significantly more patients who had co-morbidity with either HIV or chronic kidney disease were prescribed 2nd line regimens (8.1% and 37.1% respectively), compared to patients with hepatitis C mono-infection (1.9%) (P value < 0.05). Comorbid patients (12.1% of HIV and 25.8% of chronic kidney disease) were more likely to required drug-drug interactions advice (grade 5) than hepatitis C mono-infected (1.8%). Higher cure rates were observed in hepatitis C mono-infected (95.33%), hepatitis C/HIV (96.1%) compared to hepatitis C/chronic kidney disease patients (90.3%). Conclusion This study shows that treatment pathways permitting access to individual treatment adjustments in accordance with comorbidities and with consideration of drug-drug interaction in a multi-disciplinary team, provides successful outcomes in hepatitis C patients co-morbid with HIV or chronic kidney disease
Transjugular intrahepatic portosystemic stent-shunt in the management of portal hypertension.
No full textThese guidelines on transjugular intrahepatic portosystemic stent-shunt (TIPSS) in the management of portal hypertension have been commissioned by the Clinical Services and Standards Committee (CSSC) of the British Society of Gastroenterology (BSG) under the auspices of the Liver Section of the BSG. The guidelines are new and have been produced in collaboration with the British Society of Interventional Radiology (BSIR) and British Association of the Study of the Liver (BASL). The guidelines development group comprises elected members of the BSG Liver Section, representation from BASL, a nursing representative and two patient representatives. The quality of evidence and grading of recommendations was appraised using the GRADE system. These guidelines are aimed at healthcare professionals considering referring a patient for a TIPSS. They comprise the following subheadings: indications; patient selection; procedural details; complications; and research agenda. They are not designed to address: the management of the underlying liver disease; the role of TIPSS in children; or complex technical and procedural aspects of TIPSS
Association between non-malignant monoclonal gammopathy and adverse outcomes in chronic kidney disease: A cohort study.
No full textBACKGROUND
In studies including the general population, the presence of non-malignant monoclonal gammopathy (MG) can be causally associated with kidney damage and shorter survival. We assessed whether the presence of an MG is associated with a higher risk of kidney failure or death in individuals with chronic kidney disease (CKD).
METHODS AND FINDINGS
Data were used from 3 prospective cohorts of individuals with CKD (not on dialysis or with a kidney transplant): (1) Renal Impairment in Secondary Care (RIISC, Queen Elizabeth Hospital and Heartlands Hospital, Birmingham, UK, N = 878), (2) Salford Kidney Study (SKS, Salford Royal Hospital, Salford, UK, N = 861), and (3) Renal Risk in Derby (RRID, Derby, UK, N = 1,739). Participants were excluded if they had multiple myeloma or any other B cell lymphoproliferative disorder with end-organ damage. Median age was 71.0 years, 50.6% were male, median estimated glomerular filtration rate was 42.3 ml/min/1.73 m2, and median urine albumin-to-creatinine ratio was 3.4 mg/mmol. All non-malignant MG was identified in the baseline serum of participants of RIISC. Further, light chain MG (LC-MG) was identified and studied in participants of RIISC, SKS, and RRID. Participants were followed up for kidney failure (defined as the initiation of dialysis or kidney transplantation) and death. Associations with the risk of kidney failure were estimated by competing-risks regression (handling death as a competing risk), and associations with death were estimated by Cox proportional hazards regression. In total, 102 (11.6%) of the 878 RIISC participants had an MG. During a median follow-up time of 74.0 months, there were 327 kidney failure events and 202 deaths. The presence of MG was not associated with risk of kidney failure (univariable subhazard ratio [SHR] 0.97 [95% CI 0.68 to 1.38], P = 0.85; multivariable SHR 1.16 [95% CI 0.80 to 1.69], P = 0.43), and although there was a higher risk of death in univariable analysis (hazard ratio [HR] 2.13 [95% CI 1.49 to 3.02], P < 0.001), this was not significant in multivariable analysis (HR 1.37 [95% CI 0.93 to 2.00], P = 0.11). Fifty-five (1.6%) of the 3,478 participants from all 3 studies had LC-MG. During a median follow-up time of 62.5 months, 564 of the 3,478 participants progressed to kidney failure, and 803 died. LC-MG was not associated with risk of kidney failure (univariable SHR 1.07 [95% CI 0.58 to 1.96], P = 0.82; multivariable SHR 1.42 [95% CI 0.78 to 2.57], P = 0.26). There was a higher risk of death in those with LC-MG in the univariable model (HR 2.51 [95% CI 1.59 to 3.96], P < 0.001), but not in the multivariable model (HR 1.49 [95% CI 0.93 to 2.39], P = 0.10). An important limitation of this work was that only LC-MG, rather than any MG, could be identified in participants from SKS and RRID.
CONCLUSIONS
The prevalence of MG was higher in this CKD cohort than that reported in the general population. However, the presence of an MG was not independently associated with a significantly higher risk of kidney failure or, unlike in the general population, risk of death
Protocol for the EARCO Registry: a pan-European observational study in patients with α-antitrypsin deficiency.
No full textRationale and objectives
Alpha-1 antitrypsin deficiency (AATD) is a genetic condition that leads to an increased risk of emphysema and liver disease. Despite extensive investigation, there remain unanswered questions concerning the natural history, pathophysiology, genetics and the prognosis of the lung disease in association with AATD. The European Alpha-1 Clinical Research Collaboration (EARCO) is designed to bring together researchers from European countries and to create a standardised database for the follow-up of patients with AATD.
Study design and population
The EARCO Registry is a non-interventional, multicentre, pan-European, longitudinal observational cohort study enrolling patients with AATD. Data will be collected prospectively without interference/modification of patient's management by the study team. The major inclusion criterion is diagnosed severe AATD, defined by an AAT serum level <11 µM (50 mg·dL) and/or a proteinase inhibitor genotype ZZ, SZ or compound heterozygotes or homozygotes of other rare deficient variants. Assessments at baseline and during the yearly follow-up visits include lung function testing (spirometry, body plethysmography and diffusing capacity of the lung), exercise capacity, blood tests and questionnaires (symptoms, quality of life and physical activity). To ensure correct data collection, there will be designated investigator staff to document the data in the case report form. All data will be reviewed by the EARCO database manager.
Summary
The EARCO Registry aims to understand the natural history and prognosis of AATD better with the goal to create and validate prognostic tools to support medical decision-making
Retinal blood flow in critical illness and systemic disease: a review.
No full textBACKGROUND
Assessment and maintenance of end-organ perfusion are key to resuscitation in critical illness, although there are limited direct methods or proxy measures to assess cerebral perfusion. Novel non-invasive methods of monitoring microcirculation in critically ill patients offer the potential for real-time updates to improve patient outcomes.
MAIN BODY
Parallel mechanisms autoregulate retinal and cerebral microcirculation to maintain blood flow to meet metabolic demands across a range of perfusion pressures. Cerebral blood flow (CBF) is reduced and autoregulation impaired in sepsis, but current methods to image CBF do not reproducibly assess the microcirculation. Peripheral microcirculatory blood flow may be imaged in sublingual and conjunctival mucosa and is impaired in sepsis. Retinal microcirculation can be directly imaged by optical coherence tomography angiography (OCTA) during perfusion-deficit states such as sepsis, and other systemic haemodynamic disturbances such as acute coronary syndrome, and systemic inflammatory conditions such as inflammatory bowel disease.
CONCLUSION
Monitoring microcirculatory flow offers the potential to enhance monitoring in the care of critically ill patients, and imaging retinal blood flow during critical illness offers a potential biomarker for cerebral microcirculatory perfusion
Ensemble learning for poor prognosis predictions: a case study on SARS-CoV2.
No full textOBJECTIVE
Risk prediction models are widely used to inform evidence-based clinical decision making. However, few models developed from single cohorts can perform consistently well at population level where diverse prognoses exist (such as the SARS-CoV2 pandemic). This study aims at tackling this challenge by synergising prediction models from the literature using ensemble learning.
MATERIALS AND METHODS
In this study we selected and reimplemented seven prediction models for COVID-19, which were derived from diverse cohorts and used different implementation techniques. A novel ensemble learning framework was proposed to synergise them for realising personalised predictions for individual patients. Four diverse international cohorts (2 from the UK and 2 from China; total N=5,394) were used to validate all eight models on discrimination, calibration and clinical usefulness.
RESULTS
Results showed that individual prediction models could perform well on some cohorts while poorly on others. Conversely, the ensemble model achieved the best performances consistently on all metrics quantifying discrimination, calibration and clinical usefulness. Performance disparities were observed in cohorts from the two countries: all models achieved better performances on the China cohorts.
DISCUSSION
When individual models were learned from complementary cohorts, the synergised model will have the potential to achieve synergised performances. Results indicate that blood parameters and physiological measurements might have better predictive powers when collected early, which remains to be confirmed by further studies.
CONCLUSIONS
Combining a diverse set of individual prediction models, ensemble method can synergise a robust and well-performing model by choosing the most competent ones for individual patients
Blood markers in remote ischaemic conditioning for acute ischaemic stroke: data from the REmote ischaemic Conditioning After Stroke Trial.
No full textBACKGROUND
Remote ischaemic per-conditioning (RIC) is neuroprotective in experimental ischaemic stroke. Several neurohumoral, vascular and inflammatory mediators are implicated. We assessed the effect of RIC on plasma biomarkers using clinical data from the REmote ischaemic Conditioning After Stroke Trial (RECAST-1).
METHODS
RECAST-1 was a pilot sham-controlled blinded trial in 26 patients with ischaemic stroke, randomised to receive four 5-minute cycles of RIC within 24 hours of ictus. Plasma taken pre-intervention, immediately post-intervention and on day 4 was analysed for nitric oxide (nitrate/nitrite) using chemiluminescence and all other biomarkers by multiplex analysis. Biomarkers were correlated with clinical outcome (day 90 National Institutes of Health Stroke Scale [NIHSS], modified Rankin scale [mRS], Barthel index [BI]).
RESULTS
RIC reduced serum amyloid protein (SAP) and tissue necrosis factor-α (TNF-α) levels from pre- to post-intervention (n=13, 2-way ANOVA, p<0.05). Overall (n=26), increases in SAP pre- to post intervention and pre-intervention to day 4 were moderately-correlated with worse day 90 clinical outcomes. No consistent significant changes over time, or by treatment, or correlations with outcome were seen for other biomarkers.
CONCLUSIONS
RIC reduced SAP and TNF-α levels from pre- to post-intervention. Increases in plasma levels of SAP were associated with worse clinical outcomes after ischaemic stroke. Larger studies assessing biomarkers, safety and efficacy of RIC in acute ischaemic stroke are warranted to further understand these relationships
Discovery of Highly Selective Inhibitors of Calmodulin-Dependent Kinases That Restore Insulin Sensitivity in the Diet-Induced Obesity Mouse Model.
No full textPolymorphisms in the region of the calmodulin-dependent kinase isoform D (CaMK1D) gene are associated with increased incidence of diabetes, with the most common polymorphism resulting in increased recognition by transcription factors and increased protein expression. While reducing CaMK1D expression has a potentially beneficial effect on glucose processing in human hepatocytes, there are no known selective inhibitors of CaMK1 kinases that can be used to validate or translate these findings. Here we describe the development of a series of potent, selective, and drug-like CaMK1 inhibitors that are able to provide significant free target cover in mouse models and are therefore useful as tool compounds. Our results show that a lead compound from this series improves insulin sensitivity and glucose control in the diet-induced obesity mouse model after both acute and chronic administration, providing the first validation of CaMK1D as a target for diabetes therapeutics
The optimal surface for delivery of CPR: A systematic review and meta-analysis.
No full textAIM
To determine the effect of CPR delivery surface (e.g. firm mattress, floor, backboard) on patient outcomes and CPR delivery.
METHODS
We searched Medline, Cochrane Library and Web of Science for studies published since 2009 that evaluated the effect of CPR delivery surface in adults and children on patient outcomes and quality of CPR. We included randomised controlled trials only. We identified pre-2010 studies from the 2010 ILCOR evaluation of this topic. Two reviewers independently screened titles/ abstracts and full-text papers, extracted data and assessed risk of bias. Evidence certainty for each outcome was evaluated using GRADE methodology. Where appropriate, we pooled data in a meta-analysis, using a random-effects model.
RESULTS
Database searches identified 2701 citations. We included seven studies published since 2009. We analysed these studies together with the four studies included in the previous ILCOR review. All included studies were randomised controlled trials in manikins. Certainty of evidence was very low. Increasing mattress stiffness or moving the manikin from the bed to the floor did not improve compression depth. Use of a backboard marginally improved compression depth (mean difference 3 mm (95% CI 1-4).
CONCLUSION
The use of a backboard led to a small increase in chest compression depth in manikin trials. Different mattress types or delivery of CPR on the floor did not affect chest compression depth. PROSPERO CRD42019154791