Real-world effectiveness of airway clearance techniques in children with cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) is commonly characterised by thick respiratory mucus. From diagnosis, people with CF are prescribed daily physiotherapy, including airway clearance techniques (ACTs). ACTs consume a large proportion of treatment time, yet the efficacy and effectiveness of ACTs are poorly understood. This study aimed to evaluate associations between the quality and quantity of ACTs and lung function in children and young people with CF. METHODS: Project Fizzyo, a longitudinal observational cohort study in the UK, used remote monitoring with electronic pressure sensors attached to four different commercial ACT devices to record real-time, breath-by-breath pressure data during usual ACTs undertaken at home over 16 months in 145 children. ACTs were categorised either as conformant or not with current ACT recommendations based on breath pressure and length measurements, or as missed treatments if not recorded. Daily, weekly and monthly associations between ACT category and lung function were investigated using linear mixed effects regression models adjusting for clinical confounders. RESULTS: After exclusions, 45 224 ACT treatments (135 individuals) and 21 069 days without treatments (141 individuals) were analysed. The mean±sd age of participants was 10.2±2.9 years. Conformant ACTs (21%) had significantly higher forced expiratory volume in 1 s (FEV1) (mean effect size 0.23 (95% CI 0.19-0.27) FEV1 % pred per treatment) than non-conformant (79%) or missed treatments. There was no benefit from non-conformant or missed treatments and no significant difference in FEV1 between them (mean effect size 0.02 (95% CI -0.01-0.05) FEV1 % pred per treatment). CONCLUSIONS: ACTs are beneficial when performed as recommended, but most people use techniques that do not improve lung function. Work is needed to monitor and improve ACT quality and to increase the proportion of people doing effective airway clearance at home.

Quantity and quality of airway clearance in children and young people with cystic fibrosis.

Children and young people with CF (CYPwCF) get advice about using positive expiratory pressure (PEP) or oscillating PEP (OPEP) devices to clear sticky mucus from their lungs. However, little is known about the quantity (number of treatments, breaths, or sets) or quality (breath pressures and lengths) of these daily airway clearance techniques (ACTs) undertaken at home. This study used electronic pressure sensors to record real time breath-by-breath data from 145 CYPwCF (6-16y) during routine ACTs over 2 months. ACT quantity and quality were benchmarked against individual prescriptions and accepted recommendations for device use. In total 742,084 breaths from 9,081 treatments were recorded. Individual CYPwCF maintained consistent patterns of ACT quantity and quality over time. Overall, 60% of CYPwCF did at least half their prescribed treatments, while 27% did fewer than a quarter. About 77% of pre-teens did the right number of daily treatments compared with only 56% of teenagers. CYPwCF usually did the right number of breaths. ACT quality (recommended breath length and pressure) varied between participants and depended on device. Breath pressures, lengths and pressure-length relationships were significantly different between ACT devices. PEP devices encouraged longer breaths with lower pressures, while OPEP devices encouraged shorter breaths with higher pressures. More breaths per treatment were within advised ranges for both pressure and length using PEP (30-31%) than OPEP devices (1-3%). Objective measures of quantity and quality may help to optimise ACT device selection and support CYPwCF to do regular effective ACTs.

Case report: paradoxically reversible perfusion defects on vasodilator stress imaging in a case of metastatic coronary compression.

Background: Patients with malignancy who experience metastasis to cardiac structures may exhibit ST-segment elevations and acute coronary syndrome (ACS) through poorly understood pathophysiologic mechanisms. We present a case in which vasodilator stress cardiovascular magnetic resonance provides unique insight into one such patient who suffered from recurrent episodes resembling ACS. Case summary: A 58-year-old male with metastatic lung adenocarcinoma presented with refractory angina and dynamic inferior electrocardiogram changes. The patient was referred for adenosine stress cardiovascular magnetic resonance, revealing multiple territories of abnormal perfusion during rest with improvement during adenosine infusion. Subsequent computed tomography displayed tumour encasement of the right coronary artery. Taken together, vasodilator-responsive extrinsic compression of multiple epicardial coronary arteries was suspected. Outpatient oncology follow-up for chemoimmunotherapy initiation was arranged with the hope that reducing tumour burden might alleviate coronary compression. However, in the ensuing months, the patient's disease advanced beyond the point of which his symptoms could be controlled medically, and he was ultimately enrolled in hospice care. Discussion: Encasement of coronary arteries can result in anginal symptoms if their position impairs coronary arterial flow. The presented case highlights the unique manner in which these lesions might behave on stress cardiac magnetic resonance imaging. Clinicians who encounter such unusual findings on vasodilator stress imaging should consider metastatic lesions to the cardiac structures on the differential diagnosis.

Presence and activation of pro-inflammatory macrophages are associated with CRYAB expression in vitro and after peripheral nerve injury.

BACKGROUND: Inflammation constitutes both positive and negative aspects to recovery following peripheral nerve injury. Following damage to the peripheral nervous system (PNS), immune cells such as macrophages play a beneficial role in creating a supportive environment for regrowing axons by phagocytosing myelin and axonal debris. However, a prolonged inflammatory response after peripheral nerve injury has been implicated in the pathogenesis of negative symptoms like neuropathic pain. Therefore, the post-injury inflammation must be carefully controlled to prevent secondary damage while allowing for regeneration. CRYAB (also known as alphaB-crystallin/HSPB5) is a small heat shock protein that has many protective functions including an immunomodulatory role in mouse models of multiple sclerosis, spinal cord injury, and stroke. Because its expression wanes and rebounds in the early and late periods respectively after PNS damage, and CRYAB null mice with sciatic nerve crush injury display symptoms of pain, we investigated whether CRYAB is involved in the immune response following PNS injury. METHODS: Sciatic nerve crush injuries were performed in age-matched Cryab knockout (Cryab-/-) and wildtype (WT) female mice. Nerve segments distal to the injury site were processed by immunohistochemistry for macrophages and myelin while protein lysates of the nerves were analyzed for cytokines and chemokines using Luminex and enzyme-linked immunosorbent assay (ELISA). Peritoneal macrophages from the two genotypes were also cultured and polarized into pro-inflammatory or anti-inflammatory phenotypes where their supernatants were analyzed for cytokines and chemokines by ELISA and protein lysates for macrophage antigen presenting markers using western blotting. RESULTS: We report that (1) more pro-inflammatory CD16/32+ macrophages are present in the nerves of Cryab-/- mice at days 14 and 21 after sciatic nerve crush-injury compared to WT counterparts, and (2) CRYAB has an immunosuppressive effect on cytokine secretion [interleukin (IL)-ß, IL-6, IL-12p40, tumor necrosis factor (TNF)-α] from pro-inflammatory macrophages in vitro. CONCLUSIONS: CRYAB may play a role in curbing the potentially detrimental pro-inflammatory macrophage response during the late stages of peripheral nerve regeneration.

Protocol for Project Fizzyo, an analytic longitudinal observational cohort study of physiotherapy for children and young people with cystic fibrosis, with interrupted time-series design.

INTRODUCTION: Daily physiotherapy is believed to mitigate the progression of cystic fibrosis (CF) lung disease. However, physiotherapy airway clearance techniques (ACTs) are burdensome and the evidence guiding practice remains weak. This paper describes the protocol for Project Fizzyo, which uses innovative technology and analysis methods to remotely capture longitudinal daily data from physiotherapy treatments to measure adherence and prospectively evaluate associations with clinical outcomes. METHODS AND ANALYSIS: A cohort of 145 children and young people with CF aged 6-16 years were recruited. Each participant will record their usual physiotherapy sessions daily for 16 months, using remote monitoring sensors: (1) a bespoke ACT sensor, inserted into their usual ACT device and (2) a Fitbit Alta HR activity tracker. Real-time breath pressure during ACTs, and heart rate and daily step counts (Fitbit) are synced using specific software applications. An interrupted time-series design will facilitate evaluation of ACT interventions (feedback and ACT-driven gaming). Baseline, mid and endpoint assessments of spirometry, exercise capacity and quality of life and longitudinal clinical record data will also be collected.This large dataset will be analysed in R using big data analytics approaches. Distinct ACT and physical activity adherence profiles will be identified, using cluster analysis to define groups of individuals based on measured characteristics and any relationships to clinical profiles assessed. Changes in adherence to physiotherapy over time or in relation to ACT interventions will be quantified and evaluated in relation to clinical outcomes. ETHICS AND DISSEMINATION: Ethical approval for this study (IRAS: 228625) was granted by the London-Brighton and Sussex NREC (18/LO/1038). Findings will be disseminated via peer-reviewed publications, at conferences and via CF clinical networks. The statistical code will be published in the Fizzyo GitHub repository and the dataset stored in the Great Ormond Street Hospital Digital Research Environment. TRIAL REGISTRATION NUMBER: ISRCTN51624752; Pre-results.

Experience With 15 Years of Laparoscopic Donor Nephrectomy: Review of 2500 Cases.

BACKGROUND: Laparoscopic donor nephrectomy (LDN) is considered the gold standard for live donor nephrectomies owing to lesser pain, shorter hospitalization, and earlier return to normal activities, yet it remains a technically challenging surgery. Repetition of a highly skilled task such as LDN should lead to improved performance reflected in shorter surgery times and a decrease in adverse events. METHODS: The records of over 2524 LDNs from February 2004 to June 2019 were evaluated for duration of surgery (from incision time to clamping of the renal artery) and occurrence of complications. RESULTS: The mean duration of surgery ± SD from incision to clamp time for the first 100 cases at the inception of LDN was 166.13 ± 33.28 minutes whereas it was 124.59 ± 35.91 minutes for the best 100 consecutive cases in 2015 with a decrease of 41 minutes duration of surgery from incision to artery clamping. The adverse events were accessory renal artery injury (n = 10), splenic laceration (n = 2), bowel and mesocolon injuries (n = 12), venous or arterial clip slippage (n = 4), inferior vena cava tear (n = 2) pneumothorax (during stapler application, n = 1), missing gauze counts (n = 1), chylous ascites (n = 1), ureteric thermal injury (n = 2), and renal parenchyma injury (n = 3). CONCLUSIONS: LDN is a technically demanding surgery where surgeon experience appears to affect operative metrics such as operative time. The occurrence of intraoperative complications appears to be acceptably low, although serious complications are a possibility.

Immunocytochemical detection of minichromosome maintenance protein 2 as a potential urinary-based marker of bladder cancer: A prospective observational study.

INTRODUCTION: Numerous biomarkers have been investigated for the diagnosis and follow-up of patients with bladder cancer, but none has achieved desirable acceptability. In the search of biomarkers, minichromosome maintenance protein 2 (MCM2), a cell cycle regulatory protein, was investigated and the preliminary results were promising. Hence, we conducted a study to investigate the role of immunocytochemical (ICC) detection of MCM2 in voided urinary samples of patients with bladder cancer in an Indian population. MATERIALS AND METHODS: A prospective comparative observational study was performed. One hundred and fifty patients with a mass lesion in the bladder and 100 controls were enrolled in this prospective study from June 2017 to-December 2018. Fifty-milliliter of voided urine sample was collected and processed for ICC staining of MCM2. RESULTS: Fifty, 100, and 200 positive MCM2 cells as a cutoff value has shown a sensitivity of 87.33% (80.93%-92.20%), 84.67% (77.89%-90.02%), and 80.67% (73.43%-86.65%), respectively. The specificity of 50, 100, and 200 positive MCM2 cells was 97% (91.48%-99.38%), 99% (94.55%-99.97%), and 100% (96.38%-100.0%), respectively. CONCLUSION: ICC detection of MCM2 in voided urinary samples has good sensitivity and specificity for the detection of bladder cancer. Hence, it can be used as a potential marker for the detection of bladder cancer.

Is liquid-based cytology an alternative to conventional cytology for detection of malignant cells in urine of bladder cancer? Eastern Indian prospective observational study.

OBJECTIVE: Conventional cytology (CC) is a widely employed biomarker for the detection of bladder cancer, but due to its decreased sensitivity, liquid-based cytology (LBC) has been studied. Despite its improved cell-free background, decreased cell degeneration, and an automated slide preparation technique, it shows a variable rate of malignant cells detection. Thus, we did this study to compare the positivity of LBC with CC in eastern Indian population. MATERIAL AND METHODS: A total of 150 patients who underwent a transurethral resection of bladder tumor (June 2017 to December 2018) were enrolled. Pre-operative CC and LBC were processed from freshly voided urine samples. The malignant cells detection rate and influential factors were noted and compared. RESULTS: The detection of malignant cells by LBC was higher compared to CC (37.3% vs. 25.3%; p<0.0001). Among 59 high-grade tumors, 59% and 86% slides were positive for CC and LBC, respectively (p<0.0001). Even in the background of hematuria, LBC showed a better detection (43.33% by LBC vs. 23.66% by CC; p<0.0001). CONCLUSION: The present study concludes that LBC offers a better detection of malignant cells in the urine of patients with bladder tumor as compared to CC. The detection of malignant cells by LBC is even better in the background of hematuria.

Long-term Safety of Minimally Invasive Left Ventricular Assist Device Discontinuation for Myocardial Recovery.

BACKGROUND: Left ventricular assist devices (LVADs) play important roles in advanced heart failure (HF) management. In patients who experience myocardial recovery, the LVAD is often explanted via a resternotomy, which may negatively impact the newly recovered heart. We describe a case-series of LVAD discontinuation using a minimally invasive approach, focusing on thromboembolic phenomenon and infection rates in long-term follow-up. METHODS: Our study is a single-center, retrospective case series of patients with myocardial recovery after mechanical unloading with an LVAD. Patients underwent outflow graft ligation through a minimally invasive approach with driveline excision. Postdiscontinuation, patients obtained serial transthoracic echocardiograms for a minimum of 6 months and followed with our heart failure specialist. RESULTS: All 7 recovery patients had nonischemic cardiomyopathy and included 4 women (57%). Mean age was 44.3 ± 15.6 years. Median LVAD support duration was 454 (interquartile range, 326 to 1096) days. Intensive care unit length of stay and total length of stay were 3.4 ± 1.9 days and 6.3 ± 2.3 days, respectively. Blood transfusion rate was 0.86 ± 1.1 units. At a median follow-up of 874 (interquartile range, 864 to 1007) days, no patients developed thromboembolic phenomena despite use of aspirin only for prophylaxis. One patient experienced driveline infection, who had persistent driveline infection before procedure. CONCLUSIONS: This minimally invasive approach for LVAD discontinuation through outflow graft ligation, driveline removal, and LVAD stoppage in setting of myocardial recovery avoids resternotomy risks. Despite leaving the LVAD in situ, there was no risk of thromboembolism or infection associated with residual hardware.

Pain and anxiety assessment during cystourethroscopy in males using voiding instruction: A prospective, randomized controlled study.

INTRODUCTION: Office cystourethroscopy is one of the common and most frequent urological procedures. Pain and anxiety during the procedure might lead to noncompliance and incomplete cystoscopic examination. Negotiating cystoscope through external sphincter is the most painful and uncomfortable distressing part of cystoscopy. To overcome this, manual compression of irrigation bag during cystoscopy has been used and found to be helpful. Numerous other methods were also studied. Despite these, cystoscopy is still painful and causes anxiety in patients. External sphincter gets relaxed naturally during the act of micturition. Based on this principle, pain and anxiety were studied with voiding instruction during cystourethroscopy. OBJECTIVE: To study the effect of voiding instruction on anxiety and pain during cystourethroscopy using the Hamilton Anxiety Rating Scale (HAM-A) and visual analogue scale (VAS), in a well-matched Eastern Indian male patient population in a prospective, randomized pattern. METHODS: A total of 100 male patients were recruited from those who underwent cystourethroscopy examination in SSKM Hospital and were prospectively randomized into two groups: cystoscopy with or without voiding instruction. Pre- and postprocedure HAM-A score and postprocedure VAS score were recorded. RESULTS: The mean postprocedural pain (VAS) score between voiding instructed and noninstructed groups reached statistical significance: 3.06 ± 1.98 (Range, 2-5) and 5.16 ± 2.86 (Range, 4-8), respectively (P < 0.001). Preprocedure HAM-A score was similar between both groups. Postprocedure median HAM-A score was statistically significantly lower (mean 17.86 ± 2.8 vs. 19.76 ± 3.12; P < 0.001) in voiding instructed group. CONCLUSION: Pain and anxiety level during cystourethroscopy examination in males can be significantly reduced when the patient is instructed to void during cystourethroscopy examination.

Retroperitoneal Single Port Versus Transperitoneal Multiport Donor Nephrectomy: A Prospective Randomized Control Trial.

BACKGROUND: Laparoscopic donor nephrectomy (LDN) converted a retroperitoneal (RP) procedure into a transperitoneal (TP) operation with reports of bowel and solid organ injuries leading to mortality in occasional cases. Laparoscopic RP donor nephrectomy can reduce these risks but never became popular because of the muscle cutting approach. Lumbotomy incision can be used to approach retroperitoneum by incising fascial planes, eliminating disadvantages of the RP approach. This report compares the outcomes of the standard multiport TP LDN with translumbar laparoendoscopic single-site donor nephrectomy (LESS-DN). METHODS: Between January 2016 and June 2017, 50 voluntary kidney donors out of 267 donors were randomized to undergo LESS-DN vs LDN. Donors with body mass index ≥30 kg/m2, multiple renal arteries, and right-sided nephrectomy were excluded from the study. Postoperative pain, duration of surgery, length of graft vessels and ureter, warm ischemia time, intraoperative blood loss, incision length, convalescence period, duration of hospital stay, and recipients' creatinine at discharge were compared among both the groups. Pain assessment was done using visual analogue scale (VAS). RESULTS: The RP group experienced lesser pain (VAS score 0.3 ± 0.3 vs 1.1 ± 0.0, p = 0.000), lesser analgesic requirement (186 ± 51.07 mg vs 254 ± 62.7 mg, p = 0.000), and faster convalescence (7.0 ± 3.0 days vs 10.7 ± 3.3 days, p = 0.00) related to smaller cumulative incision (7.8 ± 0.8 cm vs12.4 ± 2.0 cm, p = 0.00), and had reduced operative time (142 ± 26.2 minutes vs 170.8 ± 34.75 minutes, p = 0.001) and blood loss. Other recorded parameters were similar in both the groups. CONCLUSIONS: The single port RP approach significantly reduced postoperative pain and hastened recovery when compared with the TP approach. Converting to a RP approach presents an opportunity for surgeons to further reduce morbidity associated with the donor nephrectomy.

Complicated triple gallbladder: clinical presentation and surgical approach.

We report a patient with previous biliary symptoms and endoscopic interventions who presented with clinical features suggestive of choledocholithiasis. Open surgical exploration disclosed three gallbladders with copious stones and varying degrees of acute and chronic inflammation. Literature review revealed only 16 previously reported cases. We review the aetiology of triple gallbladder as being due to failure of rudimentary bile ducts to regress during embryological development, as well as the classification scheme of triple gallbladder based on size, location and number. We also discuss the clinical evaluation and appropriate surgical management of this entity, as triple gallbladders can be associated with cholecystitis or carcinoma.