A multi-lesional analysis of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia: a single-centre analysis.

AIM: To conduct a multi-lesional computed tomography (CT) analysis of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) patients to determine volumetric changes in lesions over 5 years. MATERIALS AND METHODS: A retrospective case-note review was undertaken to identify 16 patients with histological and radiological features of DIPNECH between 2012-2021. Area and volume were calculated for 17 sets of lesions identified on high-resolution CT. Clinical data were extracted from electronic patient records, which included demographic data, outpatient clinic letters, histology reports, and imaging reports. RESULTS: One hundred and twenty-eight lesions were identified in 16 patients (one male, 15 female) and followed-up annually over a median 1,985 days (range 1,450-2,290). At year 1 follow-up, lesion area ranged from 1-48 mm2, and lesion volume ranged from 8-18,380 mm3; lesion area ranged from 1-45mm2 and lesion volume ranged from 11-17,800 mm3 and year 5. Half (8/16) of the patients had concomitant typical carcinoid tumours and one patient had an atypical carcinoid tumour. No statistically significant correlation (p<0.05) was found between lesion cross-sectional area or volume and duration of follow-up (years and days). No metastatic spread was observed at the time of analysis. CONCLUSIONS: No significant increase was observed in the size of over 100 lesions in patients with DIPNECH over a 5-year period and no metastasis occurred during the study period affirming the relatively indolent course of the disease.

Native pulmonary valve endocarditis requiring pulmonary valve replacement in adulthood: a case series.

Native pulmonary valve endocarditis is a rare phenomenon as native valve endocarditis tends to typically affect the left sided heart valves. However, the right-sided heart valves can be affected in patients with a history of intravenous drug use, whereby the tricuspid valve is most commonly affected. We present two cases who were diagnosed with native pulmonary valve endocarditis in the absence of congenital heart disease. In the first case, the native pulmonary valve endocarditis was probably a derivative of compounding factors of an enlarged underlying pulmonary artery and staphylococcal bacteraemia. In the second case, a common causal organism of native valve endocarditis following dental treatment and the resultant echocardiography findings was of significant interest. In summary, native pulmonary valve endocarditis is relatively rare complication in the adult population, especially in the absence of congenital heart disease.

A retrospective analysis of rates of allergic reaction to Patent V blue dye used in sentinel lymph node biopsies for melanoma.

Sentinel lymph node biopsies are a well-established component of the assessment and treatment pathway for patients with cutaneous melanoma in the UK. Commonly utilised techniques involve the use of blue dye which has an established risk of inducing allergic reactions in patients. Such reactions can be life-threatening, and this risk is important to highlight to patients. We conducted a retrospective review of all patients who had undergone this procedure at our melanoma centre in Cambridge, UK. From a group of 715 patients who received blue dye as part of the procedure, six patients suffered an allergic reaction (0.84%) with one of these treated as anaphylaxis. Our incidence of anaphylaxis is almost ten times greater than that reported in the NAP6 report led by the National Institute of Academic Anaesthesia and significantly higher than reported by others. We propose several reasons why our results differ from previous estimates. This study has focused only on patients undergoing a sentinel node procedure for melanoma, others have focused on such procedures performed on patients with breast cancer and some have combined the two. The administration technique, volume and anatomical distribution of disease all differ significantly from melanoma, possibly influencing rates and severity of allergic reactions.

Non-melanoma skin cancer activity during the COVID-19 pandemic- A single UK tertiary centre experience.

The pandemic caused by SARS-CoV-2 virus, also known as COVID-19, has generated shockwaves in medical and surgical practice. It has necessitated re-deployment of staff and resources to cater for the unpredictable increase in footfall and demand on healthcare systems. This study aimed to investigate how the restructuring of our service altered the triage and management of non-melanoma skin cancer (NMSC) during the pandemic's first wave rise and peak. We retrospectively analysed all patients who underwent a skin excision under local anaesthetic which revealed the presence of a basal cell carcinoma (BCC) or squamous cell carcinoma (SCC) on histopathological analysis between 1st February 2020 - 31st May 2020 compared with the same period in 2019. There was a 158% increase in patients with excision of lesions confirmed on histopathological analysis as a NMSC during the COVID-19 period (168 vs. 65). In 2020, more excisions were performed by consultants (42.9% v 21.5%, p = 0.002) with a lower proportion of excisions with a close margin (27.7% v 17.8%, p = 0.096) and an involved margin (3.1% v 1.8%, p = 0.62). Five of these patients had their further management altered due to service constraints at this time The resource constraints secondary to the pandemic have yielded beneficial service adaptations with the incorporation of a more efficient model for the NMSC service. The sustainability of this model and its impact on training will require further examination when non-urgent and benign elective workload is slowly reinstated and plastic surgery trainees return to their original posts.

Off-pump external pericardial patch repair for post-infarct left ventricular free wall rupture: a case series.

We describe an off-pump surgical approach to this challenging condition supported by our results from a case series, which would add to existing literature in the management of this life-threatening complication. We identified seven patients who underwent surgical intervention for left ventricular (LV) free wall rupture at our institution. They were all diagnosed to have cardiac tamponade secondary to free wall rupture of the LV in the presence of acute myocardial infarction. The surgical technique comprised of utilizing an external pericardial patch which was secured using surgical biological glues (fibrin-based sealants or gelatin hydrogels). The 30-day mortality, 1-year survival and 2-year survival were 57, 42 and 42%, respectively. Advanced age, female gender and use of cardiopulmonary bypass were characteristics that were not significantly associated with survival. We advocate the use of an off-pump external pericardial patch repair strategy as a 'bridge to recovery' in this extremely high-risk group of patients.

A retrospective study of 694 Basal Cell Carcinoma excisions to quantify deep margin documentation and clearance compared to histological type and surgical margin.

AIMS: Basal cell carcinoma (BCC) is the most common malignancy worldwide. Although rarely a risk to life, they are potentially destructive and disfiguring. Current treatment guidelines are predominantly based on low-risk BCC and make no recommendations regarding the deep excision margin. We aim to clarify the prevalence of high-risk BCC and appropriate surgical management of the deep margin. METHODS: Data of 556 patients presenting for primary excision of 694 basal cell carcinoma to CUH Plastic Surgery between January 2017 and April 2018 were collected by capture of demographics, surgical notes and histology. We defined the deep surgical margin as numbered anatomical planes, with subcutaneous fat as 0, the first plane under this as 1 and so forth. This allowed comparison of the surgical excision depth, and resulting deep margin histology, across disparate sites. Histological margin clearance was analysed using ordinal regression of age, site, size, histological type and surgical margin. This allowed identification of factors associated with clear, close or incomplete lesion excision. Subgroup analysis was then performed to make recommendations for surgical margins to achieve adequate lesion clearance. RESULTS: Six hundred ninety-four BCCs were identified, 66% were male and the average age of patients was 74 years. Of the BCCs, 49% were nodular but 39% were mixed. An infiltrative component was seen in 24% (mixed infiltrative), but only 4% were purely infiltrative. Mean size, site and patient age were similar across histological types. Deep margin involvement was very rare in nodular or superficial BCCs but occurred in 7% of pure infiltrative and 5% of mixed infiltrative. Peripheral margins were very rarely involved in nodular BCCs but occurred in 9% of mixed infiltrative and 10% infiltrative despite similar surgical margins. A deep margin of the first underlying anatomical plane resulted uninvolved margins in 95% of infiltrative or mixed infiltrative BCC, but subcutaneous fat was sufficient for clearance in 95% of nodular, superficial and mixed non-infiltrative BCC. CONCLUSIONS: High-risk BCC was a common finding in our patient population. This was based not only on site and size but also on histological type. Infiltrative and mixed infiltrative BCCs have a higher risk of close or involved deep margins than other types. We recommend that they are excised to the first underlying anatomical plane. Nodular, superficial and mixed non-infiltrative BCC can usually be safely excised with a cuff of fat alone.

Rectal and bladder dose reduction with the addition of intravaginal balloons to vaginal packing in intracavitary brachytherapy for cervical cancer.

PURPOSE: The use of intravaginal Foley balloons in addition to conventional packing during high-dose-rate (HDR) tandem and ovoids intracavitary brachytherapy (ICBT) is a means to improve displacement of organs at risk, thus reducing dose-dependent complications. The goal of this project was to determine the reduction in dose achieved to the bladder and rectum with intravaginal Foley balloons with CT-based planning and to share our packing technique. METHODS AND MATERIALS: One hundred and six HDR-ICBT procedures performed for 38 patients were analyzed for this report. An uninflated Foley balloon was inserted into the vagina above and below the tandem flange separately and secured in place with vaginal packing. CT images were then obtained with both inflated and deflated Foley balloons. Plan optimization occurred and dose volume histogram data were generated for the bladder and rectum. Maximum dose to 0.1, 1.0, and 2.0 cm(3) volumes for the rectum and bladder were analyzed and compared between inflated and deflated balloons using parametric statistical analysis. RESULTS: Inflation of intravaginal balloons allowed significant reduction of dose to the bladder and rectum. Amount of reduction was dependent on the anatomy of the patient and the placement of the balloons. Displacement of the organs at risk by the balloons allowed an average of 7.2% reduction in dose to the bladder (D0.1 cm(3)) and 9.3% to the rectum (D0.1 cm(3)) with a maximum reduction of 41% and 43%, respectively. CONCLUSIONS: For patients undergoing HDR-ICBT, a significant dose reduction to the bladder and rectum could be achieved with further displacement of these structures using intravaginal Foley balloons in addition to conventional vaginal packing.

Simultaneous spectrophotometric determination of celecoxib and diacerein in bulk and capsule by absorption correction method and chemometric methods.

Two methods, absorption correction and multivariate spectrophotometric methods were developed for simultaneous estimation of Celecoxib (CEL) and Diacerein (DIA) in combined dosage form. Absorption correction method involves direct estimation of DIA at wavelength 341 nm in which CEL has zero absorbance and shows no interference. For estimation of CEL, corrected absorbance was calculated at 253 nm due to the interference of DIA at this wavelength. Linearity was observed in the range of 6-22 µg mL(-1) for CEL and 3-11 µg mL(-1) for DIA. The method was validated as per ICH guidelines. Chemometric methods including classical least square (CLS), inverse least square (ILS), principal component regression (PCR) and partial least square (PLS) were studied for simultaneous determination of CEL and DIA in capsule using spectrophotometry. A set of 25 standard mixtures containing both drugs were prepared in range of 5-25 µg mL(-1) for CEL and 3-15 µg mL(-1) for DIA. Analytical figure of merit (FOM), such as sensitivity, selectivity, analytical sensitivity, limit of detection and limit of quantitation were determined for chemometric methods. The proposed methods were applied for determination of two components from combined dosage form.

Successful percutaneous coronary intervention in a patient with combined deficiency of FV and FVIII due to novel compound heterozygous mutations in LMAN1.

Percutaneous coronary intervention (PCI) in patients with congenital coagulation factor deficiencies presents a unique challenge. They are not only at increased risk of perioperative bleeding but can also suffer thrombosis of the stent as preventive anticoagulation and antiplatelet therapy is difficult. Several cases of successful PCI have been described in patients with haemophilia A and B, but there are no reports in patients with combined coagulation factor deficiencies. We used PCI to treat the coronary artery disease in a patient with the combined deficiency of factor V and factor VIII (F5F8D) and analysed the molecular basis of the disorder for this patient. A 68-year-old patient was admitted for urgent PCI with bare metal stent placement after the diagnosis of the F5F8D. Peripheral blood DNA was extracted for the sequence analysis of LMAN1 and MCFD2 genes. Mutations in LMAN1 was confirmed by molecular cloning of the PCR product and resequencing of the resulting clones. The patient underwent successful PCI with good long-term outcome. Our patient tolerated anticoagulation therapy well, with unfractionated heparin, and double antiplatelet therapy while he was initially supported with fresh frozen plasma and recombinant FVIII. Molecular analysis revealed that the patient carries unusual compound heterozygous frameshift mutations on the same microsatellite repeat region in exon 8 of LMAN1, one of which is a novel mutation (c.912delA). Our results suggest that patients with F5F8D can safely undergo PCI for coronary artery disease, with the treatment individualized to the specific patient.

Capillary versus venous haemoglobin determination in the assessment of healthy blood donors.

BACKGROUND AND OBJECTIVES: To determine the accuracy of fingerstick haemoglobin assessment in blood donors, the performance of a portable haemoglobinometer (HemoCue Hb 201+) was prospectively compared with that of an automated haematology analyzer (Cell-Dyn 4000). Haemoglobin values obtained by the latter were used as the 'true' result. MATERIAL AND METHODS: Capillary fingerstick samples were assayed by HemoCue in 150 donors. Fingerstick samples from two sites, one on each hand, were obtained from a subset of 50 subjects. Concurrent venous samples were tested using both HemoCue and Cell-Dyn devices. RESULTS: Capillary haemoglobin values (HemoCue) were significantly greater than venous haemoglobin values (HemoCue), which in turn were significantly greater than venous haemoglobin values by Cell-Dyn (mean ± SD: 14.05 ± 1.51, 13.89 ± 1.31, 13.62 ± 1.23, respectively; P < 0.01 for all comparisons among groups). Nine donors (6%) passed haemoglobin screening criteria (≥ 12.5 g/dl) by capillary HemoCue, but were deferred by Cell-Dyn values (false-pass). Five donors (3%) were deferred by capillary sampling, but passed by Cell-Dyn (false-fail). Substantial variability in repeated fingerstick HemoCue results was seen (mean haemoglobin 13.72 vs. 13.70 g/dl, absolute mean difference between paired samples 0.76 g/dl). Hand dominance was not a factor. CONCLUSIONS: Capillary samples assessed via a portable device yielded higher haemoglobin values than venous samples assessed on an automated analyzer. False-pass and false-fail rates were low and acceptable in the donor screening setting, with 'true' values not differing by a clinically significant degree from threshold values used to assess acceptability for blood donation.

The unwritten price of cosmetic tourism: an observational study and cost analysis.

INTRODUCTION AND AIMS: Cosmetic tourism, driven by the promise of inexpensive operations abroad, is increasingly popular despite warnings from professional bodies regarding associated risks. Increasing numbers of individuals have presented to our department requesting NHS treatment of complications from such surgery. We set out to characterize these patients and evaluate costs incurred through their assessment and management. MATERIAL AND METHODS: An observational study was conducted from 2007 to 2009 on patients presenting to a tertiary referral Plastic Surgery practice with complications of cosmetic tourism surgery. Demographic characteristics, as well as those related to the operation, were recorded. Hospital patient flow pathways were constructed, cost analysis performed using Patient Level Costing, and expenditure and profitability calculated. KEY RESULTS: Nineteen patients presented within the study period. Most operations were performed in Europe or Asia, and were primarily breast augmentation procedures (n=13). The principal complications were wound infection or dehiscence, and poor cosmetic results. Eleven patients received NHS treatment, at a cost of £120,841. The mean cost for all patients' management was £6360 (range: £114-£57,968), rising to £10,878 for those accepted for treatment. For 8 of the 9 patients (89%) for whom full patient level costing was available, the hospital incurred a financial loss. CONCLUSION: The costs to the NHS of managing complications of cosmetic tourism are substantial, and underestimated by central funding agencies.

Multiple myeloma presenting as solitary mass in the posterior fossa.

Intracranial plasma cell tumors are extremely rare and can either be solitary lesions or part of systemic multiple myeloma. We report a 42-year-old woman who presented with a posterior fossa mass and successfully underwent surgical resection, leading to the diagnosis of multiple myeloma. To our knowledge, this is the first reported case of multiple myeloma presenting as a posterior fossa mass lesion. This report highlights the importance of maintaining plasma cell tumor in the differential of intracranial mass with bony involvement. Furthermore, once the diagnosis is established, further work up is critical to evaluate for systemic disease.

A TRAM flap design refinement for use in delayed breast reconstruction.

Autologous breast reconstruction following mastectomy is commonly achieved using the free Transverse Rectus Abdominis Myocutaneous (TRAM) flap. Since its first description, refinements and modifications have resulted in improved operative techniques and more aesthetically pleasing reconstructions. Pre-operative flap design, however, is a relatively new concept that has not received much attention in the literature. Patients who undergo breast reconstruction may have large, ptotic contralateral breasts. In these patients there is a tendency to raise a large abdominal flap in an attempt to achieve symmetry, or simply a larger breast. This has the potential to lead to tight closure of the abdomen and the risk of subsequent wound problems. Reconstructions that are too small or have inadequate ptosis commit the patient to contralateral breast surgery to achieve symmetry. Pre-operatively designing the flap, using a template created from the opposite breast, can help achieve a good match, often reducing the need for contralateral breast surgery. Even when contralateral breast reduction surgery is planned in advance, many of these patients still require, and prefer, a large reconstruction in order to achieve a well-proportioned result. We present a design template that addresses these particular issues and in the senior author's hands has proved to be a very effective technique. Our technique allows raising an abdominal flap of less vertical height than traditionally used (thus reducing the risk of tight abdominal closure) and incorporates an inverted V-shaped flap of skin from the inferior mastectomy skin flap into the reconstruction. This allows more flap tissue to be available to fill the upper poles of the reconstructed breast and at the same time produces good ptosis.

Molecular physiology of oxygen-sensitive potassium channels.

Physiological adaptation to acute hypoxia involves oxygen-sensing by a variety of specialized cells including carotid body type I cells, pulmonary neuroepithelial body cells, pulmonary artery myocytes and foetal adrenomedullary chromaffin cells. Hypoxia induces depolarization by closing a specific set of potassium channels and triggers cellular responses. Molecular biology strategies have recently allowed the identification of the K+ channel subunits expressed in these specialized cells. Several voltage-gated K+ channel subunits comprising six transmembrane segments and a single pore domain (Kv1.2, Kv1.5, Kv2.1, Kv3.1, Kv3.3, Kv4.2 and Kv9.3) are reversibly blocked by hypoxia when expressed in heterologous expression systems. Additionally, the background K+ channel subunit TASK-1, which comprises four transmembrane segments and two pore domains, is also involved in both oxygen- and acid-sensing in peripheral chemoreceptors. Progress is currently being made to identify the oxygen sensors. Regulatory beta subunits may play an important role in the modulation of Kv channel subunits by oxygen.

Lipid and mechano-gated 2P domain K(+) channels.

The two pore domain K(+) channels TREK and TRAAK are opened by membrane stretch. The activating mechanical force comes from the bilayer membrane and is independent of the cytoskeleton. Emerging work shows that mechano-gated TREK and TRAAK are opened by various lipids, including long chain polyunsaturated anionic fatty acids and neutral cone-shaped lysophospholipids. TREK-1 shares the properties of the Aplysia neuronal S channel, a presynaptic background K(+) channel involved in behavioral sensitization, a simple form of learning.

Properties and modulation of mammalian 2P domain K+ channels.

Mammalian 2P domain K(+) channels are responsible for background or 'leak' K(+) currents. These channels are regulated by various physical and chemical stimuli, including membrane stretch, temperature, acidosis, lipids and inhalational anaesthetics. Furthermore, channel activity is tightly controlled by membrane receptor stimulation and second messenger phosphorylation pathways. Several members of this novel family of K(+) channels are highly expressed in the central and peripheral nervous systems in which they are proposed to play an important physiological role. The pharmacological modulation of this novel class of ion channels could be of interest for both general anaesthesia and ischaemic neuroprotection.