Microsurgical limb reconstruction in the non-concordant patient.

Substance misuse is common in patients undergoing limb reconstruction secondary to open fractures and fracture related infection. This group risk breaching the social contract with their treating team through reduced engagement with perioperative care. Potential problems include limited social support, intravenous access, analgesia and withdrawal. These factors may negatively influence the range of treatments offered to this group. We aimed to establish the prevalence and outcomes of the problematically non-concordant cohort in our limb reconstruction population, who we aim to treat equitably even where non-concordance is suspected pre-operatively. A retrospective study was performed using our prospectively collected free flap limb reconstruction database from December 2021-October 2023. Patient electronic health records were reviewed for demographics, perioperative details and outcomes. Eighty patients were identified, with 8 identified as problematically non-concordant (10%). All patients had a background of substance abuse; smoking (100%), alcohol (75%), IVDU (63%). Pre-operative non-concordance included absconding (43%), staff abuse (57%) and refusal of care (57%). Post-operative non-concordance included smoking (75%), mobilisation against instructions (75%), absconding (63%). No patients had free flap failure. Inpatient stay varied from 8-83 days, average 28.50% of patients did not attend follow-up. The expanding horizon of microsurgery means complex reconstruction is offered to a greater range of patients. Surgical teams should ensure that this service is offered equitably, individualising treatment plans to achieve the best outcomes. Risk of non-concordance is usually evident pre-operatively. We advise early involvement of substance misuse teams, discharge support and an understanding team to achieve good outcomes.

Setting up a new microsurgical breast service in a non-tertiary hospital: Is it safe, and do outcomes compare to centres of excellence?

AIMS: Access to autologous reconstruction continues to be limited in some areas of the United Kingdom. This is, in part, due to the perceived difficulty offering this service outside of a large tertiary centre. We present our experience setting up a new microsurgical breast reconstruction service in a district hospital and compare our results to the published outcomes of large volume centres. METHODS: Patient data were collected prospectively from the start of the service to date (July 2018- July 2020) with the capture of demographics, management, and outcomes. The BREAST-Q tool was used preoperatively and at a minimum of 3 months. RESULTS: The first 40 patients undergoing DIEP reconstruction were included. Of these, 70% were immediate, mean age was 49 years (27-68) and BMI was 28.1 kg/m2 (22-32.5). In all, 50% had one or more co-morbidities other than breast cancer. Median length of stay was 3 days (2-6) with 75% of patients discharged on day 2 or 3. Ten patients' stay exceeded 3 days - mostly due to social reasons. Flap loss occurred in 1 patient (2.5%). Twenty-one patients developed complications (52%) within 90 days: seven Clavien-Dindo Grade I, two Grade II and ten Grade IIIb. Fat necrosis and mastectomy flap necrosis were the most common complications. Surgical intervention was higher in those needing adjuvant therapy. Patient-reported outcomes showed post-operative improvement across all domains except abdominal physical well-being at median 11.3 months. CONCLUSIONS: We present the shortest published length of stay for unilateral DIEP reconstructions. We are the first paper to publish patient-reported outcomes following a breast microsurgical enhanced recovery protocol. We demonstrate how a new microsurgical service, utilising an enhanced recovery protocol and careful patient selection can immediately achieve outcomes comparable to well-established centres. There is no reason why all patients should not have access to microsurgical breast reconstruction locally.

Analysis of the impact of EEA stapler size on risk of anastomotic complications in colorectal anastomosis: does size matter?

BACKGROUND: Colorectal anastomotic complications are dreaded and dramatically affect outcomes. Causes are multifactorial, with the size of the end-to-end anastomosis (EEA) stapler a modifiable factor and potential target for risk reduction. Our goal was to examine the impact of the EEA stapler size on the risk of anastomotic complications in left-sided colorectal resections. METHODS: A prospective divisional database was reviewed for consecutive elective left-sided resections with a colorectal anastomosis using an EEA stapler from January 2013 May 2018 inclusive. Patients were stratified into 25-29 mm or 30-33 mm cohorts. Patient and disease demographics, operative variables, and postoperative outcomes were evaluated. The main outcome measures were the rate and factors associated with anastomotic complications. RESULTS: Four hundred seventy-three cases were evaluated, 185 ( 39.1%) were in the 25-29 mm group and 288 (60.9%) in the 30-33 mm group. Patients were comparable in demographics and operative variables. More males were anastomosed with the 30-33 mm than with the 25-29 mm stapler (57.6% vs 28.6%, p < 0.01). Significantly more patients developed an anastomotic stricture with the 25-29 mm than with the 30-33 mm staplers (7.1% vs. 2.1%; p = 0.007). There was no significant difference in leak rates or reoperation/interventions between groups. On logistic regression, neither gender, operative indication nor approach were associated with anastomotic leak, readmission, or reoperation/intervention. Stapler size remained significantly associated with stricture (p = 0.032). CONCLUSIONS: The 25-29 mm EEA staplers were associated with an increased rate of anastomotic stricture compared to 30-33 mm staplers in left-sided colorectal anastomoses. As stapler size is a simple process measure that is easily modifyable, this is a potential target for improving anastomotic complication rates. Further controlled trials may help assess the impact of stapler size on improving patient and quality outcomes.

Poorly differentiated cutaneous squamous cell carcinomas have high incomplete excision rates with UK minimum recommended pre-determined surgical margins.

BACKGROUND: In the UK, the British Association of Dermatology-British Association of Plastic, Reconstructive and Aesthetic Surgery (BAD-BAPRAS) guidelines recommend excision of high-risk cutaneous squamous cell carcinomas (cSCCs), including poorly differentiated cSCCs, with a minimum peripheral margin of 6 mm1. OBJECTIVES: We assess whether the BAD-BAPRAS minimum margin achieves histological clearance in poorly differentiated cSCCs. PATIENTS AND METHODS: Demographics, surgical notes and histological reports from all patients having a primary cSCC excised at the Plastic Surgery Department of Addenbrooke's Hospital, Cambridge, UK, between January 2017 and April 2018 were analysed. Ordinal regression was performed for excision margin status versus histological grade by using size and site as co-variates. RESULTS: Of 296 cSCCs, 38(12.8%) were poorly differentiated. Patients with poorly differentiated cSCCs were older (81.1 years vs. 76.7 years, p = 0.038), had lesions on the face or scalp (89.2% vs. 52.1%, p = 0.0001), and had lymphovascular (10.5% vs. 0%, p = 0.001) or perineural invasion (15.8% vs. 2%, p = 0.002). Well-differentiated cSCCs were excised with an average peripheral margin of 4.72 mm (95% CI 4.25-5.18 mm), while poorly differentiated cSCCs were excised with a margin of 6.42 mm(95% CI 5.58-7.28 mm). Close or involved peripheral margins were seen in 3% of well-differentiated lesions but in 13.2% of poorly differentiated lesions (OR=45.02; p = 0.003). Deep margins were close in 13.1% (none involved) of well-differentiated lesions but close or involved in 50% of poorly differentiated lesions (OR=11.94; p = 0.001). CONCLUSIONS: We demonstrate that poorly differentiated cSCCs are frequently incompletely excised in both peripheral and deep planes, despite adherence to guidelines. The UK BAD-BAPRAS guidelines should be urgently updated in line with international consensus.

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.

The magnitude of Yo-Yo test improvements following an aerobic training intervention are associated with total genotype score.

Recent research has demonstrated that there is considerable inter-individual variation in the response to aerobic training, and that this variation is partially mediated by genetic factors. As such, we aimed to investigate if a genetic based algorithm successfully predicted the magnitude of improvements following eight-weeks of aerobic training in youth soccer players. A genetic test was utilised to examine five single nucleotide polymorphisms (VEGF rs2010963, ADRB2 rs1042713 and rs1042714, CRP rs1205 & PPARGC1A rs8192678), whose occurrence is believed to impact aerobic training adaptations. 42 male soccer players (17.0 ± 1y, 176 ± 6 cm, 69 ± 9 kg) were tested and stratified into three different Total Genotype Score groups; "low", "medium"and "high", based on the possession of favourable polymorphisms. Subjects underwent two Yo-Yo tests separated by eight-weeks of sports-specific aerobic training. Overall, there were no significant differences between the genotype groups in pre-training Yo-Yo performance, but evident between-group response differentials emerged in post-training Yo-Yo test performance. Subjects in the "high" group saw much larger improvements (58%) than those in the 'medium" (35%) and "low" (7%) groups. There were significant (p<0.05) differences between the groups in the magnitude of improvement, with athletes in the "high" and medium group having larger improvements than the "low" group (d = 2.59 "high" vs "low"; d = 1.32 "medium" vs "low"). In conclusion, the magnitude of improvements in aerobic fitness following a training intervention were associated with a genetic algorithm comprised of five single nucleotide polymorphisms. This information could lead to the development of more individualised aerobic training designs, targeting optimal fitness adaptations.

A genetic-based algorithm for personalized resistance training.

Association studies have identified dozens of genetic variants linked to training responses and sport-related traits. However, no intervention studies utilizing the idea of personalised training based on athlete's genetic profile have been conducted. Here we propose an algorithm that allows achieving greater results in response to high- or low-intensity resistance training programs by predicting athlete's potential for the development of power and endurance qualities with the panel of 15 performance-associated gene polymorphisms. To develop and validate such an algorithm we performed two studies in independent cohorts of male athletes (study 1: athletes from different sports (n = 28); study 2: soccer players (n = 39)). In both studies athletes completed an eight-week high- or low-intensity resistance training program, which either matched or mismatched their individual genotype. Two variables of explosive power and aerobic fitness, as measured by the countermovement jump (CMJ) and aerobic 3-min cycle test (Aero3) were assessed pre and post 8 weeks of resistance training. In study 1, the athletes from the matched groups (i.e. high-intensity trained with power genotype or low-intensity trained with endurance genotype) significantly increased results in CMJ (P = 0.0005) and Aero3 (P = 0.0004). Whereas, athletes from the mismatched group (i.e. high-intensity trained with endurance genotype or low-intensity trained with power genotype) demonstrated non-significant improvements in CMJ (P = 0.175) and less prominent results in Aero3 (P = 0.0134). In study 2, soccer players from the matched group also demonstrated significantly greater (P < 0.0001) performance changes in both tests compared to the mismatched group. Among non- or low responders of both studies, 82% of athletes (both for CMJ and Aero3) were from the mismatched group (P < 0.0001). Our results indicate that matching the individual's genotype with the appropriate training modality leads to more effective resistance training. The developed algorithm may be used to guide individualised resistance-training interventions.

Dual diagnosis of sarcoidosis and lymphoma.

BACKGROUND: Sarcoidosis is a multisystem granulomatous disease of unknown origin with pulmonary and extrapulmonary manifestations. Worldwide it is most often diagnosed in the third and fourth decades and most often affects Swedish, Danish and black patients. The association between malignancy and sarcoidosis has not been conclusively proven. Cancer can eventually occur in patients who have an established diagnosis of sarcoidosis for example, in sarcoidosis-lymphoma syndrome. Sarcoidosis can also subsequently develop in an oncology patient. There are multiple obstacles to confirming epidemiologically the linkage between sarcoidosis and malignancy. Histological verification and clinical acumen are needed to avoid misdiagnosis. The 18 fluorodeoxyglucose (18-FDG) PET has failed to provide a non invasive diagnostic method to differentiate neoplasia from benign sarcoid lesions and tissue diagnosis is essential before commencing a new therapeutic intervention in patients with lymphoma. METHODS: We report 3 cases of co-diagnosis of sarcoidosis and lymphoma that were seen in an oncology unit in Drogheda, Co. Louth. RESULTS: Our patients varied in the temporal association between the diagnosis of sarcoidosis and lymphoma as well as their demographic characteristics. CONCLUSION: These cases help to demonstrate the need for careful clinical, histological and radiological assessment.

Late-onset central hypoventilation syndrome: a family genetic study.

Congenital central hypoventilation syndrome is a rare disorder characterised by chronic alveolar hypoventilation, which becomes more pronounced during sleep and may be associated with neurocristopathies, such as Hirchsprung's disease. A mutation in the PHOX2B gene has recently been identified. In a family of both parents and five offspring, detailed clinical assessment, pulmonary function testing, overnight sleep studies and ventilatory responsiveness to progressive hypercapnia (V'(R,CO(2))) were performed, in addition to analysis of known genetic loci for this condition. The father and four of the offspring demonstrated features of central hypoventilation with nonapnoeic oxygen desaturation during sleep and diminished V'(R,CO(2)), despite normal pulmonary function. The lowest sleep saturation was median (range) 79% (67-83%) and V'(R,CO(2)) was 2.1 (0.03-4.3) L x min(-1) x kPa(-1). The normal values for the authors' centre (St Vincent's University Hospital, Dublin, Ireland) are 15-40 L x min(-1) x kPa(-1). An in-frame five amino acid polyalanine expansion of the PHOX2B gene was found in all affected subjects, while the mother and fifth child, who did not have features of central hypoventilation, had a normal PHOX2B gene. Magnetic resonance imaging of the brainstem in one severely affected child was normal. The present study of a unique family confirms that transmission of late-onset congenital central hypoventilation syndrome is autosomal dominant in nature.

Changes in outcome following surgery for colorectal cancer: one surgeon's experience.

BACKGROUND: Colorectal cancer (CRC) has the second highest mortality rate of all cancers in Ireland. Developments in imaging, surgical technique, and perioperative care in the last two decades have altered management. AIMS: To determine whether outcome following surgery for CRC in the mid-west has changed over a 22-year period. METHODS: Four hundred and twenty-two patients were divided into two time periods: Group A (1980-1991, n = 203) and Group B (1992-2002, n = 219) and demographic, inpatient, and survival data were reviewed. RESULTS: The mean age was 67 years, 59% were male. Group B patients had less advanced disease at presentation (Dukes' stage D 14% vs 22%, p < 0.05), fewer perioperative complications (13% vs 23%, p < 0.05), and fewer local recurrences (6.8% vs 11.8%, p < 0.05) than Group A. No difference in 30-day mortality rate or survival was detected. CONCLUSIONS: Although perioperative CRC management has improved, methods of earlier diagnosis and improvements in adjuvant therapy should be explored to improve survival.

Intranasal corticosteroid therapy for obstructive sleep apnoea in patients with co-existing rhinitis.

BACKGROUND: Increased nasal airflow resistance (NAR) may contribute to the pathophysiology of obstructive sleep apnoea syndrome (OSAS) but studies investigating the effects of relieving nasal obstruction in OSAS have produced differing results. There are no reports of intranasal corticosteroid therapy in adult OSAS patients with reversible nasal obstruction. METHODS: We evaluated an intranasal corticosteroid, fluticasone propionate, in 24 consecutive snorers with associated rhinitis using a randomised, placebo controlled, crossover design. Patients underwent polysomnography, snoring noise, and NAR measurements at baseline and after each 4 week treatment period. RESULTS: Twenty three patients completed the protocol and were divided into an apnoeic group (group A; 13 patients) and a non-apnoeic snoring group (group S; 10 patients) based on an apnoea-hypopnoea frequency (AHI) of > or =10/h or <10/h. AHI was significantly lower following treatment with fluticasone than with placebo in the total population (median (quartile range) 11.9 (22.6) v 20 (26.3); p<0.05) and in group A (23.3 (21.3) v 30.3 (31.9); p<0.05). Median (95% confidence interval) within subject differences for AHI were -3.2 (-17.7 to -0.2) in the total population and -6.5 (-29.5 to 1.8) in group A. NAR was also lower on fluticasone (2.74 (1.21) v 3.27 (1.38), p<0.01), within subject difference being -0.45 (95% CI -0.87 to -0.21). The changes in AHI and NAR in group A were significantly correlated (r=0.56; p<0.05). Snoring noise and sleep quality were unchanged but daily diary records indicated subjective improvements in nasal congestion and daytime alertness with fluticasone (p<0.02). CONCLUSIONS: Intranasal fluticasone is of benefit to some patients with OSAS and rhinitis. The data suggest that this form of nasal obstruction may contribute to the pathophysiology of OSAS.

Epidemiological trends in multiple births in the United States, 1971-1998.

The astounding rise in multiple births in the United States continues. We analyzed live birth files from the U.S. National Center for Health Statistics. Twin, triplet, quadruplet, and quintuplet+ rates were calculated for the period 1971-1977 and for each year between 1990 and 1998. Triplet rates were also computed within categories of mother's education and age. The twin rate increased from 1.8% in 1971-77 to 2.8% in 1998. The rate of triplets increased 5.9-fold, quadruplets 11.9-fold, and quintuplets+ 5.3-fold between 1971-77 and 1998. Increases in triplet rates were much more marked among births to university-educated women and women 30 years and older. Among women 45 years and older, the triplet rate was approximately fifty times higher in 1998 than in 1971-77. This group of older women (> or = 45 years) had the highest multiple birth rate in 1998.

Molecular events in transmembrane signaling via E-selectin. SHP2 association, adaptor protein complex formation and ERK1/2 activation.

E-selectin is a cytokine-inducible adhesion molecule that is expressed by activated endothelial cells at sites of inflammation. In addition to supporting rolling and stable arrest of leukocytes, there is increasing evidence that E-selectin functions in transmembrane signaling into endothelial cells during these adhesive interactions. We have previously shown that adhesion of HL-60 cells (which express ligands for E-selectin), or antibody-mediated cross-linking of E-selectin, results in formation of a Ras/Raf-1/phospho-MEK macrocomplex, extracellular signal-regulated protein kinase (ERK1/2) activation, and c-fos up-regulation. All of these downstream signaling events appear to require an intact cytoplasmic domain of E-selectin. Here we demonstrate that tyrosine 603 in the cytoplasmic domain of E-selectin is required for the E-selectin-dependent ERK1/2 activation. Tyrosine 603 plays an important role in mediating the association of E-selectin with SHP2, and the catalytic domain of SHP2 is, in turn, critical for E-selectin-dependent ERK1/2 activation. An adapter protein complex consisting of Shc.Grb2.Sos bridges between SHP2 and the Ras.Raf.phospho-MEK macrocomplex. These molecular events thus outline a mechanism by which cross-linking of E-selectin by engagement of ligands on adherent leukocytes can initiate a multifunctional signaling pathway in the activated endothelial cell at sites of inflammation.

Day case laparoscopic cholecystectomy is feasible.

BACKGROUND: Laparoscopic cholecystectomy is the operation of choice for cholelithiasis. AIMS: The aims of our study were to assess the feasibility of day case laparoscopic cholecystectomy (DCLC) in selected patients. METHODS: DCLC was introduced in this unit in July 1999. The first 50 patients were prospectively evaluated up to February 2001. RESULTS: All patients were under 55 years of age with an ASA grade of I (n = 48) or II (n = 2). The mean age was 41.1 years (range 20-55 years) and the male:female ratio was 1:6. All patients had a standard anaesthetic protocol. Patients were discharged 10 to 12 hours postoperatively with a pro forma, which was reviewed at one week in the clinic. The conversion rate was 2%. Three required overnight admission due to excessive nausea, hypertension and for an unforeseen psychosocial problem. Ninety per cent of patients were suitable for same day discharge. No patient required subsequent readmission. CONCLUSION: DCLC is feasible and safe in carefully selected patients and has the advantages of convenience and cost-effectiveness.

Maternal race/ethnicity and twinning rates in the United States, 1989-1991.

OBJECTIVE: To utilize United States birth certificate data (years 1989-1991) to examine the effects of race/ethnicity on twinning rates. STUDY DESIGN: We used a database of birth certificate data for the United States (years 1989-1991) available on CD-ROM from the United States National Center for Health Statistics. This linked birth/infant death data set included a total of 12,036,234 birth records, of which 279,073 were twins. Excluded from the analysis were 15,086 twin birth records (5.4%) based upon previously described exclusion criteria. Statistical analysis included a series of univariate analyses to determine the rates of twinning between different racial/ethnic groups correlated with maternal age, education, marital status and place of birth. Comparisons were analyzed using the chi 2 test, with significance at P < .05. RESULTS: The overall twinning rate was 2.26%, with the lowest rate observed in the group denoted non-Hispanic other (1.67%) and highest among non-Hispanic blacks (2.69%). Twinning rates within various groups representing Hispanics ranged from 1.76% to 2.08%. The twinning rate was significantly higher among U.S.-born as compared to non-U.S.-born women (2.34% vs. 1.88%, P < .005) except for Puerto Ricans, Cubans and Central/South Americans, for whom the reverse was true. Women aged 35-39 had the highest twinning rate (3.05%), whereas women aged 15-19 had the lowest; that trend persisted in all racial/ethnic groups. The study showed a nonsignificant relationship between marital status or education and twinning rate. CONCLUSION: Race/ethnicity studies can be useful in designing programs that may maximize health outcomes of twins in a racially diverse population.

Controlled oxygen therapy and carbon dioxide retention during exacerbations of chronic obstructive pulmonary disease.

Hypoxaemic patients with exacerbations of chronic obstructive pulmonary disease (COPD) are at some risk of carbon dioxide (CO2) retention during oxygen therapy. We quantified the risk of CO2 retention with oxygen therapy in COPD in 24 consecutive patients presenting to the accident and emergency department with acute exacerbations associated with hypercapnic respiratory failure (partial arterial pressure of oxygen [PaO2] < 8 kPa and partial pressure of CO2 [PaCO2] > or = 6.5 kPa). Only three patients developed clinically important CO2 retention (defined as a rise in PaCO2 > 1 kPa) with controlled oxygen therapy (24-40% by Venturi mask to maintain the oxygen saturation at 91-92%). These patients presented with more severe hypercapnia, but all three required only low-flow oxygen (24-28%). These findings suggest only a small risk of aggravating hypercapnia with controlled oxygen supplementation.