Prolonged interval to surgery following neoadjuvant chemoradiotherapy in locally advanced rectal cancer: A meta-analysis of randomized controlled trials.

BACKGROUND: Long-course neoadjuvant chemoradiotherapy (NCRT), followed by surgery after an interval of 6-8 weeks, represents standard of care for patients with locally advanced rectal cancer (LARC). Increasing this interval may improve rates of complete pathological response (pCR) and tumour downstaging. We performed a meta-analysis comparing standard (SI, within 8 weeks) versus longer (LI, after 8 weeks) interval from NCRT to surgery. METHODS: PubMed, Embase, and Cochrane databases were searched up to 31 August 2022. Randomized controlled trials (RCTs) comparing SI with LI after NCRT for LARC were included. The primary endpoint was pCR rate. Secondary endpoints included rates of R0 resection, circumferential resection margin positivity (+CRM), TME completeness, lymph node yield (LNY), operative duration, tumour downstaging (TD), sphincter preservation, mortality, postoperative complications, surgical site infection (SSI) and anastomotic leak (AL). Random effects models were used to calculate pooled effect size estimates. RESULTS: Four RCTs encompassing 867 patients were included. There were 539 males (62.1%). LI was associated with a higher pCR rate (OR 0.61, 95%CI â€‹= â€‹0.39-0.95, p â€‹= â€‹0.03), and more TD (OR 0.60, 95%CI â€‹= â€‹0.37-0.97, p â€‹= â€‹0.04) compared to SI. However, there was no difference in rates of R0 resection (p â€‹= â€‹0.87), +CRM (p â€‹= â€‹0.66), sphincter preservation (p â€‹= â€‹0.26), incomplete TME (p â€‹= â€‹0.49), LNY (p â€‹= â€‹0.55), SSI (p â€‹= â€‹0.33), AL (p â€‹= â€‹0.20), operative duration (p â€‹= â€‹0.07), mortality (p â€‹= â€‹0.89) or any surgical complication (p â€‹= â€‹0.91). CONCLUSIONS: A LI to surgery after NCRT for LARC increases pCR and TD rates. Local recurrence or survival were not assessed due to unavailable data. We recommend deferring TME until after an interval of 8 weeks following completion of NCRT.

Arthroplasty of the trapeziometacarpal joint with or without bioabsorbable polylactide scaffold (RegJoint™) interposition.

The RegJoint™, a bioabsorbable polylactide scaffold, was introduced in 2011 for scaphometacarpal interposition following trapeziectomy for osteoarthritis. As previous clinical trials provided controversial results, we aimed to prove the non-inferiority of RegJoint™ interposition. In this retrospective study, first metacarpal suspension arthroplasty alone (SA) was compared to suspension with RegJoint™ interposition (RJ). Thirty-four patients with 37 treated thumbs (SA: 14; RJ: 23) were assessed clinically and radiologically at a mean follow-up of 5.3 ± 2.6 years (SA: 7.96; RJ: 3.73). Patient-reported outcomes were measured on three questionnaires (DASH, PRWE and PEM) and a visual analogue pain scale; there were no significant differences between the 2 groups. Clinical assessment comprised range of motion, opposition, pain, first-ray length, hand span, prominence, instability, force and sensitivity to touch. The RJ group showed significantly better palmar abduction (p = 0.026); the other outcome parameters were comparable in the 2 groups. Follow-up radiographs showed osteolysis in 2 SA hands and 3 RJ hands (p = 0.551). First-ray length had decreased by a mean 4.7 ± 2.7 mm at follow-up (SA: -3.8; RJ: -5.2; p = 0.056). No signs of adverse tissue reactions were observed. We conclude that RegJoint™ spacers do not produce more complications than suspension alone but provide no added benefit.

Proceedings of resources for optimal care of acute care and emergency surgery consensus summit Donegal Ireland.

BACKGROUND: Opportunities to improve emergency surgery outcomes exist through guided better practice and reduced variability. Few attempts have been made to define optimal care in emergency surgery, and few clinically derived key performance indicators (KPIs) have been published. A summit was therefore convened to look at resources for optimal care of emergency surgery. The aim of the Donegal Summit was to set a platform in place to develop guidelines and KPIs in emergency surgery. METHODS: The project had multidisciplinary global involvement in producing consensus statements regarding emergency surgery care in key areas, and to assess feasibility of producing KPIs that could be used to monitor process and outcome of care in the future. RESULTS: Forty-four key opinion leaders in emergency surgery, across 7 disciplines from 17 countries, composed evidence-based position papers on 14 key areas of emergency surgery and 112 KPIs in 20 acute conditions or emergency systems. CONCLUSIONS: The summit was successful in achieving position papers and KPIs in emergency surgery. While position papers were limited by non-graded evidence and non-validated KPIs, the process set a foundation for the future advancement of emergency surgery.

Retrospective analysis of 30-day mortality for emergency general surgery admissions evaluating the weekend effect.

BACKGROUND: The weekend effect describes excess mortality associated with hospital admission on Saturday or Sunday. This study assessed whether a weekend effect exists for patients admitted for emergency general surgery. METHODS: Data for emergency general surgical admissions to National Health Service hospitals in the Northern Deanery in England between 2000 and 2014 were collected, including demographics, co-morbidities, diagnoses, operations undertaken and outcomes. The primary outcome of interest was in-hospital death within 30 days of admission. Cox regression analysis was undertaken with adjustment for co-variables. RESULTS: There were 12 100 in-hospital deaths within 30 days of admission (3·3 per cent). The overall 30-day mortality rate reduced significantly during the 15-year interval studied, from 5·4 per cent (2000-2004) to 4·0 per cent (2005-2009) and 2·9 per cent during 2010-2014 (P < 0·001). There was no significant mortality difference for patients admitted at the weekend in adjusted Cox models (hazard ratio (HR) 1·00 for Saturday and 0·90 for Sunday, versus Wednesday). There was a significantly higher mortality for operations undertaken at the weekend (HR 1·15 for Saturday and 1·40 for Sunday; P = 0·021 and P < 0·001 respectively). The significantly increased mortality that was evident for emergency surgery at the weekend compared with weekdays in 2000-2004 (HR 1·46 for Saturday and 1·55 for Sunday; both P < 0·001); had reduced by 2010-2014, when the adjusted mortality risk was not significant (HR 1·18 for Saturday and 1·12 for Sunday). CONCLUSION: During the past 15 years there has been a weekend effect in patients undergoing emergency general surgery based on day of operation, but not day of admission. Overall mortality for emergency general surgery has improved significantly, and in the past 5 years the increased mortality risk of weekend surgery has reduced.

Preoperative curves of greater magnitude (>70°) in adolescent idiopathic scoliosis are associated with increased surgical complexity, higher cost of surgical treatment and a delayed return to function.

BACKGROUND: Surgical procedures to correct larger curve magnitudes >70° in patients with adolescent idiopathic scoliosis (AIS) are still common; despite their increased complexity, limited research has assessed the effect of preoperative curve severity on outcomes. AIM: This study aimed to examine the impact of preoperative curves >70° vs. those ≤70° on perioperative, functional and financial outcomes in patients with AIS undergoing posterior spinal fusion (PSF). METHODS: Seventy seven eligible AIS patients who underwent PSF were prospectively followed-up, until return to preoperative function was reported. Preoperative curves >70° vs. ≤70° were analysed in relation to surgical duration, estimated blood loss, perioperative complications, length of hospitalisation, return to function and cost of surgical treatment per patient. RESULTS: Severe preoperative curves >70°, identified in 21 patients (27.3 %), were associated with significantly longer surgical duration (median 6.5 vs. 5 h, p = 0.001) and increased blood loss (median 1250 vs. 1000 ml, p = 0.005)-these patients were 2.1 times more likely to receive a perioperative blood product transfusion (Relative Risk 2.1, CI 1.4-2.7, p = 0.004). Curves >70° were also associated with a significantly delayed return to school/college, and an increased cost of surgical treatment (€33,730 vs. €28,620, p < 0.0001). CONCLUSION: Surgeons can expect a longer surgical duration, greater intraoperative blood loss and double the blood product transfusion risk when performing PSF procedures on AIS patients with curves greater than 70° vs. those ≤70°. Surgical correction for curves >70°, often as a result of lengthy surgical waiting lists, also incurs added expense and results in a partial delay in early functional recovery.

Characterization of comorbid factors in hip fracture related in-hospital mortality.

It is important to delineate factors which influence in-hospital mortality rates following a hip fracture. The current study aimed to identify the nature and frequency of comorbidities prevalent in this patient cohort. A retrospective chart review of cases of in-patient mortality following admission for a hip fracture was performed. These cases (n=127) were characterized for comorbidities, complications, medical status indicators, and other contributory factors. Cardiovascular 104 (81.9%), respiratory 66 (52.0%), genitourinary 41 (32.3%), psychiatric 41 (32.3%), vascular 40 (31.5%), and gastrointestinal 40 (31.5%), are the physiological systems, most commonly associated with comorbidity amongst hip fracture patients who succumb to in-hospital mortality. Renal failure, pneumonia, sepsis, myocardial infarction, congestive cardiac failure (CCF), respiratory failure, and Clostridium difficile infection are conditions which are associated with postoperative complications leading to in-patient mortality. Analysis of medical status indicators illustrated an inverse correlation between ASA scores and postoperative survival time, in this cohort-of hip fracture patients (R2 = 0.9485).

Epstein-Barr virus positive inflammatory pseudo-tumour of the spleen: A case report and literature review.

INTRODUCTION: Epstein-Barr virus positive inflammatory pseudo-tumour (IPT) of the spleen is an uncommon, frequently asymptomatic entity, which is typically picked up as an incidental finding on imaging. PRESENTATION OF CASE: We present a case of EBV positive IPT of the spleen which presented as an incidental finding on CT in a patient with a history of malignancy. Splenectomy was performed. DISCUSSION: IPTs are benign spindle cell lesions of varying aetiology, which can arise in a variety of tissues, including the spleen. In situ hybridisation showed strong staining for Epstein-Barr virus RNA in our case, in common with many similar lesions described in the literature. The differential diagnosis of such spindle cell tumours is discussed. CONCLUSION: Radiologically, EBV positive spindle cell tumours are indistinguishable from malignant lesions such as lymphoma and diagnosis is made on histology, usually at splenectomy.

The incidence of ulnocarpal complaints after distal radial fracture in relation to the fracture of the ulnar styloid.

Two hundred distal radial fractures, with a mean follow up of 20 months (range 6-49), were divided into three groups according to the presence and healing status of an ulnar styloid fracture. The patients underwent both clinical and radiological examination and completed two different questionnaires. One hundred and one, of 200 distal radial fractures, were associated with an ulnar styloid fracture. Forty-six of these developed an ulnar styloid nonunion. The authors encountered significantly higher pain scores (ulnar sided pain p = 0.012), a higher rate of DRUJ instability (p = 0.032), a greater loss of motion and grip strength (p = 0.001), and a poorer clinical outcome in cases with an ulnar styloid fracture, but no differences were apparent when those with healed ulnar styloid fractures or ulnar styloid nonunions were compared (p > 0.05). The investigators propose that the incidence of ulnocarpal complaints following distal radial fracture depends on the presence but not the healing status of an ulnar styloid fracture.

Determinants of insulin responsiveness in young women: Impact of polycystic ovarian syndrome, nitric oxide, and vitamin D.

BACKGROUND: Polycystic ovary syndrome (PCOS) is associated with incremental risk of atherosclerosis and possibly of cardiovascular events. Insulin resistance (IR) occurs frequently in PCOS subjects, which might be one of the mechanisms involved in engendering such risk. We sought to evaluate whether the impact of other factors potentially associated both with PCOS and with IR might differentially modulate degree of IR in women with and without PCOS. METHODS AND RESULTS: We measured body mass index (BMI), hs-CRP, plasma concentrations of asymmetric dimethylarginine (ADMA), vitamin D (25(OH)D3) levels and platelet responsiveness to nitric oxide donor sodium nitroprusside (NO responsiveness) in 47 young women (n=27 with PCOS and n=20 weight-matched controls) without metabolic syndrome, hypertension or overt cardiovascular disease. We performed univariate and multivariate regression analyses to establish correlates of the quantitative insulin-sensitivity check index (QUICKI), as a marker of IR. On univariate analysis, plasma 25(OH)D3 levels and low NO responsiveness tended to be direct correlates with QUICKI in the entire subject group. BMI, hs-CRP, and ADMA levels were significant inverse correlates of QUICKI in PCOS subjects, but not in subjects without PCOS. On multivariate analysis, NO responsiveness, and 25(OH)D3 levels, but not PCOS per se were significant correlates of QUICKI. CONCLUSIONS: In the entire cohort of young women, low NO responsiveness and vitamin D deficiency are associated with low QUICKI, while elevated ADMA, inflammatory activation and obesity are selectively associated with low QUICKI in PCOS subjects; this may contribute to the increased cardiovascular risk associated with this syndrome.

Screening for subclinical Cushing's syndrome in type 2 diabetes mellitus: low false-positive rates with nocturnal salivary cortisol.

The diagnosis of subclinical Cushing's syndrome (SCS) is important, but its relative rarity amongst patients with common metabolic disorders requires a simple test with a low false-positive rate. Using nocturnal salivary cortisol (NSC), which we first validated in patients with suspected and proven Cushing's syndrome, we screened 106 overweight patients with type 2 diabetes mellitus, a group at high risk of SCS and nontumoral hypothalamic-pituitary-adrenal axis perturbations. Our hypothesis was that a lower false-positive rate with NSC was likely, compared with that reported with the dexamethasone suppression test (DST) (10-20%), currently the foundation of diagnosis of SCS. No participant had clinically apparent Cushing's syndrome. Three participants had an elevated NSC but further testing excluded SCS. In this study, NSC had a lower false-positive rate (3%) than previously reported for the DST. Given the reported excellent performance of NSC in detection of hypercortisolism, the low false-positive rate in SCS suggests NSC may be superior to the DST for SCS screening. The NSC and DST should be compared directly in metabolic disorder patients; although our data suggest the patient group will need to be substantially larger to definitively determine the optimal screening test.

First clinical experience with a novel forearm boom.

The optimal forearm boom should facilitate dynamic investigation of the wrist and approaches for wrist arthroscopy. It should be safely fixed at the operating table without any contact with the patient. It must be compatible with the arm of any patient and should be sterilisable. Repositioning of distal radius fractures, fluoroscopy and insertion of Kirschner-wires should not be restricted. According to these criteria the current investigators designed a new forearm boom which was subsequently used in 19 wrist arthroscopies and 9 distal radius fracture fixations. Twenty-eight patients with heights between 150 and 205 cm and forearm lengths between 17.5 to 37 cm were treated. Preoperatively, wrist motion was tested in those 19 wrists, that underwent wrist arthroscopy, before and after fixation by the forearm boom and any restriction due to usage of the novel device was found. The new forearm boom satisfied all of the criteria cited above. Therefore the current authors believe the new forearm boom may be valuable for the indications mentioned.

3D visualized robot assisted reduction of femoral shaft fractures: evaluation in exposed cadaveric bones.

The main problems in intra-medullary nailing of femoral shaft-fractures are leg-length discrepancies and rotational differences with an incidence of 2-18% and 20-40% respectively. These may lead to severe postoperative sequelae such as additional correctional operations and difficult rehabilitation. Insufficient visualization can be considered the main reason for these complications. Finally, retention of the fragments in the correct alignment before nail insertion is difficult. To overcome these problems we established a robotic telemanipulator system to support the reduction process. It was evaluated in 30 fractures of embalmed human femora. Specially programmed software used an image-dataset which was acquired by an isocentric 3D fluoroscope. For visualization, a surface projection was generated. Localization and tracking of the fragments and the robot-arm as well as accuracy measurement was performed by using an optical navigation system. Manipulation was controlled via a force-feedback joystick. This way, collisions of the fragments were transmitted back to the surgeon. At the end of the reduction the robot could rigidly retain the fragments' position.

Achilles tendon repair: Achillon system vs. Krackow suture: an anatomic in vitro biomechanical study.

BACKGROUND: Limited open repairs of acutely ruptured Achilles tendon, using the Achillon device, are becoming a frequently used method of treatment. To date there are no biomechanical studies comparing the strength of the Achillon repair to the Krackow repair. This study provides a direct comparison of the strength of these two repair techniques. METHODS: Using 10 paired cadaveric Achilles tendon specimens; repairs were performed using a Krackow technique on one specimen and a repair with the Achillon Suture System on the contralateral specimen. All repairs were made with identical suture material. Specimens were tested for ultimate strength using a servo-hydraulic testing device. FINDINGS: The mean load to failure of the control group (Krackow suture) was 276N (standard deviation 87.0), and for the experimental group (Achillon suture) was 342N (standard deviation 92.8). Using a Wilcoxon test this result was found to be statically significant (P=0.03). INTERPRETATION: The current study has demonstrated that the Achillon repair is stronger in a cadaveric biomechanical study than the Krackow repair using identical sutures. This provides biomechanical evidence to support the continued use of the limited open repair as opposed to the traditional open repair.

Open wedge tibial osteotomies influence on axial rotation and tibial slope.

Inaccurate coronal plane and inadvertent sagittal plane realignment is a common problem after high tibial osteotomies (HTO). While the effects of an HTO on the coronal have been studied extensively, the influence on axial rotation has not been described in detail. The current study examines the effect of HTO on tibial rotation in the axial plane as determined by computed tomography. We hypothesized that high tibial osteotomies have an effect on tibial rotation in the axial plane and that depending on the predefined osteosynthetic implant used, a corresponding change in the tibial slope would occur. HTOs with a tapered 12.5 mm Puddu plate were performed on 13 limbs under computer-navigated control. All limbs were CT scanned before and after the HTO. Using specific software, the CT data was converted into 3D computer models and the following parameters compared: (a) varus-valgus leg alignment; (b) tibial axial rotation; (c) tibial slope (including determination of lateral and medial tibial slope, (d) leg length including determination of the tibial length. Results revealed: (a) a varus-valgus alignment increase of 11 +/- 4.7 degrees (P < 0.005); (b) an axial tibial rotation of 2.7 +/- 6.3 degrees (P < 0.075) occurred with external rotation in 10 out of 13 limbs (12 degrees max external; 9.5 degrees max internal); (c) tibial slope revealed differences of 4.2 +/- 5.9 degrees (P < 0.025); (d) the tibial length increased after HTO by 7.1 +/- 3.7 mm (P < 0.005), while there was no significant change in overall leg length. In summary, tibial rotation does occur in high tibial osteotomies with though the degree of external rotation in this study tended not to be statiscally significant. Tapered implants do not guarantee maintenance of a steady tibial slope, while tibial length changes significantly when HTOs are performed. The combined use of CT and 3D software measurement techniques is reproducible and can be used without any further invasive fixation devices.

Resistance-modifying agents. Part 7: 2,6-disubstituted-4,8-dibenzylaminopyrimido[5,4-d]pyrimidines that inhibit nucleoside transport in the presence of alpha1-acid glycoprotein (AGP).

The synthesis and biological evaluation of potent 4,8-dibenzylaminopyrimidopyrimidine nucleoside transport inhibitors, with reduced binding to alpha1-acid glycoprotein, is reported.

Potentiation of the cytotoxicity of thymidylate synthase (TS) inhibitors by dipyridamole analogues with reduced alpha1-acid glycoprotein binding.

Dipyridamole has been shown to enhance the in vitro activity of antimetabolite anticancer drugs through the inhibition of nucleoside transport. However, the clinical potential of dipyridamole has not been realized because of the avid binding of the drug to the plasma protein alpha1-acid glycoprotein (AGP). Dipyridamole analogues that retain potent nucleoside transport inhibitory activity in the presence of AGP are described and their ability to enhance the growth inhibitory and cytotoxic effects of thymidylate synthase (TS) inhibitors has been evaluated. Three dipyridamole analogues (NU3026, NU3059 and NU3060) were shown to enhance the growth inhibitory activity of the TS inhibitor CB3717 and block thymidine rescue in L1210 cells. The extent of potentiation at a fixed analogue concentration (10 microM) was related to the potency of inhibition of thymidine uptake. A further analogue, NU3076, was identified, which was more potent than dipyridamole with a Ki value for inhibition of thymidine uptake of 0.1 microM compared to 0.28 microM for dipyridamole. In marked contrast to dipyridamole, inhibition of thymidine uptake by NU3076 was not significantly affected by the presence of AGP (5 mg ml(-1)). NU3076 and dipyridamole produced equivalent potentiation of the cytotoxicity of the non-classical antifolate TS inhibitor, nolatrexed, in L1210 cells with both compounds significantly reducing the LC90, by > threefold in the absence of salvageable thymidine. Thymidine rescue of L1210 cells from nolatrexed cytotoxicity was partially blocked by both 1 microM NU3076 and 1 microM dipyridamole. NU3076 also caused a significant potentiation of FU cytotoxicity in L1210 cells. These studies demonstrate that nucleoside transport inhibition can be maintained in the absence of AGP binding with the dipyridamole pharmacophore and that such analogues can enhance the cytotoxicity of TS inhibitors.

Oestrogen deficiency impairs intestinal calcium absorption in the rat.

1. The effects of ovariectomy on the relationships between calcium consumption and calcium balance and its components were assessed in adult (10-14 months) sham-operated and ovariectomized (Ovx) rats fed a semi-synthetic diet with the calcium content varying between 0.02 and 0.4%. 2. Adaptation to dietary calcium restriction was monitored for 47 days from commencement of a 0.02 % Ca diet. 3. Response to 1,25-dihydroxyvitamin D (20 ng kg-1 day-1) administration in sham and Ovx rats and oestradiol (E2) (20 microgram kg-1 day-1) replacement in Ovx rats was assessed in rats fed a 0.05% Ca diet. 4. Ovx rats had lower intercepts for the relationships between calcium consumption and both calcium balance (P < 0.005) and intestinal calcium absorption (P < 0.005) compared with sham rats, but 1,25-dihydroxyvitamin D was not reduced in Ovx rats. 5. The magnitude of adaptation to dietary calcium restriction was unaffected by ovariectomy. 6. Intestinal calcium absorption was stimulated by an equivalent amount in sham and Ovx rats following 1, 25-dihydroxyvitamin D administration, although this did not reach statistical significance for sham (sham, t = 1.91, n.s.; Ovx, t = 3. 18, P < 0.05). 7. Oestradiol replacement in Ovx rats induced a marked increase in intestinal calcium absorption (t = 8.25, P < 0. 005), without stimulating circulating 1,25-dihydroxyvitamin D levels and led to a marked increase in calcium balance (t = 6.89, P < 0. 005). 8. These data indicate that the impairment of intestinal calcium absorption following ovariectomy is not the result of reduced circulating 1,25-dihydroxyvitamin D or reduced intestinal responsiveness to 1,25-dihydroxyvitamin D. Moreover E2 stimulates intestinal calcium absorption probably by a direct effect on the intestine.

An oil-based model of inhalation anesthetic uptake and elimination.

An oil-based model was developed as a physical simulation of inhalation anesthetic uptake and elimination. It provides an alternative to animal models in testing the performance of anesthesia equipment. A 7.5-1 water-filled manometer simulates pulmonary mechanics. Nitrogen and carbon dioxide flowing into the manometer simulate oxygen consumption and carbon dioxide production. Oil-filled chambers (180 ml and 900 ml) simulate the uptake and washout of halothane by the vessel-rich and muscle tissue groups. A 17.2-1 air-filled chamber simulates uptake by the lung group. Gas circulates through the chambers (3.7, 13.8, and 25 l/min) to simulate the transport of anesthetic to the tissues by the circulatory system. Results show that during induction and washout, the rate of rise in endtidal halothane fraction simulated by the model parallels that measured in patients. The model's end-tidal fraction changes correctly with changes in cardiac output and alveolar ventilation. The model has been used to test anesthetic controllers and to evaluate gas sensors, and should be useful in teaching principles underlying volatile anesthetic uptake.