A practical approach to screening for carbapenemase-producing Enterobacterales- views of a group of multidisciplinary experts from English hospitals.

INTRODUCTION: Carbapenemase-producing Enterobacterales (CPE) are an important public health threat, with costly operational and economic consequences for NHS Integrated Care Systems and NHS Trusts. UK Health Security Agency guidelines recommend that Trusts use locally developed risk assessments to accurately identify high-risk individuals for screening, and implement the most appropriate method of testing, but this presents many challenges. METHODS: A convenience sample of cross-specialty experts from across England met to discuss the barriers and practical solutions to implementing UK Health Security Agency framework into operational and clinical workflows. The group derived responses to six key questions that are frequently asked about screening for CPE. KEY FINDINGS: Four patient groups were identified for CPE screening: high-risk unplanned admissions, high-risk elective admissions, patients in high-risk units, and known positive contacts. Rapid molecular testing is a preferred screening method for some of these settings, offering faster turnaround times and more accurate results than culture-based testing. It is important to stimulate action now, as several lessons can be learnt from screening during the COVID-19 pandemic, as well as from CPE outbreaks. CONCLUSION: Further decisive and instructive information is needed to establish CPE screening protocols based on local epidemiology and risk factors. Local management should continually evaluate local epidemiology, analysing data and undertaking frequent prevalence studies to understand risks, and prepare resources- such as upscaled screening- to prevent increasing prevalence, clusters or outbreaks. Rapid molecular-based methods will be a crucial part of these considerations, as they can reduce unnecessary isolation and opportunity costs.

Greater numbers of antral follicles in the ovary are associated with increased concentrations of glucose in uterine luminal fluid of beef heifers.

Increased antral follicles are associated with greater fertility and a uterine environment that is more supportive of early embryonic development in beef heifers. Glucose is a primary energy source for embryos, and glucose concentrations are elevated in uterine luminal fluid (ULF) of pregnant heifers. We hypothesized that ULF glucose concentrations and endometrial transcript abundance for glucose transporters on d16 after insemination would be greater in heifers with increased numbers of antral follicles. Heifers classified with either increased or diminished antral follicle counts were artificially inseminated following the CO-Synch protocol (d0). On d16 after insemination, reproductive tracts of heifers were collected at an abattoir to retrieve conceptuses to determine pregnancy. Uterine luminal fluid was collected, endometrium was biopsied, total RNA was extracted and glucose transporter transcript abundances were determined. Data were analyzed using the MIXED procedure of SAS with antral follicle group, pregnancy status, and the interaction as fixed effects. Glucose concentrations in ULF were greater in heifers with increased antral follicle numbers. Glucose ULF concentrations increased in pregnant heifers. Facilitated glucose transporter member 1 (SLC2A1) transcript abundance was increased in the endometrium of pregnant heifers but was not different due to antral follicle number or the interaction. Differences in uterine concentrations of glucose associated with antral follicle number could be due to another mechanism, since glucose transporters were not different between antral follicle numbers. Therefore, heifers with increased number of antral follicles have increased energy availability in the uterus to support trophoblast proliferation and function.

Treatment of Rotator Cuff Tears with platelet rich plasma: a prospective study with 2 year follow-up.

BACKGROUND: Surgical treatment of full-thickness rotator cuff (RC) tears is associated with generally good results. There is no consensus regarding treatment of partial thickness tears that fail conservative treatment. The purpose of this study was to look at the efficacy and confirm the safety of dual injection PRP into the shoulder of patients with rotator cuff pathology who have failed conservative treatment with followup to two years. METHODS: Seventy-one shoulders with MRI confirmed, rotator cuff pathology who failed conservative treatment, had dual PRP injection into the rotator cuff. Global improvement, Quick DASH and VAS scores were collected at 6, 12, and 24 months after treatment and comparison of means was used to analyze changes. RESULTS: No adverse events were seen in any patient. Based on global rating scores positive results were seen in 77.9 % of patients at 6 months, 71.6 % at 1 year, and 68.8 % of patients at 2 years. Mean VAS scores improved from 50.2 [CI 44.4-56.0] pre-injection to 26.2 [CI 19.5-32.9] at 6 months, 22.4[CI 16.1-28.7] at 1 year and 18.2 [CI 12.3-24.1] at 2 years (p < 0.0001 for all). The mean Q- DASH scores (0-100, 100 worse) improved from 39.2 [CI 34.3-44.1] for all patients before treatment to 20.7[CI 15.0-26.4] at 6 months, 18.0[CI 12.9-23.1] at 1 year, and 13.8 [CI 8.4-18.8] at 2 years (p < 0.0001 for all). No patient with partial tear had clinical evidence of progression to full thickness tear. When separated into subgroups based on rotator cuff status, all subgroups showed improvement. Patients in the > 50 % partial tear group had the best overall improvement based on Global Rating scores while those in the tendinitis group had the poorest outcomes. CONCLUSIONS: PRP injection is a safe and effective treatment for RC cuff injury in patients who have failed conservative treatment of activity modification and physical therapy without deterioration of results two years after treatment. Better results are obtained with greater structural tendon damage than in shoulders with inflammation without structural damage. TRIAL REGISTRATION: This is not a clinical trial.

Response to Letter to the editor: Acute Medicine Journal.

Editor- Thank you for giving us the opportunity to respond to the letter received regarding the Joint Royal College of Physicians Training Board (JRCPTB) curriculum for Acute Internal Medicine (AIM) that has previously been circulated for comment and consideration of implementation in August 2022. Dr Williamson is correct in asserting that the proposed curriculum hopes to produce doctors with generic professional and specialty specific capabilities needed to manage patients presenting with a wide range of medical symptoms and conditions. It does aim to produce a workforce that reflects the current trends of increasing patient attendances to both primary care and emergency departments- one that has a high level of diagnostic reasoning, the ability to manage uncertainty, deal with co-morbidities and recognise when specialty input is required in a variety of settings, including ambulatory and critical care.

Brangus cows have ovarian reserve parameters more like Brahman than Angus cows.

Bos indicus females have more surface antral follicles than Bos taurus females; however, histological studies demonstrated no difference in total number of primordial follicles between these two biological types of cattle. Primordial follicle density in the ovary was less in Nelore ovaries compared to Angus ovaries, but no studies have examined the primordial follicle density in Bos indicus cross-bred females. It, therefore, was hypothesized that primordial follicle density in the ovary would decrease as percentage Bos indicus increased. Ovaries were collected from cross-bred Angus (n = 32, no Bos indicus influence), Brangus (n = 15), or Brahman (n = 9) cows and prepared for histological evaluation. There was no difference in total number of primordial follicles per ovary between breeds (P > 0.10). When numbers of primordial follicles were expressed on a per gram of ovarian tissue basis, there were fewer primordial follicles per gram of ovarian tissue in Brangus and Brahman cows than in Angus cows (P < 0.05). Brangus cows did not differ from Brahman cows in primordial follicle density (P > 0.10). Differences in primordial follicle density could indicate differences in capacity of ovarian stroma to produce factors necessary for oogonial proliferation and primordial follicle formation among breeds. Identifying these factors could improve the aprroach for culturing pre-antral follicles of cattle. Furthermore, these results explain why ultrasonographic antral follicle counts may need to be adjusted to a greater threshold to predict size of the ovarian reserve and determine ovarian reserve related reproductive traits in Bos indicus females.

Intra-Articular Laser Treatment Plus Platelet Rich Plasma (PRP) Significantly Reduces Pain in Many Patients Who Had Failed Prior PRP Treatment.

Background: In our practice, Platelet Rich Plasma (PRP) injections effectively reduce pain in most, but not all, arthritic patients. When PRP treatment fails, joint replacement surgery is often the only good alternative. Surface Low-Level-Laser-Therapy (LLLT) has not been helpful for osteoarthrosis in our experience. We hypothesized that intra-articular laser (IAL) treatment combined with PRP would improve results in patients with prior ineffective PRP treatment. Methods: We offered Intra-articular Low-Level-Laser-Therapy (IAL) treatment simultaneously with repeat PRP injection to patients who had received no benefit from PRP alone. They were the treatment and also historical control group since all had failed PRP treatment alone. Thirty joints were treated: 22 knees, 4 hips, 2 shoulder glenohumeral joints and 2 first carpo-metacarpal (1st CMC). Results: No adverse events were seen at any time after treatment in any patient. Twenty-eight joints were available for re-evaluation: ≥ 40% improvement was seen in 46% (6 months), 32% (12 months) and 32% (24 months) post-treatment. Mean SANE scores improved significantly at 1 and 2 years. Thirteen patients failed treatment and had joint replacement. Conclusions: PRP with IAL allowed avoidance of surgery and good pain control at least two years post-treatment in nearly half of patients who had failed PRP treatment alone.

Trauma to the medial ray of the foot: A classification of patterns of injury and their management.

AIMS: Fractures and dislocations of the midfoot are relatively uncommon but can be life changing injuries. Within the literature, there has been scant specific reference to the identification and management of medial ray injuries in midfoot trauma. Moreover, it is appreciated that these injuries are associated with poor outcomes. We aim to clearly define these injury characteristics and demonstrate fixation techniques. PATIENTS AND METHODS: A retrospective review of the case notes and imaging was conducted for operatively treated midfoot injuries between January 2013 and January 2018. RESULTS: 161 patients were identified, 31 of these with imaging and operative diagnosis suggestive of medial ray injury. Studying these 31 injuries revealed five patterns of injury. CONCLUSION: When treating midfoot trauma, it is important to fully understand the injury pattern as this dictates the principles and techniques of fixation. Identification and knowledge of these five injury patterns will aid surgeons in future management of these injuries and may improve treatment outcomes.

Maternal age influences the number of primordial follicles in the ovaries of yearling Angus heifers.

The number of antral follicles detectable by ultrasonography in heifers is influenced by age of the dam, because daughters of primiparous cows have fewer antral follicles than daughters of mature cows. We, therefore, hypothesized that heifers with primiparous dams would have fewer primordial follicles in their ovaries than heifers born to mature (4+ y) cows. Angus heifers (n = 464) were submitted for ultrasonographic evaluation of antral follicle number at 325, 355, and 385 d of age. Ovaries were collected from a random subset of heifers (n = 79) and processed for histological evaluation to determine number of primordial follicles. A greater percentage of heifers with primiparous dams had a corpus luteum at first ultrasonographic examination; however, a greater percentage of heifers with multiparous dams had ovulated by the start of breeding (P < 0.01). Heifers with primiparous dams had fewer antral follicles detectable by ultrasonography (P < 0.01). Heifers with primparous dams had fewer surface antral follicles on their ovaries (P < 0.01), and the number of primordial follicles per histological section was less for heifers with primiparous dams (P = 0.02). These data indicate that the lesser number of antral follicles detectable by ultrasonography in heifers with primparous dams is due to less ovarian follicle reserves. Selecting replacement heifers from mature dams may result in daughters with greater fertility and reproductive longevity; however, further research is necessary to determine if interactions between size of the ovarian follicle reserve and age at puberty influence fertility and reproductive longevity in replacement heifers.

Treatment of Type Two Slap Lesion With Anatomic Suture Anchor Repair Without Biceps Tenotomy Or Tenodesis.

BACKGROUND: Poor results after repair of type 2 SLAP tears are relatively common and some have reported better results after biceps tenodesis or tenotomy than repair. In addition, some believe that the long head of the biceps is expendable. Therefore, many now favor biceps tenotomy or tenodesis over biceps anchor repair either in all patients or in older patients, reserving SLAP lesion repair only for young athletes. HYPOTHESIS: We hypothesized that repair of the biceps anchor of the labrum would be effective in all patients regardless of age provided that care was taken not to overtighten the labrum and that rotator cuff pain as the primary pain generator had been ruled out. METHODS: All patients with type 2 SLAP lesion repair by the senior author since he began repairing them with suture anchors were prospectively evaluated. Patients with more than one other concomitant procedure, simultaneous rotator cuff repair or worker's compensation status were excluded. RESULTS: 77% of patients were available for minimum two year followup. No patient had subsequent surgery or manipulation under anesthesis as a result of their SLAP repair. Standardized shoulder test score increased by 4 points. Mean SANE score decreased from 53 pre-op to 14 post-op. Results were the same in those over versus under 40 years of age. CONCLUSION: Anatomic repair of Type 2 SLAP lesions at the biceps anchor without biceps tenodesis or tenotomy can produce good results in patients of all ages.

A new and reliable classification system for fractures of the navicular and associated injuries to the midfoot.

AIMS: Fractures of the navicular can occur in isolation but, owing to the intimate anatomical and biomechanical relationships, are often associated with other injuries to the neighbouring bones and joints in the foot. As a result, they can lead to long-term morbidity and poor function. Our aim in this study was to identify patterns of injury in a new classification system of traumatic fractures of the navicular, with consideration being given to the commonly associated injuries to the midfoot. PATIENTS AND METHODS: We undertook a retrospective review of 285 consecutive patients presenting over an eight- year period with a fracture of the navicular. Five common patterns of injury were identified and classified according to the radiological features. Type 1 fractures are dorsal avulsion injuries related to the capsule of the talonavicular joint. Type 2 fractures are isolated avulsion injuries to the tuberosity of the navicular. Type 3 fractures are a variant of tarsometatarsal fracture/dislocations creating instability of the medial ray. Type 4 fractures involve the body of the navicular with no associated injury to the lateral column and type 5 fractures occur in conjunction with disruption of the midtarsal joint with crushing of the medial or lateral, or both, columns of the foot. RESULTS: In order to test the reliability and reproducibility of this new classification, a cohort of 30 patients with a fracture of the navicular were classified by six independent assessors at two separate times, six months apart. Interobserver reliability and intraobserver reproducibility both had substantial agreement, with kappa values of 0.80 and 0.72, respectively. CONCLUSION: We propose a logical, all-inclusive, and mutually exclusive classification system for fractures of the navicular that gives associated injuries involving the lateral column due consideration. We have shown that this system is reliable and reproducible and have described the rationale for the subsequent treatment of each type. Cite this article: Bone Joint J 2018;100-B:176-82.

Timing of transcriptomic and proteomic changes in the bovine placentome after parturition.

Proper post-partum reproductive performance is important for reproductive efficiency in beef cows, and dystocia decreases post-partum fertility. Crossbred beef cows (n = 1676) were evaluated for lifetime performance based on degree of dystocia at presentation of the first calf. Cows that experienced moderate or severe dystocia produced fewer calves during their productive life (P < 0.01). The exact mechanism is unclear, but may be due to the contributions of dystocia to abnormal placental separation. Proteolytic activity is hypothesized to contribute to placental separation in ruminants; however, when ovine placentomes were collected following caesarian section, no proteolytic activity was detected. We hypothesized that stage 2 of parturition was necessary to stimulate proteolysis and initiate placental separation. Serial placentome collections were performed on mature cows (n = 21 initiated; 7 with complete sampling) at hourly intervals for the first 2 h after expulsion of the calf. An intact piece of each placentome was fixed for histological evaluation, and a separate piece of caruncular and cotyledonary tissue from each placentome was frozen for transcriptomic and proteolytic analysis. A full set of placentomes was collected from only 7 of 21 cows at 0, 1, and 2 h, and all cows had expelled fetal membranes by 6 h. Histological, transcriptomic and proteolytic analysis was performed on placentomes from cows from which three placentomes were collected (n = 7). The microscopic distance between maternal and fetal tissues increased at 1 h (P = 0.01). Relative transcript abundance of matrix metalloprotease 14 (MMP14) tended to increase with time (P = 0.06). The relative transcript abundance of plasminogen activator urokinase-type (PLAU) was greater in caruncles than cotyledons (P = 0.01), and tended (P = 0.10) to increase in the caruncle between 0 and 2 h while remaining unchanged in the cotyledon over the same span of time. Greater PLAU and plasminogen activator tissue-type (PLAT) proteolytic activity was detected by zymography in the caruncle than the cotyledon immediately post-partum (P < 0.01). From these findings we conclude that 1) dystocia during the first parity decreases lifetime productivity in beef cattle, 2) the PA system is present at both the transcript and protein level in the bovine plactentome during parturition and 3) proteolytic activity is localized to the caruncular aspect of the placentome.

Beef heifers with diminished numbers of antral follicles have decreased uterine protein concentrations.

Previous research demonstrated a favorable relationship between the number of follicles detectable in the bovine ovary by ultrasonography and fertility, and bovine females with diminished numbers of antral follicles had smaller reproductive tracts. Therefore, we hypothesized that uterine function would be compromised in beef heifers with diminished numbers of antral follilcles. Angus heifers (n=480) were submitted for ultrasonographic evaluation of antral follicle number at 325 and 355d of age. After the second ultrasonographic examination, 40 pubertal heifers with the greatest average number of antral follicles (30.9±0.7) and 40 pubertal heifers with the lowest average number of antral follicles (14.2±0.7) were synchronized with two i.m. injections of prostaglandin F2α (25mg) administered 11d apart, and heifers were slaughtered on d6 (n=26 heifers/group) or d16 (n=14 heifers/group) of the resultant estrous cycle. The uterus was weighed, flushed for determination of protein content, and representative samples were fixed for determination of endometrial gland morphometry. Heifers in the Low group had fewer surface antral follicles and smaller reproductive tracts than heifers in the High group (P<0.01). Protein content of the uterine flushes was decreased in heifers in the Low group (P<0.01); however, there was no difference in the percent area of the endometrium occupied by endometrial glands. From these results, we conclude that the uterine environment of beef heifers with diminished numbers of antral follicles is less conducive to supporting early embryonic survival.

Symptomatic treatment or cast immobilisation for avulsion fractures of the base of the fifth metatarsal: a prospective, randomised, single-blinded non-inferiority controlled trial.

AIMS: The purpose of this study was to compare symptomatic treatment of a fracture of the base of the fifth metatarsal with immobilisation in a cast. Our null hypothesis was that immobilisation gave better patient reported outcome measures (PROMs). The alternative hypothesis was that symptomatic treatment was not inferior. PATIENTS AND METHODS: A total of 60 patients were randomised to receive four weeks of treatment, 36 in a double elasticated bandage (symptomatic treatment group) and 24 in a below-knee walking cast (immobilisation group). The primary outcome measure used was the validated Visual Analogue Scale Foot and Ankle (VAS-FA) Score. Data were analysed by a clinician, blinded to the form of treatment, at presentation and at four weeks, three months and six months after injury. Loss to follow-up was 43% at six months. Multiple imputations missing data analysis was performed. RESULTS: At four weeks and six months, symptomatic treatment proved non-inferior in terms of primary outcome. TAKE HOME MESSAGE: Immobilisation is no better than symptomatic treatment in the management of a fracture of the base of the fifth metatarsal when judged by PROMs. Significant loss to follow-up with this injury could be expected in longer term. Cite this article: Bone Joint J 2016;98-B:806-11.

Resonance-Enhanced Raman Scattering of Ring-Involved Vibrational Modes in the (1)B(2u) Absorption Band of Benzene, Including the Kekule Vibrational Modes ν(9) and ν(10).

Resonance Raman spectroscopy provides much stronger Raman signal levels than its off-resonant counterpart and adds selectivity by excitation tuning. Raman preresonance of benzene has been well studied. On-resonance studies, especially at phonon-allowed absorptions, have received less attention. In this case, we observe resonance of many of the vibration modes associated motion of the carbons in the ring while tuning over the (1)B2u absorption, including the related ν9 (CC stretch Herzberg notation, ν14 Wilson notation) and ν10 (CH-parallel bend Herzberg notation, ν15 Wilson notation) vibrational modes along with the ν2 (CC-stretch or ring-breathing Herzberg notation, ν1 Wilson notation) mode and multiples of the ν18 (CCC-parallel bend Herzberg notation, ν6 Wilson notation) vibrational mode. The ring-breathing mode is found to mix with the b2u modes creating higher frequency composites. Through the use of an optical parametric oscillator (OPO) to tune through the (1)B2u absorption band of liquid benzene, a stiffening (increase in energy) of the vibrational modes is observed as the excitation wavelength nears the (1)B2u absorption peak of the isolated molecule (vapor) phase. The strongest resonance amplitude observed is in the 2 × ν18 (e2g) mode, with nearly twice the intensity of the ring-breathing mode, ν2. Several overtones and combination modes, especially with ν2 (a1g), are also observed to resonate. Raman resonances on phonon-allowed excitations are narrow and permit the measurement of vibrations not Raman-active in the ground state.

High tibial osteotomy: indications, techniques, and postoperative management.

High tibial osteotomy is a safe and effective treatment for medial compartment arthrosis of the knee accompanied by varus alignment. This procedure has seen increasing use as an adjunct to cartilage restoration procedures, such as autologous chondrocyte and meniscal allograft transplantation, when angular deformity exists. The overall goals of high tibial osteotomy can be accomplished by several different techniques. The main indications for high tibial osteotomy are as a primary treatment for varus gonarthrosis and in conjunction with cartilage restoration procedures, such as autologous chondrocyte implantation or microfracture, where success rates are enhanced by correcting the varus deformity.

Long-term follow-up of flexor digitorum longus transfer and calcaneal osteotomy for stage II posterior tibial tendon dysfunction.

Flexor digitorum longus transfer and medial displacement calcaneal osteotomy is a well-recognised form of treatment for stage II posterior tibial tendon dysfunction. Although excellent short- and medium-term results have been reported, the long-term outcome is unknown. We reviewed the clinical outcome of 31 patients with a symptomatic flexible flat-foot deformity who underwent this procedure between 1994 and 1996. There were 21 women and ten men with a mean age of 54.3 years (42 to 70). The mean follow-up was 15.2 years (11.4 to 16.5). All scores improved significantly (p < 0.001). The mean American Orthopedic Foot and Ankle Society (AOFAS) score improved from 48.4 pre-operatively to 90.3 (54 to 100) at the final follow-up. The mean pain component improved from 12.3 to 35.2 (20 to 40). The mean function score improved from 35.2 to 45.6 (30 to 50). The mean visual analogue score for pain improved from 7.3 to 1.3 (0 to 6). The mean Short Form-36 physical component score was 40.6 (sd 8.9), and this showed a significant correlation with the mean AOFAS score (r = 0.68, p = 0.005). A total of 27 patients (87%) were pain free and functioning well at the final follow-up. We believe that flexor digitorum longus transfer and calcaneal osteotomy provides long-term pain relief and satisfactory function in the treatment of stage II posterior tibial tendon dysfunction.

Serial surveillance of carcinoid heart disease: factors associated with echocardiographic progression and mortality.

BACKGROUND: Carcinoid heart disease is a complication of metastatic neuroendocrine tumours (NETs). We sought to identify factors associated with echocardiographic progression of carcinoid heart disease and death in patients with metastatic NETs. METHODS: Patients with advanced non-pancreatic NETs and documented liver metastases and/or carcinoid syndrome underwent prospective serial clinical, biochemical, echocardiographic and radiological assessment. Patients were categorised as carcinoid heart disease progressors, non-progressors or deceased. Multinomial regression was used to assess the univariate association between variables and carcinoid heart disease progression. RESULTS: One hundred and thirty-seven patients were included. Thirteen patients (9%) were progressors, 95 (69%) non-progressors and 29 (21%) patients deceased. Baseline median levels of serum N-terminal pro-brain natriuretic peptide (NT-proBNP) and plasma 5-hydroxyindoleacetic acid (5-HIAA) were significantly higher in the progressors. Every 100 nmol l(-1) increase in 5-HIAA yielded a 5% greater odds of disease progression (OR 1.05, 95% CI: 1.01, 1.09; P=0.012) and a 7% greater odds of death (OR 1.07, 95% CI: 1.03, 1.10; P=0.001). A 100 ng l(-1) increase in NT-proBNP did not increase the risk of progression, but did increase the risk of death by 11%. CONCLUSIONS: The biochemical burden of disease, in particular baseline plasma 5-HIAA concentration, is independently associated with carcinoid heart disease progression and death. Clinical and radiological factors are less useful prognostic indicators of carcinoid heart disease progression and/or death.

Greater trochanteric hip pain.

In the patient with lateral hip pain, there is a broad differential diagnosis, making appropriate evaluation and management challenging. Greater trochanteric pain syndrome is a term used to denote chronic lateral hip pain and encompasses several painful soft tissue diagnoses including coxa saltans, trochanteric bursitis, and gluteus minimus and medius tendon tears. An overview of these common causes is presented through a series of cases that encompass the anatomic associations, classic presentations, diagnostic tests, and management strategies unique to each disorder. By reviewing this information, we hope to provide clinicians with the tools to evaluate greater trochanteric pain syndrome efficiently and effectively.