Good functional outcome following severe neutropenic enterocolitis and perforation in a 48-year-old woman undergoing chemotherapy for breast cancer.

Neutropenic enterocolitis (NEC) is a life-threatening bowel condition, usually resulting from chemotherapy, with a mortality rate thought to be as high as 50%. Markers of poor prognosis include gastrointestinal perforation and bowel wall thickness radiologically detected to be greater than 10 mm. NEC is associated with severe neutropenia and predominantly affects the large bowel; however, we present a case of severe NEC with oesophageal perforation requiring transfer to a specialist upper gastrointestinal unit for corrective stenting. Despite initial bowel wall thickness of 20 mm in the ascending colon, two discrete episodes of bowel perforation and an inpatient stay totalling 89 days, the patient was discharged with full independence, a good quality of life and a plan for curative mastectomy plus axillary clearance.

Austrian syndrome, ceftriaxone-induced agranulocytosis and COVID-19.

We present a case of a 75-year-old woman with Austrian syndrome: pneumonia, meningitis and endocarditis all due to Streptococcus pneumoniae Transoesophageal echocardiogram demonstrated a large mitral valve vegetation with severe mitral regurgitation. She was treated with intravenous ceftriaxone and listed for surgical repair of her mitral valve. Preoperatively, she developed an idiosyncratic drug-induced agranulocytosis secondary to ceftriaxone, which resolved on cessation of the medication. However, while awaiting neutrophil recovery, she developed an acute deterioration, becoming critically unwell. This deterioration was multifactorial, with acute decompensated heart failure alongside COVID-19. After multidisciplinary discussion, she was considered too unwell for surgery and palliated.

Oncoplastic breast surgery: the role of negative pressure wound therapy.

Wound-related problems following breast surgery are common. Delayed wound healing can lead to poor cosmesis and, among breast cancer patients, can result in delays in receiving adjuvant treatment. The aim of our review was to look at the literature in relation to the role of negative pressure wound therapy in oncoplastic breast surgery, as at the time of writing, there is no consensus on the use of prophylactic negative pressure dressings in closed wounds following breast surgery.

HIV Drugs Inhibit Transfer of Plasmids Carrying Extended-Spectrum ß-Lactamase and Carbapenemase Genes.

Antimicrobial-resistant (AMR) infections pose a serious risk to human and animal health. A major factor contributing to this global crisis is the sharing of resistance genes between different bacteria via plasmids. The WHO lists Enterobacteriaceae, such as Escherichia coli and Klebsiella pneumoniae, producing extended-spectrum ß-lactamases (ESBL) and carbapenemases as "critical" priorities for new drug development. These resistance genes are most often shared via plasmid transfer. However, finding methods to prevent resistance gene sharing has been hampered by the lack of screening systems for medium-/high-throughput approaches. Here, we have used an ESBL-producing plasmid, pCT, and a carbapenemase-producing plasmid, pKpQIL, in two different Gram-negative bacteria, E. coli and K. pneumoniae Using these critical resistance-pathogen combinations, we developed an assay using fluorescent proteins, flow cytometry, and confocal microscopy to assess plasmid transmission inhibition within bacterial populations in a medium-throughput manner. Three compounds with some reports of antiplasmid properties were tested; chlorpromazine reduced transmission of both plasmids and linoleic acid reduced transmission of pCT. We screened the Prestwick library of over 1,200 FDA-approved drugs/compounds. From this, we found two nucleoside analogue drugs used to treat HIV, abacavir and azidothymidine (AZT), which reduced plasmid transmission (AZT, e.g., at 0.25 µg/ml reduced pCT transmission in E. coli by 83.3% and pKpQIL transmission in K. pneumoniae by 80.8% compared to untreated controls). Plasmid transmission was reduced by concentrations of the drugs which are below peak serum concentrations and are achievable in the gastrointestinal tract. These drugs could be used to decolonize humans, animals, or the environment from AMR plasmids.IMPORTANCE More and more bacterial infections are becoming resistant to antibiotics. This has made treatment of many infections very difficult. One of the reasons this is such a large problem is that bacteria are able to share their genetic material with other bacteria, and these shared genes often include resistance to a variety of antibiotics, including some of our drugs of last resort. We are addressing this problem by using a fluorescence-based system to search for drugs that will stop bacteria from sharing resistance genes. We uncovered a new role for two drugs used to treat HIV and show that they are able to prevent the sharing of two different types of resistance genes in two unique bacterial strains. This work lays the foundation for future work to reduce the prevalence of resistant infections.

Transitioning to a general practice placement for the foundation doctor.

Time spent training in general practice can be highly beneficial for junior doctors irrespective of their future specialty choice. A large number of foundation year two doctors from the United Kingdom will undertake time in general practice as part of the compulsory Foundation Programme for new medical graduates following recommendations for all such rotations to include a community placement. For the majority, this will be their first time working in primary care post-qualification and this role will bring significant new clinical and professional challenges. In this article we give thirty points of advice for foundation doctors starting a general practice rotation and additional insight for their clinical supervisors, grouped into clinical, consultation related and general points, as informed by the authors' experience and an electronic survey of foundation doctors and general practice trainers.

Rapid Discharge to Home After Total Knee Arthroplasty Is Safe in Eligible Medicare Patients.

BACKGROUND: This study was aimed at assessing the risk of readmission for Medicare patients discharged home within a day of total knee arthroplasty (TKA) compared to those discharged on day 2 or beyond in a community medical center. METHODS: A hospital inpatient database was queried for all unilateral, primary TKAs performed on patients 65 years or older from January 1, 2013, to December 31, 2015. A total of 2287 patients met the study criteria, of which 1502 were discharged within a day (short stay), and 785 were discharged on day 2 or beyond (traditional stay). The main outcome measures were all-cause 30-day and unplanned 90-day readmissions. RESULTS: Short-stay patients did not experience a higher 30-day readmission rate (1.1%) compared to the traditional-stay patients (2.7%), nor did they experience a higher rate of unplanned 90-day readmissions (1.7% vs 3.6%). The short-stay group had more favorable demographics compared to the traditional-stay group. Logistic regression results revealed that none of the demographic factors considered had a statistically significant impact on 30-day readmission odds for either group. For unplanned 90-day readmissions, the results showed that for the short-stay patients, with the exception of age, none of the other demographic factors had significant impact on readmission odds and none were significant for the traditional-stay group. CONCLUSION: Our results suggest that the Medicare patients meeting discharge criteria and discharged home within a day of TKA do not have an increased risk of 30-day and 90-day readmission.

The AAHKS Clinical Research Award: Liposomal Bupivacaine and Periarticular Injection Are Not Superior to Single-Shot Intra-articular Injection for Pain Control in Total Knee Arthroplasty.

BACKGROUND: Intraoperative injections can help reduce early postoperative pain in total knee arthroplasty. We proposed that liposomal bupivacaine would not be superior to more common and cheaper injections. METHODS: A single-blinded prospective randomized study with 207 consecutive patients was completed. Patients were randomized to treatment with periarticular liposomal bupivacaine injection, periarticular injection of bupivacaine/morphine, or intra-articular injection of bupivacaine/morphine at the conclusion of the procedure. Postoperative visual analog pain scores and narcotic consumption were recorded and analyzed. RESULTS: There was no significant difference in postoperative visual analog pain scores or narcotic consumption among the 3 study groups. CONCLUSION: Intra-articular injection of bupivacaine and morphine is as effective for postoperative pain control in total knee arthroplasty as periarticular bupivacaine/morphine injection and liposomal bupivacaine. Use of liposomal bupivacaine in total knee arthroplasty is costly and not justified.

An Algorithmic, Pie-Crusting Medial Soft Tissue Release Reduces the Need for Constrained Inserts Patients With Severe Varus Deformity Undergoing Total Knee Arthroplasty.

BACKGROUND: We studied the need to use a constrained insert for residual intraoperative instability and the 1-year result of patients undergoing total knee arthroplasty (TKA) for a varus deformity. In a control group, a "classic" subperiosteal release of the medial soft tissue sleeve was performed as popularized by pioneers of TKA. In the study group, an algorithmic approach that selectively releases and pie-crusts posteromedial structures in extension and anteromedial structures in flexion was used. METHODS: All surgeries were performed by a single surgeon using measured resection technique, and posterior-stabilized, cemented implants. There were 228 TKAs in the control group and 188 in the study group. Outcome variables included the use of a constrained insert, and the Knee Society Score at 6 weeks, 4 months, and 1 year postoperatively. The effect of the release technique on use of constrained inserts and clinical outcomes were analyzed in a multivariate model controlling for age, sex, body mass index, and severity of deformity. RESULTS: The use of constrained inserts was significantly lower in study than in control patients (8% vs 18%; P = .002). There was no difference in the Knee Society Score and range of motion between the groups at last follow-up. No patient developed postoperative medial instability. CONCLUSION: This algorithmic, pie-crusting release technique resulted in a significant reduction in the use of constrained inserts with no detrimental effects in clinical results, joint function, and stability. As constrained TKA implants are more costly than nonconstrained ones, if the adopted technique proves to be safe in the long term, it may cause a positive shift in value for hospitals and cost savings in the health care system.

Posterior reversible encephalopathy syndrome following an inadvertent dural puncture during an emergency laparotomy for ischemic colitis - a case report.

Posterior reversible encephalopathy syndrome (PRES) is a clinico-neuroradiological syndrome characterized by various symptoms of neurological disease. It has commonly been reported in association with acute hypertension, pre-eclampsia, eclampsia, sepsis, and exposure to immunosuppressants. Here, we report on a normotensive woman who developed a severe frontal headache, visual disturbances, and hypertension 3 days after undergoing an emergency laparotomy for ischemic colitis during which she suffered an inadvertent dural puncture. Neuro-imaging revealed features consistent with PRES. The patient went on to make a good recovery, being discharged 21 days postoperatively, with only minor visual disturbances and memory problems. This case highlights the importance of awareness of PRES to all specialties. On reviewing the literature, we feel that PRES may be a potential differential diagnosis to post-procedural neurological symptoms in those patients undergoing routine procedures such as spinal anesthetics or lumbar punctures.

Effect of proximal femoral bone support on the fixation of a press-fit noncemented total hip replacement femoral component.

PURPOSE: Proximal femoral bone loss is a common challenge in revision hip arthroplasty. In this study, in-vitro fixation of a non-cemented, rectangular, dual-tapered, press-fit femoral component designed to achieve metadiaphyseal fixation was analyzed using an accelerated proximal femoral bone loss model to assess the potential use in revision cases. METHODS: The press-fit AlloclassicTM femoral stem was implanted in ten cadaveric femurs and tested under cyclic biomechanical loading in an intact state, and then again after sequential proximal femoral bone resections, simulating increasing amounts of bone deficiency. Anterior-posterior and medial-lateral interface motions were measured at the distal stem tip throughout loading. 
 RESULTS: Three specimens remained stable throughout testing, with initial and peak per-cycle motions of less than 50 µm. Six specimens were destabilized under loading with higher per-cycle motions, specifically at the distal stem tip during peak loading in the anterior-posterior direction, with motions of 78±69 µm, compared to 12±9 µm in the stable specimens (P<.05). Total migration of the destabilized specimens was also significantly higher, specifically at the proximal stem tip in the medial-lateral direction, with migrations of 101±34 µm (P<.05) and at the distal stem tip in the anterior-posterior direction, with migrations of 155±179 µm (P<.05), compared to 33±12 µm and 13±11 µm for the stable specimens. CONCLUSION: The results indicate that when strong initial fixation is achieved, long-term success is possible given substantial proximal femoral bone loss.

Death after closed adolescent knee injury and popliteal artery occlusion: a case report and clinical review.

A healthy adolescent male soccer player sustained a radiograph-negative, effusion-negative physeal injury of the proximal tibia from a ground-level fall with traumatic occlusion of the popliteal artery. Orthopaedic evaluation and arteriography were delayed for 72 hours after the injury. He arrived at a tertiary referral center in multisystem organ failure secondary to lower extremity ischemic necrosis, septic pulmonary thromboembolism, and systemic shock. Emergent medical evaluation, a high index of suspicion, and a careful neurovascular examination are imperative after every closed knee injury in the young athlete.

Effects of 7 days of arginine-alpha-ketoglutarate supplementation on blood flow, plasma L-arginine, nitric oxide metabolites, and asymmetric dimethyl arginine after resistance exercise.

BACKGROUND: Arginine-alpha-ketoglutarate (AAKG) supplements are alleged to increase nitric oxide production, thereby resulting in vasodilation during resistance exercise. This study sought to determine the effects of AAKG supplementation on hemodynamics and brachial-artery blood flow and the circulating levels of L-arginine, nitric oxide metabolites (NOx; nitrate/nitrite), asymmetric dimethyl arginine (ADMA), and L-arginine:ADMA ratio after resistance exercise. METHODS: Twenty-four physically active men underwent 7 days of AAKG supplementation with 12 g/day of either NO(2) Platinum or placebo (PLC). Before and after supplementation, a resistance-exercise session involving the elbow flexors was performed involving 3 sets of 15 repetitions with 70-75% of 1-repetition maximum. Data were collected immediately before, immediately after (PST), and 30 min after (30PST) each exercise session. Data were analyzed with factorial ANOVA (p < .05). RESULTS: Heart rate, blood pressure, and blood flow were increased in both groups at PST (p = .001) but not different between groups. Plasma L-arginine was increased in the NO(2) group (p = .001). NOx was shown to increase in both groups at PST (p = .001) and at 30PST (p = .001) but was not different between groups. ADMA was not affected between tests (p = .26) or time points (p = .31); however, the L-arginine:ADMA ratio was increased in the NO(2) group (p = .03). CONCLUSION: NO(2) Platinum increased plasma L-arginine levels; however, the effects observed in hemodynamics, brachial-artery blood flow, and NOx can only be attributed to the resistance exercise.

Challenges to bone formation in spinal fusion.

Spinal arthrodesis continues to expand in clinical indications and surgical practice. Despite a century of study, failure of bone formation or pseudarthrosis can occur in individual patients with debilitating clinical symptoms. Here we review biological and technical aspects of spinal fusion under active investigation, describe relevant biomechanics in health and disease, and identify the possibilities and limitations of translational animal models. The purpose of this article is to foster collaborative efforts with researchers who model bone hierarchy. The induction of heterotopic osteosynthesis requires a complex balance of biologic factors and operative technique to achieve successful fusion. Anatomical considerations of each spinal region including blood supply, osteology, and biomechanics predispose a fusion site to robust or insufficient bone formation. Careful preparation of the fusion site and appropriate selection of graft materials remains critical but is sometimes guided by conflicting evidence from the long-bone literature. Modern techniques of graft site preparation and instrumentation have evolved for every segment of the vertebral column. Despite validated biomechanical studies of modern instrumentation, a correlation with superior clinical outcomes is difficult to demonstrate. In many cases, adjuvant biologic therapies with allograft and synthetic cages have been used successfully to reproduce the enhancement of fusion rates observed with cancellous and tricortical autograft. Current areas of investigation comprise materials science, stem cell therapies, recombinant growth factors, scaffolds and biologic delivery systems, and minimally invasive surgical techniques to optimize the biologic response to intervention. Diverse animal models are required to approach the breadth of spinal pathology and novel therapeutics.

Static and dynamic gait parameters before and after multilevel soft tissue surgery in ambulating children with cerebral palsy.

BACKGROUND: Recent studies have questioned the efficacy of releasing hip flexion contractures and the resulting ankle position after tendoachilles lengthening in ambulating children with cerebral palsy (CP). METHODS: Twenty-three ambulatory children with CP underwent 96 soft tissue-lengthening procedures without bony surgery. Preoperative and postoperative clinical and computerized gait data were reviewed. RESULTS: Static contractures improved reliably, with improvements in all areas measured, including hip flexion contracture (14 degree improvement), hip abduction (19 degree improvement), popliteal angle (26 degree improvement), and ankle dorsiflexion (11 degree improvement). The changes in computerized gait data were less uniform. The knees showed significant benefits, as evidenced by improved maximal knee extension in stance phase (37.3 degree preop and 19.9 degree postop) and at initial contact (51.6 degree preop and 34.8 degree postop). At the hip, a statistically significant improvement was only seen in maximum hip extension in stance phase (minimum hip flexion), and the magnitude of this change was only 4.6 degree (15.3 to 10.7 degree). There were no significant changes at the pelvis. At the ankle, the tendency was toward calcaneal gait after Achilles tendon lengthening, with excessive dorsiflexion seen both in stance (17.3 degree) and at toe off (-6.9 degree). Tempero-spatial parameters showed improved stride length, but no significant changes in gait velocity or cadence. DISCUSSION: The persistence of crouch postoperatively, though improved, likely limited the potential changes in hip kinematics. As this study excluded patients undergoing osseous surgery, it is possible that lever arm dysfunction may have contributed to the ongoing crouch. The results of this study suggest that static contractures and knee kinematics improve reliably after soft tissue surgery in children with CP, but that caution must be exercised when considering heel cord lengthening in these children. LEVEL OF EVIDENCE: Therapeutic level II. See Instructions to Authors for a complete description of levels of evidence.

Variola virus immune evasion proteins.

Variola virus, the causative agent of smallpox, encodes approximately 200 proteins. Over 80 of these proteins are located in the terminal regions of the genome, where proteins associated with host immune evasion are encoded. To date, only two variola proteins have been characterized. Both are located in the terminal regions and demonstrate immunoregulatory functions. One protein, the smallpox inhibitor of complement enzymes (SPICE), is homologous to a vaccinia virus virulence factor, the vaccinia virus complement-control protein (VCP), which has been found experimentally to be expressed early in the course of vaccinia infection. Both SPICE and VCP are similar in structure and function to the family of mammalian complement regulatory proteins, which function to prevent inadvertent injury to adjacent cells and tissues during complement activation. The second variola protein is the variola virus high-affinity secreted chemokine-binding protein type II (CKBP-II, CBP-II, vCCI), which binds CC-chemokine receptors. The vaccinia homologue of CKBP-II is secreted both early and late in infection. CKBP-II proteins are highly conserved among orthopoxviruses, sharing approximately 85% homology, but are absent in eukaryotes. This characteristic sets it apart from other known virulence factors in orthopoxviruses, which share sequence homology with known mammalian immune regulatory gene products. Future studies of additional variola proteins may help illuminate factors associated with its virulence, pathogenesis and strict human tropism. In addition, these studies may also assist in the development of targeted therapies for the treatment of both smallpox and human immune-related diseases.