Trichosporon asahii opportunistic pneumonia after a severe COVID-19 infection.

This is the first reported case of fatal opportunistic Trichosporon asahii pneumonia in the setting of severe COVID-19 pneumonia. The patient had ventilator-requiring respiratory failure secondary to COVID-19 infection. The patient received intravenous broad-spectrum antibiotics, tocilizumab, and corticosteroids with subsequent development of cavitary infiltrates. Bronchoalveolar lavage grew T. asahii. We describe a rare complication of COVID-19 infection and describe the microbial diagnosis, possible mechanism of infection, and optimal treatment.

Beta blockers in critically ill patients with traumatic brain injury: Results from a multicenter, prospective, observational American Association for the Surgery of Trauma study.

BACKGROUND: Beta blockers, a class of medications that inhibit endogenous catecholamines interaction with beta adrenergic receptors, are often administered to patients hospitalized after traumatic brain injury (TBI). We tested the hypothesis that beta blocker use after TBI is associated with lower mortality, and secondarily compared propranolol to other beta blockers. METHODS: The American Association for the Surgery of Trauma Clinical Trial Group conducted a multi-institutional, prospective, observational trial in which adult TBI patients who required intensive care unit admission were compared based on beta blocker administration. RESULTS: From January 2015 to January 2017, 2,252 patients were analyzed from 15 trauma centers in the United States and Canada with 49.7% receiving beta blockers. Most patients (56.3%) received the first beta blocker dose by hospital day 1. Those patients who received beta blockers were older (56.7 years vs. 48.6 years, p < 0.001) and had higher head Abbreviated Injury Scale scores (3.6 vs. 3.4, p < 0.001). Similarities were noted when comparing sex, admission hypotension, mean Injury Severity Score, and mean Glasgow Coma Scale. Unadjusted mortality was lower for patients receiving beta blockers (13.8% vs. 17.7%, p = 0.013). Multivariable regression determined that beta blockers were associated with lower mortality (adjusted odds ratio, 0.35; p < 0.001), and propranolol was superior to other beta blockers (adjusted odds ratio, 0.51, p = 0.010). A Cox-regression model using a time-dependent variable demonstrated a survival benefit for patients receiving beta blockers (adjusted hazard ratio, 0.42, p < 0.001) and propranolol was superior to other beta blockers (adjusted hazard ratio, 0.50, p = 0.003). CONCLUSION: Administration of beta blockers after TBI was associated with improved survival, before and after adjusting for the more severe injuries observed in the treatment cohort. This study provides a robust evaluation of the effects of beta blockers on TBI outcomes that supports the initiation of a multi-institutional randomized control trial. LEVEL OF EVIDENCE: Therapeutic/care management, level III.

Transcriptional landscape of epithelial and immune cell populations revealed through FACS-seq of healthy human skin.

Human skin consists of multiple cell types, including epithelial, immune, and stromal cells. Transcriptomic analyses have previously been performed from bulk skin samples or from epithelial and immune cells expanded in cell culture. However, transcriptomic analysis of bulk skin tends to drown out expression signals from relatively rare cells while cell culture methods may significantly alter cellular phenotypes and gene expression profiles. To identify distinct transcriptomic profiles of multiple cell populations without substantially altering cell phenotypes, we employed a fluorescence activated cell sorting method to isolate keratinocytes, dendritic cells, CD4+ T effector cells, and CD8+ T effector cells from healthy skin samples, followed by RNA-seq of each cell population. Principal components analysis revealed distinct clustering of cell types across samples, while differential expression and coexpression network analyses revealed transcriptional profiles of individual cell populations distinct from bulk skin, most strikingly in the least abundant CD8+ T effector population. Our work provides a high resolution view of cutaneous cellular gene expression and suggests that transcriptomic profiling of bulk skin may inadequately capture the contribution of less abundant cell types.

Anti-nerve growth factor in pain management: current evidence.

There continues to be an unmet need for safe and effective pain medications. Opioids and nonsteroidal anti-inflammatory drugs (NSAIDs) dominate the clinical landscape despite limited effectiveness and considerable side-effect profiles. Although significant advancements have identified myriad potential pain targets over the past several decades, the majority of new pain pharmacotherapies have failed to come to market. The discovery of nerve growth factor (NGF) and its interaction with tropomyosin receptor kinase A (trkA) have been well characterized as important mediators of pain initiation and maintenance, and pharmacotherapies targeting this pathway have the potential to be considered promising methods in the treatment of a variety of nociceptive and neuropathic pain conditions. Several methodologic approaches, including sequestration of free NGF, prevention of NGF binding and trkA activation, and inhibition of trkA function, have been investigated in the development of new pharmacotherapies. Among these, NGF-sequestering antibodies have exhibited the most promise in clinical trials. However, in 2010, reports of rapid joint destruction leading to joint replacement prompted the US Food and Drug Administration (FDA) to place a hold on all clinical trials involving anti-NGF antibodies. Although the FDA has since lifted this hold and a number of new trials are under way, the long-term efficacy and safety profile of anti-NGF antibodies are yet to be established.

Failed pneumoperitoneum for laparoscopic surgery following autologous Deep Inferior Epigastric Perforator (DIEP) flap breast reconstruction: a case report.

BACKGROUND: Laparoscopic abdominal surgery may prove difficult in patients who have undergone previous abdominal procedures. No reports in the medical literature have presented an aborted laparoscopic procedure for failed pneumoperitoneum following autologous flap-based breast reconstruction. CASE PRESENTATION: A 55-year-old woman presented with recurrent invasive lobular carcinoma of the right breast as well as a history of ductal carcinoma in situ of the left breast. The patient desired to proceed with bilateral skin- and nipple-sparing mastectomies with right axillary lymph node biopsy, followed by immediate bilateral autologous deep inferior epigastric perforator (DIEP) flap-based breast reconstruction. Preoperatively, a computerized tomography angiogram was obtained for reconstructive preparation, which revealed a left adrenal mass. Ensuing work-up diagnosed a pheochromocytoma. Given the concern for breast cancer progression, the patient elected to proceed first with breast cancer surgery and reconstruction prior to addressing the adrenal tumor. Subsequently, 3 months later the patient was brought to the operating room for a laparoscopic left adrenalectomy for the pheochromocytoma. With complete pharmacologic abdominal relaxation, the abdomen proved too tight to accommodate sufficient pneumoperitoneum and the laparoscopy was aborted. The patient was evaluated in the outpatient setting for assessment of abdominal wall compliance at regular intervals. Five months later, the patient was taken back to the operating room where pneumoperitoneum was established without difficulty and the laparoscopic left adrenalectomy was performed without complications. CONCLUSION: Pneumoperitoneum for laparoscopic surgery subsequent to autologous DIEP flap-based breast reconstruction may prove difficult as a result of loss of abdominal wall compliance. Prior to performing laparoscopy in such patients, surgeons should consider the details of the patient's previous reconstructive procedure and assess potential risk factors for difficulty with insufflation. Lastly, careful abdominal examination should be performed to indicate whether laparoscopy for elective procedures should be delayed until abdominal wall compliance normalizes.

Assessing Emergency Preparedness and Response Capacity Using Community Assessment for Public Health Emergency Response Methodology: Portsmouth, Virginia, 2013.

OBJECTIVE: For the past decade, emergency preparedness campaigns have encouraged households to meet preparedness metrics, such as having a household evacuation plan and emergency supplies of food, water, and medication. To estimate current household preparedness levels and to enhance disaster response planning, the Virginia Department of Health with remote technical assistance from the Centers for Disease Control and Prevention conducted a community health assessment in 2013 in Portsmouth, Virginia. METHODS: Using the Community Assessment for Public Health Emergency Response (CASPER) methodology with 2-stage cluster sampling, we randomly selected 210 households for in-person interviews. Households were questioned about emergency planning and supplies, information sources during emergencies, and chronic health conditions. RESULTS: Interview teams completed 180 interviews (86%). Interviews revealed that 70% of households had an emergency evacuation plan, 67% had a 3-day supply of water for each member, and 77% had a first aid kit. Most households (65%) reported that the television was the primary source of information during an emergency. Heart disease (54%) and obesity (40%) were the most frequently reported chronic conditions. CONCLUSIONS: The Virginia Department of Health identified important gaps in local household preparedness. Data from the assessment have been used to inform community health partners, enhance disaster response planning, set community health priorities, and influence Portsmouth's Community Health Improvement Plan.

Emerging targets in treating pain.

PURPOSE OF REVIEW: To provide an overview on drug targets and emerging pharmacological treatment options for chronic pain. RECENT FINDINGS: Chronic pain poses an enormous socioeconomic burden for the more than 30% of people who suffer from it, costing over $600 billion per year in the USA. In recent years, there has been a surge in preclinical and clinical research endeavors to try to stem this epidemic. Preclinical studies have identified a wide array of potential targets, with some of the most promising translational research being performed on novel opioid receptors, cannabinoid receptors, selective ion channel blockers, cytokine inhibitors, nerve growth factor inhibitors, N-methyl-D-aspartate receptor antagonists, glial cell inhibitors, and bisphosphonates. SUMMARY: There are many obstacles for the development of effective medications to treat chronic pain, including the inherent challenges in identifying pathophysiological mechanisms, the overlap and multiplicity of pain pathways, and off-target adverse effects stemming from the ubiquity of drug target receptor sites and the lack of highly selective receptor ligands. Despite these barriers, the number and diversity of potential therapies have continued to grow, to include disease-modifying and individualized drug treatments.

A multi-disciplinary approach to the management of fungal osteomyelitis: current concepts in post-traumatic lower extremity reconstruction: a case report.

Limb salvage in fungal osteomyelitis of the post-traumatic lower extremity represents a difficult clinical problem requiring aggressive management. We report lower extremity salvage by radical bony debridement, free tissue transfer, distraction osteogenesis with bone-docking, and a novel antifungal regimen in a clinical setting of infection with Scedosporium inflatum, historically requiring amputation in 100% of cases. We treated Scedosporium inflatum osteomyelitis of the tibia and calcaneus with radical debridement of infected bone, free partial medial rectus abdominis muscle flap coverage, transport distraction osteogenesis, and combination voriconazole/terbinafine chemotherapy, a novel antifungal regimen. We achieved successful control of the infection, limb salvage, and an excellent functional outcome through aggressive debridement of infected bone and soft tissue, elimination of dead space within the bony defect, the robust perfusion provided by the free flap, the hypervascular state induced by distraction osteogenesis, and the synergism of the novel antifungal regimen.

Surgical treatment options for subacute ischemia of the hand: case report and literature review.

PURPOSE: The most effective surgical approach to the treatment of digital ischemia has not yet been established. The purpose of this study is to review currently accepted options for revascularization in acute and chronic settings of digital ischemia, and to augment this discussion by describing the approach of our surgical team in a unique case of subacute ischemia. OPERATIVE TECHNIQUE: To restore blood flow to a patient's ischemic hand, we performed a microvascular reconstruction, using a reverse interpositional vein graft with 3 anastomoses: the ulnar artery was used for inflow and the superficial palmar arch and the common digital artery were used for outflow. RESULTS: The patient experienced immediate postoperative pain relief. Blood flow was restored, which prevented digital amputation. The graft remained patent at 18 months' follow-up and the patient exhibited normal motor and sensory function. CONCLUSIONS: Surgical reconstruction of the hand is a viable treatment option for carefully selected patients presenting with subacute digital ischemia. Other medical and surgical techniques have been described in the recent literature, but further study is needed to determine the long-term success of newer microsurgical interventions.

Implantable venous Doppler monitoring in head and neck free flap reconstruction increases the salvage rate.

BACKGROUND: Free flap success depends on rapid identification and subsequent salvage of failing flaps. Conventional free flap monitoring techniques require an external component, whereas an implantable monitor readily indicates changes in free flap perfusion, especially in buried flaps used in head and neck reconstruction. METHODS: This is a retrospective review of 169 consecutive head and neck free flaps reconstructed mostly for oncologic surgical defects in 155 patients from April of 2000 to December of 2006, all of which were monitored by an implantable venous Doppler device. RESULTS: There were 25 buried flaps, representing 14.8 percent of 169 flaps. Flap ischemia caused by thrombosis (n = 16), hematoma (n = 2), or tight closure (n = 1) occurred in 11.2 percent of the cases. The Doppler probe detected all of the failing free flaps, and we were able to salvage 18 of 19 ischemic flaps (94.7 percent). All Doppler-detected ischemic nonburied flaps (100 percent) and three of the four buried free flaps were salvaged (75 percent). There were 33 total complications (19.5 percent), with thrombosis occurring in 9.5 percent of the flaps, whereas 12 flaps required reoperation for vascular revision (7.1 percent). The mortality rate was less than 1 percent (0.6 percent). The overall success rate using the implantable Doppler probe was 98.2 percent, which was similar to that of the most recent reported cases of all free flaps in the literature, with significant improvement in the salvage rate for both buried and nonburied head and neck free flaps. CONCLUSION: The implantable Doppler probe is a useful monitoring device in buried free flaps and should be considered for use in head and neck reconstruction.

Sagittal whole-spine magnetic resonance imaging in 750 consecutive outpatients: accurate determination of the number of lumbar vertebral bodies.

OBJECT: When the number of lumbar and sacral vertebrae is being assessed, variations from typical lumbosacral anatomy may confuse the practitioner, potentially leading to significant clinical errors. In this study, the authors describe the statistical variation in lumbar spine anatomy in an outpatient imaging setting, evaluate the potential implications for clinical practice based on the variation in the number of lumbar-type vertebrae identified, and recommend a method for rapidly determining the number of lumbar spine vertebral bodies (VBs) in outpatients referred for lumbar spine MR imaging. METHODS: A total of 762 patients (male and female) who presented with low back-related medical conditions underwent whole-spine MR imaging in an outpatient setting. RESULTS: The high-speed whole-spine evaluation was successful for determining the number of lumbar-type VBs in 750 (98%) of 762 consecutive patients. The sagittal whole-spine 3-T MR imaging system images obtained between the beginning of January 2005 and the end of February 2007 were reviewed. The VBs were counted successively from the level of C-2 inferiorly to the intervertebral disc below the most inferior lumbar-type VB. Numbers of disc herniations were also evaluated in the context of the number of VBs. CONCLUSIONS: One in 5 of these outpatients did not have 5 lumbar-type vertebrae: 14.5% had 6; 5.3% had 4; and 1 (0.13%) had the rare finding of 3 lumbar-type vertebrae. Two-thirds of the individuals with 6 lumbar-type vertebrae were male and two-thirds of the individuals with 4 lumbar-type vertebrae were female. Sagittal whole-spine MR imaging can be performed rapidly and efficiently in the majority of patients (98%), and provides improved accuracy for the determination of the number of lumbar-type VBs. A supplementary coronal MR, Ferguson view radiograph or intraoperative fluoroscopic determination for the presence of lumbosacral transitional vertebrae may add additional information when indicated for clinical treatment or surgical planning.

Open incisional hernia repair at an academic tertiary care medical center.

OBJECTIVE: To describe the postoperative complication rates of a large consecutive series of patients who underwent open incisional ventral hernia repair. DESIGN: Retrospective medical record review of an accumulated database. SETTING: University tertiary care medical center. PATIENTS: All patients who underwent open incisional ventral hernia repair from March 1, 2003, through February 28, 2008. INTERVENTION: Open incisional ventral hernia repair. MAIN OUTCOME MEASURES: Postoperative complications, including hernia recurrences. RESULTS: A total of 507 cases (465 patients; female to male ratio, 1.1:1) met our criteria; median follow-up was 40 months. In 23.5% of the cases, repair had been attempted previously, and 16.4% had previously undergone organ transplant. The postoperative complication rate was 38.1%. Hernias recurred in 18.9% of cases. Perioperative mortality was 1.0%. Patients undergoing transplant were more likely than those not undergoing transplant to have a hernia recurrence (16.3% vs 32.5%; P < .001) and were equally likely to have a postoperative complication (36.9% vs 44.6%; P = .19). Patients who underwent repair of a recurrent incisional hernia were as likely to have a hernia recurrence as those who underwent initial repair (21.0% vs 18.3%; P = .52) but more likely to have an overall complication (47.9% vs 35.1%; P = .01). CONCLUSIONS: In this series of incisional hernia repairs at a tertiary care center, the overall recurrence rate of 18.9% is comparable to that of other published series. Ours is the largest published series of recurrent hernias that shows a recurrence rate comparable to that for initial repairs. This outcome may be the result of greater use of more complex repair techniques.

The error of omission: a simple checklist approach for improving operating room safety.

SUMMARY: The primary goal of patient safety must go hand in hand with the goal of producing reliably good aesthetic and functional results. The implementation of a proactive checklist improves operating room communication and takes the necessary step toward reducing the often neglected errors of omission. These steps are necessary if we are to ultimately achieve our goal of improving safety comprehensively in the operating room.

Management of benign tumors of the adolescent breast.

LEARNING OBJECTIVES: After studying this article, the participant should be able to: 1. Describe the differential diagnosis of breast tumors in adolescent girls. 2. Compare and contrast surgical options for the management of adolescent breast tumors. 3. Recognize the utility of a reduction mammaplasty technique when resecting these larger tumors in adolescents. SUMMARY: Although 99 percent of breast lesions in female adolescents are benign tumors, surgical intervention is commonly required. This article reviews the differential diagnosis, evaluation, and management of these benign tumors. A modified surgical technique for resection of large fibroadenomas and reconstruction of the remaining breast is described. The authors review the approach to five specific breast lesions: fibroadenomas, phyllodes tumors, juvenile hypertrophy, inflammatory processes, and premature breast development.

Vacuum-assisted closure for fasciotomy wounds following compartment syndrome of the leg.

This study evaluated the efficacy of vacuum-assisted closure (VAC) for treatment of fasciotomy wounds for traumatic compartment syndrome. The authors reviewed the records of a consecutive series of 34 patients who had compartment syndrome of the leg requiring the standard two-incision release of all four compartments and received the application of VAC therapy until the time of definitive wound closure or coverage. A matched series of 34 consecutive antecedent patients with the same entry criteria, except for the use of the VAC, were also studied and served as a control group. The main parameter of interest was the time to "definitive closure" (delayed primary closure with sutures or skin graft coverage) of the wounds. Of the 68 wounds in 34 patients managed with VAC, the average time to definitive closure for both the lateral and the medial wounds was 6.7 days. For the 70 wounds in the 34 control patients, the average time to definitive closure was 16.1 days. This difference in time to wound closure between the VAC group and the non-VAC group was statistically significant (p < .05). Subatmospheric treatment for compartment syndrome of the leg after fasciotomy theoretically helps to speed the resolution of the swelling and tissue edema that are often components of this clinical entity. Experimental work has shown vacuum-assisted wound management to be effective in hastening the resolution of wound edema, enhancing local blood flow, promoting granulation tissue, and thwarting bacterial colonization. These factors may account for its utility in the management of fasciotomy wounds in the setting of compartment syndrome of the leg.

The effect of gradual or acute arterial occlusion on skeletal muscle blood flow, arteriogenesis, and inflammation in rat hindlimb ischemia.

BACKGROUND: Current experimental models of critical limb ischemia are based on acute ischemia rather than on chronic ischemia. Human peripheral vascular disease is largely a result of chromic ischemia. We hypothesized that a model of chronic hindlimb ischemia would develop more collateral arteries, more blood flow, and less necrosis and inflammation than would acute hindlimb ischemia. We therefore developed a rat model of chronic hindlimb ischemia and compared the effects of chronic ischemia with those of acute ischemia on hindlimb skeletal muscle. METHODS: Acute or chronic ischemia was induced in 36 male Sprague-Dawley rats. Chronic ischemia caused blood flow, as measured by laser Doppler scanning and confirmed by muscle oxygen tension measurements, to gradually decrease over 1 to 2 weeks after operation. RESULTS: Histologic analysis showed chronic hindlimb ischemia better preserved muscle mass and architecture and stimulated capillary angiogenesis, while lacking the muscle necrosis and inflammatory cell infiltrate seen after acute ischemia. Surprisingly, the chronic ischemia group recovered dermal blood flow more slowly and less completely than did the acute ischemia group, as measured by laser Doppler (0.66 +/- 0.02 vs 0.76 +/- 0.04, P < .05) and tissue oxygen tension (0.61 +/- 0.06 vs 0.81 +/- 0.05, P < .05) at 40 days postoperatively. Consistent with poorer blood flow recovery, chronic ischemia resulted in smaller diameter collateral arteries (average diameter of the five largest collaterals on angiogram was 0.01 +/- 0.0003 mm vs 0.013 +/- 0.0007 mm for acute, P < .005 at 40 days postoperatively). Acute ischemia resulted in decreased tissue concentrations of vascular endothelial growth factor (VEGF) (0.96 +/- 0.23 pg/mg of muscle for acute vs 4.4 +/- 0.75 and 4.8 +/- 0.75 pg/mg of muscle for unoperated and chronic, respectively, P < .05 acute vs unoperated), and in increased tissue concentrations of interleukin (IL)-1beta (7.3 +/- 4.0 pg/mg of muscle for acute vs undetectable and 1.7 +/- 1.6 pg/mg of muscle for unoperated and chronic, respectively, P < 0.05 acute vs unoperated). CONCLUSIONS: We describe here the first model of chronic hindlimb ischemia in the rat. Restoration of blood flow after induction of hindlimb ischemia is dependent on the rate of arterial occlusion. This difference in blood flow recovery correlates with distinct patterns of muscle necrosis, inflammatory cell infiltration, and cytokine induction in the ischemic muscle. Differences between models of acute and chronic hindlimb ischemia may have important consequences for future studies of mechanisms regulating arteriogenesis and for therapeutic approaches aimed at promoting arteriogenesis in humans suffering from critical limb ischemia. CLINICAL RELEVANCE: Despite the substantial clinical differences between acute and chronic ischemia, researchers attempting to develop molecular therapies to treat critical limb ischemia have only tested those therapies in experimental models of acute hindlimb ischemia. We present here a novel model of chronic hindlimb ischemia in the rat. We further demonstrate that when hindlimb ischemia is developed chronically, collateral artery development is poorer than when hindlimb ischemia is developed acutely. These findings suggest that further tests of molecular therapies for critical limb ischemia should be performed in chronic hindlimb ischemia models rather than in acute hindlimb ischemia models.