To flip or not: Case series of coronary angioplasty in patients with right-sided heart.

Coronary angioplasty in patients with a right-sided heart may be difficult due to challenges in engaging the coronary arteries, interpreting angiogram, and further delivering intracoronary therapies. We present our experience of percutaneous coronary intervention in two cases and propose a practical algorithm to approach cardiac catheterization in these patients.

Prediction of pKa Using Machine Learning Methods with Rooted Topological Torsion Fingerprints: Application to Aliphatic Amines.

The acid-base dissociation constant, pKa, is a key parameter to define the ionization state of a compound and directly affects its biopharmaceutical profile. In this study, we developed a novel approach for pKa prediction using rooted topological torsion fingerprints in combination with five machine learning (ML) methods: random forest, partial least squares, extreme gradient boosting, lasso regression, and support vector regression. With a large and diverse set of 14 499 experimental pKa values, pKa models were developed for aliphatic amines. The models demonstrated consistently good prediction statistics and were able to generate accurate prospective predictions as validated with an external test set of 726 pKa values (RMSE 0.45, MAE 0.33, and R2 0.84 by the top model). The factors that may affect prediction accuracy and model applicability were carefully assessed. The results demonstrated that rooted topological torsion fingerprints coupled with ML methods provide a promising approach for developing accurate pKa prediction models.

WEST NILE VIRUS MENINGO-ENCEPHALITIS: POSSIBLE SEXUAL TRANSMISSION.

PURPOSE: We report a previously healthy middle aged woman who developed West Nile virus meningo-encephalitis within two weeks of unprotected vaginal intercourse with her husband. SUBJECT: This patient's husband had serologically confirmed West Nile virus infection manifested by a flu-like illness and rash with the sexual contact one day before the onset of his symptoms. RESULT: This well documented neuroinvasive West Nile virus infection in our patient was within the incubation period of transmission and there was no reported mosquito bite exposure. CONCLUSION: The timeframe of infection raises the possibility that her illness was sexually transmitted.

POSIT: Flexible Shape-Guided Docking For Pose Prediction.

We present a new approach to structure-based drug design (POSIT) rigorously built on the simple concept that pose prediction is intimately coupled to the quality and availability of experimental structural data. We demonstrate the feasibility of the approach by performing retrospective analyses on three data sets designed to explore the strengths and weaknesses of POSIT relative to existing methods. We then present results documenting 2.5 years of prospective use of POSIT across a variety of structure-based industrial drug-discovery research projects. We find that POSIT is well-suited to guiding research decision making for structure-based design and, in particular, excels at enabling lead-optimization campaigns. We show that the POSIT framework can drive superior pose-prediction performance and generate results that naturally lend themselves to prospective decision making during lead optimization. We believe the results presented here are (1) the largest prospective validation of a pose prediction method reported to date (71 crystal structures); (2) provide an unprecedented look at the scope of impact of a computational tool; and (3) represent a first-of-its-kind analysis. We hope that this work inspires additional studies that look at the real impact and performance of computational research tools on prospective drug design.

Management of Acute Postoperative Pain in Hand Surgery: A Systematic Review.

PURPOSE: To conduct a systematic review to guide hand surgeons in an evidenced-based approach in managing postoperative pain. METHODS: We performed a literature review for primary research articles on management of postoperative pain in hand surgery patients using Medical Literature Analysis and Retrieval System Online (MEDLINE; PubMed), Excerpta Medica database (EMBASE), and the Cochrane Collaboration Library. Inclusion criteria were primary journal articles examining treatment of acute postoperative pain based on any modality. Data related to pain assessment, postoperative recovery, and total postoperative analgesic consumption were extracted. RESULTS: A total of 903 publications were reviewed; 184 publications underwent abstract review. After applying inclusion and exclusion criteria, 10 primary articles were selected for inclusion in this review. Data were noted to be heterogeneous and findings were compiled. Results were divided into groups evaluating postoperative pain medications or pain infusion catheters. CONCLUSIONS: Although this review did not demonstrate a best practices model for postoperative pain management, it provides evidence for alternative medications and treatment strategies. The evidence available suggests that postoperative pain control should begin before surgery and that combining multiple strategies for pain treatment is beneficial. Given the increasing attention paid to narcotic prescriptions and the potential for abuse, surgeons should adopt evidence-based pain management practices. We provide an example algorithm for pain treatment in hand surgery based on available data and the authors' experience. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic III.

A systematic review of morbidity associated with autologous breast reconstruction before and after exposure to radiotherapy: are current practices ideal?

PURPOSE: The specific aim of this study was to conduct a systematic review of the literature to assess outcomes data on complications and aesthetic results associated with autologous tissue-based breast reconstruction performed before or after chest wall irradiation. METHODS: Studies from a PubMed search that met predetermined inclusion criteria were identified. Complications of interest included partial or total flap loss, fat necrosis, thrombosis, infection, seroma, hematoma, delayed wound healing, and flap fibrosis/contracture. Pooled complication rates were calculated. RESULTS: A total of 20 articles were included in the study for autologous reconstruction. These primary articles were selected after screening 897 publications, with six studies presenting data on pre-reconstruction radiation, nine studies presenting data on post-reconstruction radiation, and five studies presenting data on both patient groups. Comparison of pooled complication rates between flaps irradiated before or after reconstruction were statistically similar, including total flap loss (1 vs. 4 %), wound healing complications (10 vs. 14 %), infection (4 vs. 6 %), hematoma (2 vs. 1 %), seroma (4 vs. 4 %), and fat necrosis (10 vs. 13 %). The pooled rate of flap contracture and fibrosis was 27 % in flap reconstructions exposed to radiotherapy. Statistical evaluation of aesthetic outcomes was impossible as a result of variability in assessment and reporting methods. CONCLUSIONS: Review of the current literature suggests similar rates of complications and success rates in autologous breast reconstruction patients exposed to pre- or post-reconstruction radiation. Immediate autologous reconstruction should be considered as a viable option even in patients who are likely to require postmastectomy radiotherapy.

A systematic review of complications of implant-based breast reconstruction with prereconstruction and postreconstruction radiotherapy.

PURPOSE: To conduct a systematic review of the literature to assess outcomes data on complications associated with implant-based breast reconstruction performed before or after chest wall radiation to assist in guiding the decision-making process for reconstruction of the irradiated breast. METHODS: Studies from a PubMed search that met predetermined inclusion criteria were identified and included. Complications of interest were low- and high-grade capsular contractures, minor and major complications, reconstruction failure rates, and reconstruction completion rates. Pooled complication rates were calculated. RESULTS: A total of 26 articles were included in the study after screening 1,006 publications, with 14 studies presenting data on prereconstruction radiation and 23 studies presenting data on postreconstruction radiation. Complication rates evaluated in patients exposed to radiation before or after implant reconstruction were not significantly different. Reconstruction failure rates were similar at 19 and 20 % for pre- and postreconstruction radiation patients, respectively. Completion rates were similar at 83 and 80 % for pre- and postreconstruction radiation patients, respectively. CONCLUSIONS: Review of the current literature suggests similar overall success and failure rates with radiotherapy provided both before and after reconstruction. Failure rates in both groups of patients are clinically significant when considering implant reconstruction in the setting of radiation.

The application of statistical methods to cognate docking: a path forward?

Cognate docking has been used as a test for pose prediction quality in docking engines for decades. In this paper, we report a statistically rigorous analysis of cognate docking performance using tools in the OpenEye docking suite. We address a number of critically important aspects of the cognate docking problem that are often handled poorly: data set quality, methods of comparison of the predicted pose to the experimental pose, and data analysis. The focus of the paper lies in the third problem, extracting maximally predictive knowledge from comparison data. To this end, we present a multistage protocol for data analysis that by combining classical null-hypothesis significance testing with effect size estimation provides crucial information about quantitative differences in performance between methods as well as the probability of finding such differences in future experiments. We suggest that developers of software and users of software have different levels of interest in different parts of this protocol, with users being primarily interested in effect size estimation while developers may be most interested in statistical significance. This protocol is completely general and therefore will provide the basis for method comparisons of many different kinds.

"Toward Breast Reinnervation- What is our Endpoint" A systematic review of normal breast sensibility.

BACKGROUND: To restore breast sensibility, some centers are offering nerve reconstruction as a component of implant and flap-based breast reconstruction. To interpret and contextualize the results of these procedures, it is necessary to understand the normal range of breast sensibility, the factors that affect it, and the best methods for its objective measurement. METHODS: We conducted systematic and comprehensive searches across PubMed, Web of Science, and Cochrane Library databases using keywords and controlled vocabulary for the concepts of the breast, nipple, areola, and measurement. The search results were imported into Rayyan QCRI for a blinded screening of titles and abstracts. Studies were evaluated for bias using RevMan 5 software. The results of sensory measurements were pooled, and a quantitative summary of breast sensibility was generated. RESULTS: A total of 36 articles were identified, including retrospective, cross-sectional, and prospective studies. Although there were some consistent findings across studies, such that breast sensibility is inversely related to breast volume, there was wide variability in the following parameters: population, breast condition, measurement modality, anatomic areas of measurement, and sensibility findings. This heterogeneity precluded the generation of normative breast sensibility measurements. Furthermore, we detected a high degree of bias in most studies, due to self-selection of participants and failure to record patient characteristics that may alter sensibility. CONCLUSIONS: The literature lacks consistent data delineating normative values for breast sensibility. Standardized measurements of healthy volunteers with various breast characteristics are necessary to elucidate normative values and interpret efforts to restore sensibility in breast reconstruction.

An alternative mucosal flap for nasal lining: the superior labial artery mucosal flap-an anatomic study.

Reconstruction of nasal lining and septal defects is a challenging problem. An ideal reconstructive option provides ample thin, like tissue with reliable perfusion in a relatively short, single-staged procedure. The purpose of this study is to describe the vascular anatomy of the superior labial artery and an axial mucosal flap, the superior labial artery mucosal flap, based on this vascular pedicle, proposed for a single-stage reconstruction of nasal lining and septal defects.Dissection of the 10 facial arteries and their branches with a focus on the superior labial arteries was performed in a total of 5 fresh human cadavers. Objective findings on the vascular anatomy were assessed and upper lip mucosal flaps, medially based on the superior labial artery, were elevated. The case of a 30-year-old man who sustained a dog bite to the nose with a resulting full-thickness loss of his entire nasal tip and partial loss of his alar subunits is presented.In complex cases of nasal reconstruction in which nasal lining of associated defects cannot be accomplished with local flaps, we describe the anatomic basis for a regional single-staged, axial flap alternative for reconstruction.

The treatment of an unusual complication associated with a HeartMate II LVAD in an adolescent.

The HeartMate II LVAD has provided a bridge to heart transplantation or a permanent fixture for destination therapy for patients with heart failure. LVAD infections are associated with significant morbidity even when treated with explantation, device exchange, or a salvage procedure. We present an unusual complication following the placement of the HeartMate II device in an adolescent, whereby a pocket infection resulted in a large soft tissue defect overlying and surrounding the device. The novel use of a VRAM flap was successfully used to repair the defect and salvage the device.

Developing a Mechanistic Approach to Sudden Death Prevention in Mitral Valve Prolapse.

Sudden cardiac death (SCD) from ventricular fibrillation (VF) can occur in mitral valve prolapse (MVP) in the absence of other comorbidities including mitral regurgitation, heart failure or coronary disease. Although only a small proportion with MVP are at risk, it can affect young, otherwise healthy adults, most commonly premenopausal women, often as the first presentation of MVP. In this review, we discuss arrhythmic mechanisms in MVP and mechanistic approaches for sudden death risk assessment and prevention. We define arrhythmogenic or arrhythmic MVP (AMVP) as MVP associated with complex and frequent ventricular ectopy, and malignant MVP (MMVP) as MVP with high risk of SCD. Factors predisposing to AMVP are myxomatous, bileaflet MVP and mitral annular disjunction (MAD). Data from autopsy, cardiac imaging and electrophysiological studies suggest that ectopy in AMVP is due to inflammation, fibrosis and scarring within the left ventricular (LV) base, LV papillary muscles and Purkinje tissue. Postulated mechanisms include repetitive injury to these regions from systolic papillary muscle stretch and abrupt mitral annular dysmotility (excursion and curling) and diastolic endocardial interaction of redundant mitral leaflets and chordae. Whereas AMVP is seen relatively commonly (up to 30%) in those with MVP, MVP-related SCD is rare (2-4%). However, the proportion at risk (i.e., with MMVP) is unknown. The clustering of cardiac morphological and electrophysiological characteristics similar to AMVP in otherwise idiopathic SCD suggests that MMVP arises when specific arrhythmia modulators allow for VF initiation and perpetuation through action potential prolongation, repolarization heterogeneity and Purkinje triggering. Adequately powered prospective studies are needed to assess strategies for identifying MMVP and the primary prevention of SCD, including ICD implantation, sympathetic modulation and early surgical mitral valve repair. Given the low event rate, a collaborative multicenter approach is essential.

Hemodynamic Doppler echocardiographic evaluation of permanent His bundle and biventricular pacing after AV nodal ablation.

placing after atrioventricular (AV) nodal ablation for permanent atrial fibrillation (AF) may include cardiac resynchronization therapy (CRT) with either His bundle pacing (HBP) or biventricular pacing (BVP), or conventional single site right ventricular apical pacing (RVAP). To determine the relationship between pacing method and hemodynamic outcome, we used Doppler echocardiographic methods to evaluate left ventricular (LV) hemodynamics after AV nodal ablation and either HBP, BVP, or RVAP. Method: 20 patients were evaluated > 6 months after AV nodal ablation, 10 each with chronic HBP or BVP, and all with RVAP lead. Doppler echocardiography was used to measure 3 parameters indicative of CRT: 1) LV dP/dt, 2) the LV pre-ejection interval, and 3) myocardial performance index, relative to intra-patient RVAP. Results: Primary endpoint of LV dP/dt on average improved by > 17% with both HBP and BVP, compared to RVAP. HBP but not BVP, had improvement across all three parameters. Conclusion: HBP provides LV electromechanical synchrony across multiple echo Doppler parameters. Both HBP and BVP were hemodynamically superior to RVAP following AV nodal ablation.

Frequency of thrombocytopenia in psoriasis patients treated with tumor necrosis factor-a inhibitors.

Tumor necrosis factor-? (TNF-?) inhibitors are biologic agents that are currently in wide use for the treatment of psoriasis as well as other inflammatory diseases. Following reports of thrombocytopenia as a potential adverse effect of anti-TNF-? therapy, we performed a retrospective study to determine the frequency of thrombocytopenia, defined as a platelet count <50x109 cells/L, in a cohort of 187 psoriatic patients treated with anti-TNF-? agents over a nine-year period. Although none of our patients met serologic criteria for thrombocytopenia or displayed clinical manifestations of thrombocytopenia, two patients developed platelet counts below 100×109 cells/L. Thrombocytopenia induced by anti-TNF-? agents is a potential adverse effect, it is a rare occurrence that will require further investigation in large, placebo-controlled, double-blind, prospective studies.

Packing and postoperative rhinoplasty management: a survey report.

BACKGROUND: Postoperative management following rhinoplasty varies greatly among aesthetic surgeons. Few studies have addressed practice trends in postoperative rhinoplasty care or questioned the frequency of packing and splinting. Many conventional postoperative techniques remain controversial (eg, packing). OBJECTIVE: To investigate current postoperative practices in the United States, correlating the results with surgical education, practice type, and complication rates. METHODS: An online survey was distributed to members of the American Society for Aesthetic Plastic Surgery. Respondents were polled about their background, route of education, type of practice, frequency and preference of postoperative nasal care, and most frequent rhinoplasty complications. Statistical analysis was performed with the χ(2) test. RESULTS: Of the 1550 total surveys sent, 126 responses were received (8.1%). The majority of respondents were in private practice (86%) and trained in plastic surgery (83%). Approximately 33% continue to regularly employ packing following rhinoplasty, but data show that surgeons performing 21 or more rhinoplasties per year were less likely to utilize packing (P = .06). Those surgeons with higher rhinoplasty case volumes were significantly more likely to utilize a secondary therapy (eg, steroids, arnica) in combination with ice packs (P = .03) to prevent postoperative ecchymosis. Finally, surgeons with lower rhinoplasty case volumes reported more frequent postoperative nasal tip deformities (P = .01). CONCLUSIONS: Postoperative rhinoplasty care varies greatly among practicing aesthetic surgeons. Importantly, a high percentage of private practice aesthetic surgeons continue to utilize nasal packing following rhinoplasty. However, these numbers trend downward in surgeons who perform rhinoplasties more frequently.

Heart-Brain Relationship in Stroke.

The patient presenting with stroke often has cardiac-related risk factors which may be involved in the mechanism of the stroke. The diagnostic assessment is predicated on recognition of this potential relationship. Naturally, an accurate history is of utmost importance in discerning a possible cause and effect relationship. The EKG is obviously an important clue as well as it allows immediate assessment for possible cardiac arrhythmia, such as atrial fibrillation, for possible acute ischemic changes reflective of myocardial ischemia, or there may be indirect factors such as the presence of left ventricular hypertrophy, typically seen with longstanding hypertension, which could be indicative of a hypertensive mechanism for a patient presenting with intracerebral hemorrhage. For all presentations in the emergency room, the vital signs are important. An elevated body temperature in a patient presenting with acute stroke raises concern about possible infective endocarditis. An irregular-irregular pulse is an indicator of atrial fibrillation. A markedly elevated blood pressure is not uncommon in both the acute ischemic and acute hemorrhagic stroke setting. One tends to focus on possible cardioembolic stroke if there is the sudden onset of maximum neurological deficit versus the stepwise progression more characteristic of thrombotic stroke. Because of the more sudden loss of vascular supply with embolic occlusion, seizure or syncope at onset tends to be supportive of this mechanism. Different vascular territory involvement on neuroimaging is also a potential indicator of cardioembolic stroke. Identification of a cardiogenic source of embolus in such a setting certainly elevates this mechanism in the differential. There have been major advances in management of acute cerebrovascular disease in recent decades, such as thrombolytic therapy and endovascular thrombectomy, which have somewhat paralleled the advances made in cardiovascular disease. Unfortunately, the successful limitation of myocardial damage in acute coronary syndrome, with intervention, does not necessarily mirror a similar salutary effect on functional outcome with cerebral infarction. The heart can also affect the brain from a cerebral perfusion standpoint. Transient arrhythmias can result in syncope, while cardiac arrest can result in hypoxic-ischemic encephalopathy. Cardiogenic dementia has been identified as a mechanism of cognitive impairment associated with severe cardiac failure. Structural cardiac abnormalities can also play a role in brain insult, and this can include tumors, such as atrial myxoma, patent foramen ovale, with the potential for paradoxical cerebral embolism, and cardiomyopathies, such as Takotsubo, can be associated with precipitous cardioembolic events.

Out-of-Pocket Spending for Thumb Carpometacarpal Arthritis: Capitation Matters.

Background: Patients are increasingly responsible for direct medical expenditures with a growth in out-of-pocket (OOP) expenses, which can impede access to care and affect treatment. This study aims to investigate the impact of capitation on OOP expenses for surgical and presurgical treatment for thumb carpometacarpal (CMC) joint arthritis. Methods: Patients with a diagnosis of thumb CMC arthritis who underwent surgery (2009-2016) comprised our study cohort. Sociodemographic data, total cost, and OOP expenses were collected at the time of surgery and 2 years prior. Patients were stratified by insurance type: fee-for-service (FFS), managed care (MC), Medicare-MC, and Medicare-FFS. Capitated plans were included in the MC and Medicare-MC groups. A generalized linear regression was performed to investigate the association between OOP expenses and insurance type. Results: Our cohort consisted of 7780 patients with FFS insurance, 953 with MC insurance, 2136 with Medicare-FFS, and 265 with Medicare-MC. There was no difference in total costs for FFS and MC (FFS $7281 vs. MC $7306, P = .73; Medicare-FFS $6663 vs. Medicare-MC $6183, P = .19). However, patients with FFS incurred significantly greater OOP costs (FFS $952 vs. MC $434, P < .01; Medicare-FFS $343 vs. Medicare-MC $232, P < .01). In the adjusted regression, MC, Medicare-FFS, and Medicare-MC had approximately 21% to 46% of the predicted OOP expenses of patients with FFS plans (P < .01). Conclusion: Despite similar total costs, OOP expenses were significantly greater for patients with FFS or Medicare-FFS insurance. With healthcare costs transitioning to patients, providers should consider cost sharing when conferring care to help alleviate the financial burden placed on patients.

Combined laparoscopic and microsurgical techniques for testicular autotransplantation: is this still an evolving technique?

Testicular autotransplantation is an advanced technique for the correction of high intra-abdominal testicles with inadequate vascular length for repositioning in the scrotum. In the past, surgeons have often avoided this approach due to the extended operative time and the requirement for microsurgical equipment and training. Surprisingly, this procedure remains rare despite the fact that autotransplantation is sometimes the most viable option to relocate the testicle. Further, current advances in laparoscopic surgery allow for testicular harvesting with minimal morbidity and maximal vascular pedicle length. Here, the evolution and an approach combining these two techniques implemented successfully in five patients are presented.

Ichthyosiform sarcoidosis: A case report and review of the literature.

Sarcoidosis is a potentially life-threatening, multisystem, granulomatous disease that can present with cutaneous manifestations in patients. A rare cutaneous manifestation of this disease may resemble acquired ichthyosis. We report a 45-year-old woman with a several year history of dyspnea on exertion and panuveitis who presented to a county hospital with acquired lower extremity ichthyosis and a biopsy consistent with both acquired ichthyosis and noncaseating, granulomatous sarcoidosis. To our knowledge, this entity has been described in only 22 previous independent cases, with the present case being 1 of only 5 cases to rapidly progress to full systemic involvement. Furthermore, it is important to recognize the manifestations of sarcoidosis in the skin, because these may be the presenting signs of systemic illness.