Connectome reorganization associated with temporal lobe pathology and its surgical resection.

Network neuroscience offers a unique framework to understand the organizational principles of the human brain. Despite recent progress, our understanding of how the brain is modulated by focal lesions remains incomplete. Resection of the temporal lobe is the most effective treatment to control seizures in pharmaco-resistant temporal lobe epilepsy (TLE), making this syndrome a powerful model to study lesional effects on network organization in young and middle-aged adults. Here, we assessed the downstream consequences of a focal lesion and its surgical resection on the brain's structural connectome, and explored how this reorganization relates to clinical variables at the individual patient level. We included adults with pharmaco-resistant TLE (n = 37) who underwent anterior temporal lobectomy between two imaging time points, as well as age- and sex-matched healthy controls who underwent comparable imaging (n = 31). Core to our analysis was the projection of high-dimensional structural connectome data-derived from diffusion MRI tractography from each subject-into lower-dimensional gradients. We then compared connectome gradients in patients relative to controls before surgery, tracked surgically-induced connectome reconfiguration from pre- to postoperative time points, and examined associations to patient-specific clinical and imaging phenotypes. Before surgery, individuals with TLE presented with marked connectome changes in bilateral temporo-parietal regions, reflecting an increased segregation of the ipsilateral anterior temporal lobe from the rest of the brain. Surgery-induced connectome reorganization was localized to this temporo-parietal subnetwork, but primarily involved postoperative integration of contralateral regions with the rest of the brain. Using a partial least-squares analysis, we uncovered a latent clinical imaging signature underlying this pre- to postoperative connectome reorganization, showing that patients who displayed postoperative integration in bilateral fronto-occipital cortices also had greater preoperative ipsilateral hippocampal atrophy, lower seizure frequency and secondarily generalized seizures. Our results bridge the effects of focal brain lesions and their surgical resections with large-scale network reorganization and interindividual clinical variability, thus offering new avenues to examine the fundamental malleability of the human brain.

Cases of Meningococcal Disease Associated with Travel to Saudi Arabia for Umrah Pilgrimage - United States, United Kingdom, and France, 2024.

Invasive meningococcal disease (IMD), caused by infection with the bacterium Neisseria meningitidis, usually manifests as meningitis or septicemia and can be severe and life-threatening (1). Six serogroups (A, B, C, W, X, and Y) account for most cases (2). N. meningitidis is transmitted person-to-person via respiratory droplets and oropharyngeal secretions. Asymptomatic persons can carry N. meningitidis and transmit the bacteria to others, potentially causing illness among susceptible persons. Outbreaks can occur in conjunction with large gatherings (3,4). Vaccines are available to prevent meningococcal disease. Antibiotic prophylaxis for close contacts of infected persons is critical to preventing secondary cases (2).

The SAGES MASTERS program bariatric surgery pathway selects 10 seminal publications on adjustable gastric banding.

BACKGROUND: Bariatric surgery is one of the clinical pathways of the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) Masters Program, and laparoscopic adjustable gastric banding (LAGB) is one of the three anchoring bariatric procedures. To improve surgeon lifelong learning, the Masters Program seeks to identify sentinel articles of each of the 3 bariatric anchoring procedures. In this article, we present the top 10 articles on LAGB. METHODS: A systematic literature search of papers on LAGB was completed, and publications with the most citations and citation index were selected and shared with SAGES Metabolic and Bariatric Surgery Committee members for review. The individual committee members then ranked these papers, and the top 10 papers were chosen based on the composite ranking. RESULTS: The top 10 sentinel publications on LAGB contributed substantially to the body of literature related to the procedure, whether for surgical technique, novel information, or outcome analysis. A summary of each paper including expert appraisal and commentary is presented here. CONCLUSION: These seminal articles have had significant contribution to our understanding and appreciation of the LAGB procedure. Bariatric surgeons should use this resource to enhance their continual education and acquisition of specialized skills.

Delayed Recognition of Coronavirus Disease 2019 (COVID-19) in New York City: A Descriptive Analysis of COVID-19 Illness Prior to 29 February 2020.

BACKGROUND: On 30 January 2020, COVID-19 was declared a Public Health Emergency of International Concern (PHEIC) by the World Health Organization. Almost a month later, on 29 February 2020, the first case in New York City (NYC) was diagnosed. METHODS: Three hundred sixty persons with COVID-19-like illness were reported to the NYC Department of Health and Mental Hygiene (DOHMH) before 29 February, but 37 of these tested negative and 237 were never tested for severe acute respiratory syndrome coronavirus 2. Records of 86 persons with confirmed COVID-19 and reported symptom onset prior to 29 February 2020 were reviewed by 4 physician-epidemiologists. Case-patients were classified as possible delayed recognition (PDR) of COVID-19 when upon medical review the reported onset date was believed to reflect the initial symptoms of COVID-19, or insufficient evidence to classify, when the onset could not be determined with confidence. Clinical and epidemiological factors collected by DOHMH and supplemented with emergency department records were analyzed. RESULTS: Thirty-nine PDR COVID-19 cases were identified. The majority had severe disease with 69% presenting to an emergency department within 2 weeks of symptom onset. The first PDR COVID-19 case had symptom onset on 28 January 2020. Only 7 of the 39 cases (18%) had traveled internationally within 14 days of onset (none to China). CONCLUSIONS: COVID-19 was in NYC before being classified as a PHEIC, and eluded surveillance for another month. The delay in recognition limited mitigation efforts; by the time city- and statewide mandates were enacted, 16 and 22 days later, there was already widespread community transmission.

Serial Interval and Incubation Period Estimates of Monkeypox Virus Infection in 12 Jurisdictions, United States, May-August 2022.

Using data from 12 US health departments, we estimated mean serial interval for monkeypox virus infection to be 8.5 (95% credible interval 7.3-9.9) days for symptom onset, based on 57 case pairs. Mean estimated incubation period was 5.6 (95% credible interval 4.3-7.8) days for symptom onset, based on 35 case pairs.

Enhanced Detection of Charged N-Glycans in the Brain by Infrared Matrix-Assisted Laser Desorption Electrospray Ionization Mass Spectrometric Imaging.

N-linked glycosylation represents a structurally diverse, complex, co- and posttranslational protein modification that bridges metabolism and cellular signaling. Consequently, aberrant protein glycosylation is a hallmark of most pathological scenarios. Due to their complex nature and non-template-driven synthesis, the analysis of glycans is faced with several challenges, underlining the need for new and improved analytical technologies. Spatial profiling of N-glycans through direct imaging on tissue sections reveals the regio-specific and/or disease pathology correlating tissue N-glycans that serve as a disease glycoprint for diagnosis. Infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) is a soft hybrid ionization technique that has been used for diverse mass spectrometry imaging (MSI) applications. Here, we report the first spatial analysis of the brain N-linked glycans by IR-MALDESI MSI, leading to a significant increase in the detection of the brain N-sialoglycans. A formalin-fixed paraffin-embedded mouse brain tissue was analyzed in negative ionization mode after tissue washing, antigen retrieval, and pneumatic application of PNGase F for enzymatic digestion of N-linked glycans. We report a comparative analysis of section thickness on the N-glycan detection using IR-MALDESI. One hundred thirty-six unique N-linked glycans were confidently identified in the brain tissue (with an additional 132 unique N-glycans, not reported in GlyConnect), where more than 50% contained sialic acid residues, which is approximately 3-fold higher than the previous reports. This work demonstrates the first application of IR-MALDESI in N-linked glycan imaging of the brain tissue, leading to a 2.5-fold increase in the in situ total brain N-glycan detection compared to the current gold standard of positive-mode matrix-assisted laser desorption/ionization mass spectrometry imaging. This is also the first report of the application of the MSI toward the identification of sulfoglycans in the rodent brain. Overall, IR-MALDESI-MSI presents a sensitive glycan detection platform to identify tissue-specific and/or disease-specific glycosignature in the brain while preserving the sialoglycans without any chemical derivatization.

Aging Alters the Aortic Proteome in Health and Thoracic Aortic Aneurysm.

BACKGROUND: Aging enhances most chronic diseases but its impact on human aortic tissue in health and in thoracic aortic aneurysms (TAA) remains unclear. METHODS: We employed a human aortic biorepository of healthy specimens (n=17) and those that underwent surgical repair for TAA (n=20). First, we performed proteomics comparing aortas of healthy donors to aneurysmal specimens, in young (ie, <60 years of age) and old (ie, ≥60 years of age) subjects. Second, we measured proteins, via immunoblotting, involved in mitophagy (ie, Parkin) and also mitochondrial-induced inflammatory pathways, specifically TLR (toll-like receptor) 9, STING (stimulator of interferon genes), and IFN (interferon)-ß. RESULTS: Proteomics revealed that aging transformed the aorta both quantitatively and qualitatively from health to TAA. Whereas young aortas exhibited an enrichment of immunologic processes, older aortas exhibited an enrichment of metabolic processes. Immunoblotting revealed that the expression of Parkin directly correlated to subject age in health but inversely to subject age in TAA. In TAA, but not in health, phosphorylation of STING and the expression of IFN-ß was impacted by aging regardless of whether subjects had bicuspid or tricuspid valves. In subjects with bicuspid valves and TAAs, TLR9 expression positively correlated with subject age. Interestingly, whereas phosphorylation of STING was inversely correlated with subject age, IFN-ß positively correlated with subject age. CONCLUSIONS: Aging transforms the human aortic proteome from health to TAA, leading to a differential regulation of biological processes. Our results suggest that the development of therapies to mitigate vascular diseases including TAA may need to be modified depending on subject age.

Preoperative esophageal testing predicts postoperative reflux status in sleeve gastrectomy patients.

BACKGROUND: Patients who undergo vertical sleeve gastrectomy (VSG) are at risk of postoperative GERD. The reasons are multifactorial, but half of conversions to Roux-en Y gastric bypass are for intractable GERD. Our institution routinely performs preoperative pH and high-resolution manometry studies to aid in operative decision making. We hypothesize that abnormal pH studies in concert with ineffective esophageal motility would lead to higher rates of postoperative reflux after VSG. METHODS: A single institution retrospective review was conducted of adult patients who underwent preoperative pH and manometry testing and VSG between 2015 and 2021. Patients filled out a symptom questionnaire at the time of testing. Postoperative reflux was defined by patient-reported symptoms at 1-year follow-up. Univariate logistic regression was used to examine the relationship between esophageal tests and postoperative reflux. The Lui method was used to determine the cutpoint for pH and manometric variables maximizing sensitivity and specificity for postoperative reflux. RESULTS: Of 291 patients who underwent VSG, 66 (22.7%) had a named motility disorder and 67 (23%) had an abnormal DeMeester score. Preoperatively, reflux was reported by 122 patients (41.9%), of those, 69 (56.6%) had resolution. Preoperative pH and manometric abnormalities, and BMI reduction did not predict postoperative reflux status (p = ns). In a subgroup analysis of patients with an abnormal preoperative pH study, the Lui cutpoint to predict postoperative reflux was a DeMeester greater than 24.8. Postoperative reflux symptoms rates above and below this point were 41.9% versus 17.1%, respectively (p = 0.03). CONCLUSION: While manometry abnormalities did not predict postoperative reflux symptoms, GERD burden did. Patients with a mildly elevated DeMeester score had a low risk of postoperative reflux compared to patients with a more abnormal DeMeester score. A preoperative pH study may help guide operative decision-making and lead to better counseling of patients of their risk for reflux after VSG.

CLINICAL AND STRUCTURAL IMPACT OF SUBMACULAR FLUID AFTER PNEUMATIC RETINOPEXY REPAIR FOR RHEGMATOGENOUS RETINAL DETACHMENT.

PURPOSE: To assess the impact of submacular fluid (SMF) after pneumatic retinopexy for primary rhegmatogenous retinal detachment repair. METHODS: Retrospective review of consecutive patients treated with pneumatic retinopexy for primary rhegmatogenous retinal detachment repair. 387 eyes (374 patients) were included, of which 166 underwent optical coherence tomography imaging after successful pneumatic retinopexy. Foveal-centered optical coherence tomography scans were reviewed. RESULTS: SMF occurred in 59 eyes (35.5%) and was associated with macular detachment ( P ≤ 0.001) and phakic lens status ( P = 0.007). Submacular fluid resolved over an average of 9.39 months and was associated with worse preprocedure best-corrected visual acuity and delayed visual recovery. The mean final best-corrected visual acuity was 0.277 logarithm of the minimum angle of resolution (20/40) in eyes with SMF and 0.162 logarithm of the minimum angle of resolution (20/30) in those without SMF ( P < 0.001). Submacular fluid was associated with discontinuity of the interdigitation zone ( P = 0.003), ellipsoid zone ( P = 0.005), and external limiting membrane ( P ≤ 0.001) after SMF resolution. Ellipsoid zone discontinuity was associated with worse visual prognosis ( P = 0.009). CONCLUSION: Trace SMF detected by optical coherence tomography is common after successful pneumatic retinopexy and resulted in delayed visual recovery and increased rates of outer retinal discontinuity after SMF resorption, although the final difference in best-corrected visual acuity in those with and without SMF was minimal.

Role of Aging and the Immune Response to Respiratory Viral Infections: Potential Implications for COVID-19.

Aging impairs immunity to promote diseases, especially respiratory viral infections. The current COVID-19 pandemic, resulting from SARS-CoV-2, induces acute pneumonia, a phenotype that is alarmingly increased with aging. In this article, we review findings of how aging alters immunity to respiratory viral infections to identify age-impacted pathways common to several viral pathogens, permitting us to speculate about potential mechanisms of age-enhanced mortality to COVID-19. Aging generally leads to exaggerated innate immunity, particularly in the form of elevated neutrophil accumulation across murine and large animal studies of influenza infection. COVID-19 patients who succumb exhibit a 2-fold increase in neutrophilia, suggesting that exaggerated innate immunity contributes to age-enhanced mortality to SARS-CoV-2 infection. Further investigation in relevant experimental models will elucidate the mechanisms by which aging impacts respiratory viral infections, including SARS-CoV-2. Such investigation could identify therapies to reduce the suffering of the population at large, but especially among older people, infected with respiratory viruses.

Characteristics and outcomes of patients undergoing paraesophageal hernia repair with selective use of biologic mesh.

BACKGROUND: The use of biologic mesh in paraesophageal hernia repair (PEHR) has been associated with decreased short-term recurrence but no statistically significant difference in long-term recurrence. Because of this, we transitioned from routine to selective use of mesh for PEHR. The aim of this study was to examine our indications for selective mesh use and to evaluate patient outcomes in this population. METHODS: We queried a prospectively maintained database for patients who underwent laparoscopic PEHR with biologic mesh from October 2015 to October 2018, then performed a retrospective chart review. The decision to use mesh was made intraoperatively by the surgeon. Recurrence was defined as the presence of > 2 cm intrathoracic stomach on postoperative upper gastrointestinal (UGI) series. RESULTS: Mesh was used in 61/169 (36%) of first-time PEHRs, and in 47/82 (57%) of redo PEHRs. Among first-time PEHRs, the indications for mesh included hiatal tension (85%), poor crural tissue quality (11%), or both (5%). Radiographic recurrence occurred in 15% of first-time patients (symptomatic N = 2, asymptomatic N = 3). There were no reoperations for recurrence. Among redo PEHRs, the indication for mesh was most commonly the redo nature of the repair itself (55%), but also hiatal tension (51%), poor crural tissue quality (13%), or both (4%). Radiographic recurrence occurred in 21% of patients (symptomatic N = 4, asymptomatic N = 1). There was 1 reoperation for recurrence in the redo-repair group. CONCLUSIONS: We selectively use biologic mesh in a third of our first-time repair patients and in over half of our redo-repair patients when there is a perceived high risk of recurrence based on hiatal tension, poor tissue quality, or prior recurrence. Despite the high risk for radiologic recurrence, there was only 1 reoperation for recurrence in the entire cohort.

Use of post-discharge heparin prophylaxis and the risk of venous thromboembolism and bleeding following bariatric surgery.

INTRODUCTION: Venous thromboembolism (VTE) is a significant cause of morbidity and mortality after bariatric surgery. Roughly 80% of VTEs occur post-discharge. The frequency of post-discharge heparin (PDH) prophylaxis use is unknown, and evidence about benefits and risks is limited. We aimed to determine the rate of use of PDH prophylaxis and evaluate its relationship with VTE and bleeding events. METHODS: Using the Truven Health MarketScan® database, we performed a retrospective cohort study (2007-2015) of adult patients who underwent sleeve gastrectomy or gastric bypass. We determined PDH prophylaxis from outpatient pharmacy claims, and post-discharge 90-day VTE and bleeding events from outpatient and inpatient claims. We used propensity score-adjusted regression models to mitigate confounding bias. RESULTS: Among 43,493 patients (median age 45 years; 78% women; 77% laparoscopic gastric bypass, 17% laparoscopic sleeve gastrectomy, 6% open gastric bypass), 6% received PDH prophylaxis. Overall, 224 patients (0.52%) experienced VTEs, and 806 patients (1.85%) experienced bleeding. The unadjusted VTE rate did not differ between patients who did and did not receive PDH prophylaxis (0.39% vs. 0.52%, respectively; p = 0.347). The unadjusted bleeding rate was higher for the PDH prophylaxis group (2.74% vs. 1.80%, p < 0.001). In our adjusted analysis, a 23% lower risk of VTE in the PDH prophylaxis group was not statistically significant (odds ratio [OR] 0.77, 95% confidence interval [CI] 0.41 to 1.46), whereas the 47% higher risk of bleeding was statistically significant (OR 1.47, 95% CI 1.14 to 1.88). CONCLUSIONS: PDH prophylaxis after bariatric surgery is uncommon. In our analysis, use was not associated with a lower VTE risk but was associated with a higher bleeding risk.

Update: Characteristics of Health Care Personnel with COVID-19 - United States, February 12-July 16, 2020.

As of September 21, 2020, the coronavirus disease 2019 (COVID-19) pandemic had resulted in 6,786,352 cases and 199,024 deaths in the United States.* Health care personnel (HCP) are essential workers at risk for exposure to patients or infectious materials (1). The impact of COVID-19 on U.S. HCP was first described using national case surveillance data in April 2020 (2). Since then, the number of reported HCP with COVID-19 has increased tenfold. This update describes demographic characteristics, underlying medical conditions, hospitalizations, and intensive care unit (ICU) admissions, stratified by vital status, among 100,570 HCP with COVID-19 reported to CDC during February 12-July 16, 2020. HCP occupation type and job setting are newly reported. HCP status was available for 571,708 (22%) of 2,633,585 cases reported to CDC. Most HCP with COVID-19 were female (79%), aged 16-44 years (57%), not hospitalized (92%), and lacked all 10 underlying medical conditions specified on the case report form† (56%). Of HCP with COVID-19, 641 died. Compared with nonfatal COVID-19 HCP cases, a higher percentage of fatal cases occurred in males (38% versus 22%), persons aged ≥65 years (44% versus 4%), non-Hispanic Asians (Asians) (20% versus 9%), non-Hispanic Blacks (Blacks) (32% versus 25%), and persons with any of the 10 underlying medical conditions specified on the case report form (92% versus 41%). From a subset of jurisdictions reporting occupation type or job setting for HCP with COVID-19, nurses were the most frequently identified single occupation type (30%), and nursing and residential care facilities were the most common job setting (67%). Ensuring access to personal protective equipment (PPE) and training, and practices such as universal use of face masks at work, wearing masks in the community, and observing social distancing remain critical strategies to protect HCP and those they serve.

COVID-19 Outbreak - New York City, February 29-June 1, 2020.

New York City (NYC) was an epicenter of the coronavirus disease 2019 (COVID-19) outbreak in the United States during spring 2020 (1). During March-May 2020, approximately 203,000 laboratory-confirmed COVID-19 cases were reported to the NYC Department of Health and Mental Hygiene (DOHMH). To obtain more complete data, DOHMH used supplementary information sources and relied on direct data importation and matching of patient identifiers for data on hospitalization status, the occurrence of death, race/ethnicity, and presence of underlying medical conditions. The highest rates of cases, hospitalizations, and deaths were concentrated in communities of color, high-poverty areas, and among persons aged ≥75 years or with underlying conditions. The crude fatality rate was 9.2% overall and 32.1% among hospitalized patients. Using these data to prevent additional infections among NYC residents during subsequent waves of the pandemic, particularly among those at highest risk for hospitalization and death, is critical. Mitigating COVID-19 transmission among vulnerable groups at high risk for hospitalization and death is an urgent priority. Similar to NYC, other jurisdictions might find the use of supplementary information sources valuable in their efforts to prevent COVID-19 infections.

Success of an EMR-Driven Postpartum Intervention to Improve HPV Vaccination Rates.

Human papillomavirus vaccination (HPV) remains low in the United States. The inpatient postpartum setting provides an innovative opportunity to vaccinate eligible patients. This study evaluated two different interventions to improve HPV vaccination rates in hospitalized postpartum patients: a nurse based protocol and an electronic medical record (EMR) postpartum order prompt. This was a comparative intervention study performed in a prospective cohort of postpartum patients at two affiliated County Hospitals. The intervention was conducted over a 6-month period aimed at increasing HPV vaccination rates through a nurse based protocol at one hospital (H-NBP) and an EMR postpartum order prompt at the second hospital (H-EMR). Outcomes measures included vaccine administration, patient refusal, and vaccine wastage. A multiple logistic regression model was used to compare outcomes. At H-NBP, 143 vaccine-eligible patients (74%) were identified of which 44 (32%) received the HPV vaccine, 66 (46%) refused, and 33 (21%) had missed opportunities. At H-EMR, 169 patients (87%) were identified as vaccine-eligible of which 111 (66%) received the HPV4 vaccine, 24 (14%) refused and 34 (20%) had missed opportunities. After adjusting for sociodemographic variables, patients at H-EMR were nearly 6 times more likely than patients at H-NBP to undergo postpartum HPV vaccination (OR 5.865, CI 3.358-10.245, p value < 0.0001). An EMR prompt offers a greater impact on HPV vaccination rates than a nursing protocol. The feasibility and success of inpatient postpartum HPV vaccination interventions as demonstrated in this study provides insights on how to approach vaccination strategies in nontraditional clinical settings.

The Reliability and Validity of Wearable Inertial Sensors Coupled with the Microsoft Kinect to Measure Shoulder Range-of-Motion.

BACKGROUND: Objective assessment of shoulder joint active range of motion (AROM) is critical to monitor patient progress after conservative or surgical intervention. Advancements in miniature devices have led researchers to validate inertial sensors to capture human movement. This study investigated the construct validity as well as intra- and inter-rater reliability of active shoulder mobility measurements using a coupled system of inertial sensors and the Microsoft Kinect (HumanTrak). METHODS: 50 healthy participants with no history of shoulder pathology were tested bilaterally for fixed and free ROM: (1) shoulder flexion, and (2) abduction using HumanTrak and goniometry. The repeat testing of the standardised protocol was completed after seven days by two physiotherapists. RESULTS: All HumanTrak shoulder movements demonstrated adequate reliability (intra-class correlation (ICC) ≥ 0.70). HumanTrak demonstrated higher intra-rater reliability (ICCs: 0.93 and 0.85) than goniometry (ICCs: 0.75 and 0.53) for measuring free shoulder flexion and abduction AROM, respectively. Similarly, HumanTrak demonstrated higher intra-rater reliability (ICCs: 0.81 and 0.94) than goniometry (ICCs: 0.70 and 0.93) for fixed flexion and abduction AROM, respectively. Construct validity between HumanTrak and goniometry was adequate except for free abduction. The differences between raters were predominately acceptable and below ±10°. CONCLUSIONS: These results indicated that the HumanTrak system is an objective, valid and reliable way to assess and track shoulder ROM.

End-of-life care in an Australian acute hospital: a retrospective observational study.

BACKGROUND: There is a gap in knowledge about the kind and quality of care experienced by hospital patients at the end of their lives. AIMS: To document and compare the patterns in end-of-life care for patients dying across a range of different medical units in an acute care hospital. METHODS: A retrospective observational study of consecutive adult inpatient deaths between 1 July 2010 and 30 June 2014 in four different medical units of an Australian tertiary referral hospital was performed. Units were selected on the basis of highest inpatient death rates and included medical oncology, respiratory medicine, cardiology and gastroenterology/hepatology. RESULTS: Overall, 41% of patients died with active medical treatment plans, but significantly more respiratory and cardiology patients died with ongoing treatment (46 and 75% respectively) than medical oncology and gastroenterology patients (each 27%, P < 0.05). More medical oncology and gastroenterology patients were recognised as dying (92 and 88%) compared with 72% of respiratory and only 38% of cardiology patients (P < 0.001). Significantly, more medical oncology patients were referred to palliative care and received comfort care plans than all other patient groups. However, the rate of non-palliative interventions given in the final 48 h was not significantly different between all four groups. CONCLUSIONS: There were differences in managing the dying process between all disciplines. A possible solution to these discrepancies would be to create an integrated palliative care approach across the hospital. Improving and reducing interdisciplinary practice variations will allow more patients to have a high-quality and safe death in acute hospitals.

Droxidopa for Hypotension of Different Etiologies: Two Case Reports.

Orthostatic hypotension is defined as a decrease in systolic blood pressure of at least 20 mmHg or a decrease in diastolic blood pressure of at least 10 mmHg (or both), within three minutes of moving from a supine to an upright or standing position. Droxidopa is a synthetic amino acid analog that is directly metabolized to norepinephrine by dopa-decarboxylase, subsequently providing alpha and beta-agonist effects to increase blood pressure. It is indicated in the treatment of neurogenic orthostatic hypotension caused by primary autonomic failure that is associated with Parkinson disease, multi-system atrophy, pure autonomic failure, dopamine beta-hydroxylase deficiency, and/or non-diabetic autonomic neuropathy. In addition, it has been studied in other disease states, such as diabetic autonomic neuropathy-associated orthostatic hypotension and supine hypotension. We report on two cases of off-label droxidopa use. The first case was for diabetic autonomic neuropathy-associated orthostatic hypotension, and the second case was for hypotension due to autonomic dysfunction associated with rheumatoid arthritis. Although the outcomes differed in each case, this article contributes to the literature demonstrating that droxidopa may have varying effects in treating orthostatic hypotension of non-neurogenic etiology.

COMBINING EXTERNAL NEEDLE DRAINAGE AND SCLERAL BUCKLING WITH VITRECTOMY FOR THE REPAIR OF BULLOUS RETINAL DETACHMENTS.

PURPOSE: To describe a technique of combined scleral buckle with external needle drainage and vitrectomy in the treatment of bullous exudative retinal detachment, schisis detachment, or bullous retinoschisis threatening the fovea. METHODS: A retrospective chart review of four eyes of four patients who underwent the procedure described. RESULTS: Four eyes of four patients who underwent combined scleral buckling with external needle drainage and vitrectomy by a single surgeon for a bullous exudative retinal detachment, schisis detachment, or bullous retinoschisis threatening the fovea were included in this series. All four patients were attached after a single surgical intervention. No patient developed complications from the external drainage. CONCLUSION: External needle drainage of bullous subretinal or intraschisis fluid in combination with vitrectomy is a successful technique for treating bullous exudative retinal detachments, schisis detachment, or foveal-threatening retinoschisis. The technique avoids many complications associated with conventional drainage procedures. Long-term results seem promising because of extended follow-up demonstrating sustained anatomical success with a single intervention.

Elucidating the molecular basis of PPCD: Effects of decreased ZEB1 expression on corneal endothelial cell function.

PURPOSE: To investigate the functional role that the zinc e-box binding homeobox 1 (ZEB1) gene, which underlies the genetic basis of posterior polymorphous corneal dystrophy 3 (PPCD3), plays in corneal endothelial cell proliferation, apoptosis, migration, and barrier function. METHODS: A human corneal endothelial cell line (HCEnC-21T) was transfected with siRNA targeting ZEB1 mRNA. Cell proliferation, apoptosis, migration, and barrier assays were performed: Cell proliferation was assessed with cell counting using a hemocytometer; cell apoptosis, induced by either ultraviolet C (UVC) radiation or doxorubicin treatment, was quantified by measuring cleaved caspase 3 (cCASP3) protein levels; and cell migration and barrier function were monitored with electric cell-substrate impedance sensing (ECIS). RESULTS: ZEB1 knockdown in HCEnC-21T cells transfected with siRNA targeting ZEB1 did not result in a significant difference in cell proliferation when compared with control. Although knockdown of ZEB1 in HCEnC-21T cells sensitized the cells to UV-induced apoptosis, ZEB1 knockdown did not alter the cells' susceptibility to doxorubicin-induced apoptosis, as measured with cCASP3 protein levels, compared with controls. Similarly, no difference was observed in cell migration following ZEB1 knockdown. However, cell barrier function increased significantly following ZEB1 knockdown. CONCLUSIONS: The corneal endothelium in PPCD3 is characterized by morphologic, anatomic, and molecular features that are more consistent with an epithelial-like rather than an endothelial-like phenotype. Although these characteristics have been well documented, we demonstrate for the first time that susceptibility to UV-induced apoptosis and cell barrier function are significantly altered in the setting of reduced ZEB1. The significance of an altered cellular response to apoptotic stimuli and increased cell barrier function in the pathobiology of PPCD remains to be fully elucidated.