Management Of Complicated Disease Research Articles

Gastrointestinal Dysfunction in Parkinson's Disease: Current and Potential Therapeutics.

Abnormalities in the gastrointestinal (GI) tract of Parkinson’s disease (PD) sufferers were first reported over 200 years ago; however, the extent and role of GI dysfunction in PD disease progression is still unknown. GI dysfunctions, including dysphagia, gastroparesis, and constipation, are amongst the most prevalent non-motor symptoms in PD. These symptoms not only impact patient quality of life, but also complicate disease management. Conventional treatment pathways for GI dysfunctions (i.e., constipation), such as increasing fibre and fluid intake, and the use of over-the-counter laxatives, are generally ineffective in PD patients, and approved compounds such as guanylate cyclase C agonists and selective 5-hyroxytryptamine 4 receptor agonists have demonstrated limited efficacy. Thus, identification of potential targets for novel therapies to alleviate PD-induced GI dysfunctions are essential to improve clinical outcomes and quality of life in people with PD. Unlike the central nervous system (CNS), where PD pathology and the mechanisms involved in CNS damage are relatively well characterised, the effect of PD at the cellular and tissue level in the enteric nervous system (ENS) remains unclear, making it difficult to alleviate or reverse GI symptoms. However, the resurgence of interest in understanding how the GI tract is involved in various disease states, such as PD, has resulted in the identification of novel therapeutic avenues. This review focuses on common PD-related GI symptoms, and summarizes the current treatments available and their limitations. We propose that by targeting the intestinal barrier, ENS, and/or the gut microbiome, may prove successful in alleviating PD-related GI symptoms, and discuss emerging therapies and potential drugs that could be repurposed to target these areas.

The impact of maternal infection with chronic wasting disease on fetal characteristics in wild white-tailed deer (Odocoileus virginianus) in Illinois, USA

Chronic wasting disease (CWD) is a fatal neurodegenerative disease of cervids caused by a misfolded and infectious protein, called a prion. Infection with CWD is characterized by an asymptomatic period, followed by a decline that inevitably leads to death. The disease is transmitted mainly through direct contact between infected and uninfected animals, but vertical transmission has been documented in muntjac deer ( Muntiacus reevesi ), along with the presence of infectious prions in the reproductive tissues of elk ( Cervus canadensis ) and white-tailed deer ( Odocoileus virginianus ). Therefore, questions have been raised about the effects of CWD on the health and characteristics of the offspring gestated by infected animals, and about how vertical transmission may complicate disease management efforts and drive reduction of herd fitness. To begin finding quantitative answers to these questions, this study used multilevel Bayesian linear regression to model the influence of maternal infection with CWD, along with several other environmental and biological variables, on fetal weight, sex, and length using data collected on white-tailed deer as part of the CWD management program in Illinois for the time period between fiscal years 2003 and 2020. The regression analyses found no statistically significant relationship between maternal CWD status and fetal length or the fraction of males in a litter but did find a significant relationship between maternal infection and fetal weight. Fetuses of CWD positive deer weighed 1% less than fetuses from deer in which CWD was not detected. Given that 88% of the fetuses in this data were in the second trimester of gestation, the impact of CWD on fetuses through the entire course of gestation remains to be evaluated. • Fetal weights in the second trimester were 1% lower in CWD positive female deer • Fetal length showed no significant relationship with maternal CWD infection • Fetal sex ratios were 1:1 regardless of maternal CWD infection status

Estudio complementario de la patología biliar complicada y el manejo de la litiasis coledociana en dos tiempos

Background: Nowadays, the prevalence of gallstones ranges between 10 and 20% in Western world, and 7-16% of the patients also present choledocholithiasis. The preoperative diagnosis of choledocholithiasis is difficult. Objective: To establish our experience in the evaluation of complicated gallstone disease and twostage management of choledochal lithiasis as standard or care. Material and methods: This prospective and observational study included patients hospitalized with gallstone disease undergoing procedures in the Department of General Surgery of Hospital Vidal from June 30, 2019, to December 30, 2019. Results: Ultrasound of the liver, biliary tract and pancreas was specific, with accuracy of 80.9% and sensitivity of 50%. Magnetic resonance cholangiopancreatography (MRCP) had a sensitivity of 100%, accuracy of 84.6% and sensitivity of 67%. As for endoscopic retrograde cholangiopancreatography (ERCP), the diagnosis of choledocholithiasis was made in 100% of the cases during the first cholangiography while “control” cholangiography had a sensitivity of 0%, specificity of 100% and accuracy of 15.4%. The presence of a dilated cystic duct intraoperatively in association with abnormal biochemical parameters had a sensitivity of 100%, specificity of 90%, and accuracy of 93.6%. Conclusion: Intraoperative cholangiography (IOC) is the gold standard procedure for the management of complicated gallstone disease. The association of biochemical parameters and a dilated cystic duct has high predictive value for choledochal lithiasis.

Management of complicated biliary disease in the pediatric population

Cholesterol stones and biliary dyskinesia have replaced hemolytic disease as the primary indication for pediatric cholecystectomy. This study looks at the cohort of pediatric patients with complicated biliary disease, defined as choledocholithiasis and/or gallstone pancreatitis, to determine the incidence and best treatment options. A retrospective review of all cholecystectomies performed over 15 years admitted to the surgical service at a single free-standing children's hospital was performed. Patient factors, indications for cholecystectomy, and final treatment were recorded. Complicated gallbladder disease was defined as having image-confirmed choledocholithiasis or gallstone pancreatitis. High-risk patients were those with imaging that demonstrated definitive choledocholithiasis or cholelithiasis with common bile duct enlargement. Low risk patients were those with cholelithiasis or gallbladder sludge on imaging combined with an elevated bilirubin and/or lipase. A total of 695 cholecystectomies were performed over the 15-year time period. Average patient age was 13.4 years. Of the 695 cholecystectomies, 457 were performed for stone disease (66%) (64 hemolytic) and 236 (34.0%) were performed for biliary dyskinesia. Hundred and three (14.8% of all cholecystectomies, 22.5% of those with stone disease) presented with choledocholithiasis and/or gallstone pancreatitis (complicated disease). In high-risk patients, 28/47 (59.6%) underwent endoscopic retrograde cholangiopancreatography/sphincterotomy. In low-risk patients (no choledocholithiasis or common duct enlargement), 13/56 (23.2%) required endoscopic retrograde cholangiopancreatography/sphincterotomy (P < .05). The indication for endoscopic retrograde cholangiopancreatography after cholecystectomy was choledocholithiasis and none of these patients had bile leak complications. The incidence of pediatric complicated biliary disease due to cholesterol stones is equal to that of adults. These data suggest that a patient with imaging evidence of choledocholithiasis or common bile duct enlargement may require endoscopic retrograde cholangiopancreatography, dependent on clinical course, and this should be strongly considered before cholecystectomy. Those without such radiographic findings can undergo laparoscopic cholecystectomy and have postoperative endoscopic retrograde cholangiopancreatography if needed.

Large Evolutionary Rate Heterogeneity among and within HIV-1 Subtypes and CRFs.

HIV-1 is a fast-evolving, genetically diverse virus presently classified into several groups and subtypes. The virus evolves rapidly because of an error-prone polymerase, high rates of recombination, and selection in response to the host immune system and clinical management of the infection. The rate of evolution is also influenced by the rate of virus spread in a population and nature of the outbreak, among other factors. HIV-1 evolution is thus driven by a range of complex genetic, social, and epidemiological factors that complicates disease management and prevention. Here, we quantify the evolutionary (substitution) rate heterogeneity among major HIV-1 subtypes and recombinants by analyzing the largest collection of HIV-1 genetic data spanning the widest possible geographical (100 countries) and temporal (1981–2019) spread. We show that HIV-1 substitution rates vary substantially, sometimes by several folds, both across the virus genome and between major subtypes and recombinants, but also within a subtype. Across subtypes, rates ranged 3.5-fold from 1.34 × 10−3 to 4.72 × 10−3 in env and 2.3-fold from 0.95 × 10−3 to 2.18 × 10−3 substitutions site−1 year−1 in pol. Within the subtype, 3-fold rate variation was observed in env in different human populations. It is possible that HIV-1 lineages in different parts of the world are operating under different selection pressures leading to substantial rate heterogeneity within and between subtypes. We further highlight how such rate heterogeneity can complicate HIV-1 phylodynamic studies, specifically, inferences on epidemiological linkage of transmission clusters based on genetic distance or phylogenetic data, and can mislead estimates about the timing of HIV-1 lineages.

The hop downy mildew pathogen Pseudoperonospora humuli.

Pseudoperonospora humuli is an obligate biotrophic oomycete that causes downy mildew, one of the most devastating diseases of cultivated hop, Humulus lupulus. Downy mildew occurs in all production areas of the crop in the Northern Hemisphere and Argentina. The pathogen overwinters in hop crowns and roots, and causes considerable crop loss. Downy mildew is managed by sanitation practices, planting of resistant cultivars, and fungicide applications. However, the scarcity of sources of host resistance and fungicide resistance in pathogen populations complicates disease management. This review summarizes the current knowledge on the symptoms of the disease, life cycle, virulence factors, and management of hop downy mildew, including various forecasting systems available in the world. Additionally, recent developments in genomics and effector discovery, and the future prospects of using such resources in successful disease management are also discussed.TaxonomyClass: Oomycota; Order: Peronosporales; Family: Peronosporaceae; Genus: Pseudoperonospora; Species: Pseudoperonospora humuli.Disease symptomsThe disease is characterized by systemically infected chlorotic shoots called “spikes". Leaf symptoms and signs include angular chlorotic lesions and profuse sporulation on the abaxial side of the leaf. Under severe disease pressure, dark brown discolouration or lesions are observed on cones. Infected crowns have brown to black streaks when cut open. Cultivars highly susceptible to crown rot may die at this phase of the disease cycle without producing shoots. However, foliar symptoms may not be present on plants with systemically infected root systems.Infection processPathogen mycelium overwinters in buds and crowns, and emerges on infected shoots in spring. Profuse sporulation occurs on infected tissues and sporangia are released and dispersed by air currents. Under favourable conditions, sporangia germinate and produce biflagellate zoospores that infect healthy tissue, thus perpetuating the infection cycle. Though oospores are produced in infected tissues, their role in the infection cycle is not defined.ControlDowny mildew on hop is managed by a combination of sanitation practices and timely fungicide applications. Forecasting systems are used to time fungicide applications for successful management of the disease.Useful Websites https://content.ces.ncsu.edu/hop‐downy‐mildew (North Carolina State University disease factsheet), https://www.canr.msu.edu/resources/michigan‐hop‐management‐guide (Michigan Hop Management Guide), http://uspest.org/risk/models (Oregon State University Integrated Plant Protection Center degree‐day model for hop downy mildew), https://www.usahops.org/cabinet/data/Field‐Guide.pdf (Field Guide for Integrated Pest Management in Hops).

Type IV Laryngeal Cleft: A Therapeutic Challenge

Type IV laryngeal cleft (LC) is a rare congenital malformation often associated with poorer prognosis compared to lower grades LC. The difficulty in managing LC lies in the ventilation prior to cleft repair, intraoperative anesthesia, technical difficulties to repair a longer cleft and higher rates of post-operative complications. We report a case of a premature neonate with type IV LC who underwent early gastrostomy at birth and survived with optimal medical management despite suffering bouts of pneumonia and life-threatening event. After a late cleft repair at 4-month old, she survived for 3 months post-operatively without complication of relapse fistula. Despite our cleft repair, she was unable to be weaned off from ventilator attributed to her poor neurological recovery and subsequently succumbed to death at 7 months. We would like to discuss the management challenges with regards to ventilation, approach of surgery as well as post-operative complication to improve the management of such complicated disease.

Minimally Invasive Management of Diverticular Disease.

Traditionally, management of complicated diverticular disease has involved open damage control operations with large definitive resections and colostomies. Studies are now showing that in a subset of patients who would typically have undergone an open Hartmann's procedure for Hinchey III/IV diverticulitis, a laparoscopic approach is equally safe, and has better outcomes. Similar patients may be good candidates for primary anastomosis to avoid the morbidity and subsequent reversal of a colostomy. While most operations for diverticulitis across the country are still performed open, there has been an incremental shift in practice toward minimally invasive approaches in the elective setting. The most recent data from large trials, most notably the SIGMA trial, found laparoscopic sigmoid colectomy is associated with fewer short-term and long-term complications, decreased pain, improvement in length of stay, and maintains better cost-effectiveness than open resections. Some studies even demonstrate that robotic sigmoid resections can maintain a similar if not more reduction in morbidity as the laparoscopic approach while still remaining cost-effective. Intraoperative approaches also factor into improving outcomes. One of the most feared complications in colorectal surgery is anastomotic leak, and many studies have sought to find ways to minimize this risk. Factors to consider to minimize incidence of leak are the creation of tension-free anastomoses, amount of contamination, adequacy of blood supply, and a patient's use of steroids. Techniques supported by data that decrease anastomotic leaks include preoperative oral antibiotic and mechanical bowel prep, intraoperative splenic flexure mobilization, low-tie ligation of the inferior mesenteric artery, and use of indocyanine green immunofluorescence to assess perfusion. In summary, the management of benign diverticular disease is shifting from open, morbid operations for a very common disease to a minimally invasive approach. In this article, we review those approaches shown to have better outcomes, greater patient satisfaction, and fewer complications.

Patterns of prevalence and contemporary clinical management strategies in complicated acute biliary calculous disease: an ESTES \u2018snapshot audit\u2019 of practice

BackgroundAcute complications of biliary calculi are common, morbid, and complex to manage. Variability exists in the techniques utilized to treat these conditions at an individual surgeon and unit level.AimTo identify, through an international prospective nonrandomized cohort study, the epidemiology and areas of practice variability in management of acute complicated calculous biliary disease (ACCBD) and to correlate them against reported outcomes.MethodsA preplanned analysis of the European Society of Trauma and Emergency Surgery (ESTES) 2018 Complicated Biliary Calculous Disease audit was performed. Patients undergoing emergency hospital admission with ACCBD between 1 October 2018 and 31 October 2018 were included. All eligible patients with acute complicated biliary calculous disease were recorded contemporaneously using a standardized predetermined protocol and a secure online database and followed-up through to 60 days from their admission.EndpointsA two-stage data collection strategy collecting patient demographics, details of operative, endoscopic and radiologic intervention, and outcome metrics. Outcome measures included mortality, surgical morbidity, ICU stay, timing of operative intervention, and length of hospital stay.ResultsThree hundred thirty-eight patients were included, with a mean age of 65 years and 54% were female. Diagnosis at admission were: cholecystitis (45.6%), biliary pancreatitis (21%), choledocholithiasis with and without cholangitis (13.9% and 18%). Index admission cholecystectomy was performed in just 50% of cases, and 28% had an ERCP performed. Morbidity and mortality were low.ConclusionThis first ESTES snapshot audit, a purely descriptive collaborative study, gives rich ‘real world’ insights into local variability in surgical practice as compared to international guidelines, and how this may impact upon outcomes. These granular data will serve to improve overall patient care as well as being hypothesis generating and inform areas needing future prospective study.

Trends in the Surgical Management and Outcomes of Complicated Peptic Ulcer Disease.

Older data indicate that less patients undergo surgery for complicated peptic ulcer disease (PUD). We evaluated contemporary trends in the surgical management and outcomes of patients with complicated PUD. The National Inpatient Sample (2005-2014) was queried for patients with complicated PUD (hemorrhage, perforation, or obstruction). Trend analyses were used to evaluate changes in management and outcomes. There were 1 570 696 admissions for complicated PUD during the study period. Majority (87.0%) presented with hemorrhage, 10.6% presented with perforation, and 2.4% had an obstruction. The average age was 67 years. Overall, admissions with complicated PUD decreased from 180 054 in 2005 to 150 335 in 2014. The proportion of patients managed operatively decreased from 2.5% to 1.9% in the hemorrhage group, 75.0% to 67.4% in the perforation group, and 26.0% to 20.2% in the obstruction group (all P-trend < .05). Overall, among patients managed operatively, the use of acid-reducing procedures decreased from 25.9% to 13.9%, mortality decreased from 11.9% to 9.4% (both P-trend < .001), while complications remained stable (10.4% to 10.3%, P-trend = .830). There are fewer admissions with complicated PUD and more patients are treated nonoperatively. Despite subtle improvements, significant proportions of patients still die from complicated PUD indicating the need for improved preoperative optimization and postoperative care among these patients.

When ESKD complicates disease management: GI bleeding and other GI illnesses.

The presentation of gastrointestinal (GI) illnesses is similar in patients with end-stage kidney disease (ESKD) and in the general population. However, there are several instances where kidney failure and renal replacement therapy (RRT) can affect the course of the disease and its management. In this section, we will focus on unique factors of GI illnesses that should be considered in the ESKD population with and without residual kidney function (RKF). We will also discuss the role of RRT modalities in the occurrence and treatment of GI disease.

Development of NAMASTE (New Anxiety Management Algorithm Standardizing Treatment Experience) and Implementation in Primary Care.

Evidence-based depression treatment in primary care is well established. However, clinicians are less likely to be trained to diagnose and treat anxiety disorder, which is frequently comorbid, poses an independent risk for suicidality, and complicates disease management. The University of North Carolina's Internal Medicine Clinic developed a measurement-guided approach to identifying and treating anxiety disorder using the seven-item Generalized Anxiety Disorder Scale, treatment algorithms, medication charts, case-based training for best practices, onsite behavioral counseling, and psychiatric consultation. NAMASTE (new anxiety management algorithm standardizing treatment experience) offers a treatment approach for primary care and addresses a major unmet need in public health and medical education.

A CASE STUDY ON CLINICAL PHARMACIST INTERVENTIONS IN THE MANAGEMENT OF DIABETES COMPLICATED CORONARY ARTERY DISEASE IN HEALTH-CARE PRACTICE

Objective: The objective of the study was to assess the clinical pharmacist interventions in the management of diabetes complicated coronary artery disease.&#x0D; Methods: In the present study, a case history of a 55-year-old female was suffering from diabetes with coronary artery disease was taken. The case was collected from the cardiology outpatient department in a tertiary care hospital. The case was analyzed from 1 to 3 months. The initial visit to the end of final visit her laboratory parameters was examined at the laboratory.&#x0D; Results: The test report of electrocardiogram revealed sinus rhythm. The patient was advised for an echocardiogram which confirmed coronary artery disease. The patient was subjected to a coronary angiogram, which revealed the presence of double-vessel disease. Her ankle-brachial index study test revealed peripheral artery disease. The patient was diagnosed with coronary artery disease, and she was prescribed with regular medications. The patient was monitored for 1-week duration and prescribed with coronary artery disease medications to normalize the condition. The patient was improved with the treatment and advised for regular follow-ups.&#x0D; Conclusion: The study concludes that there was an imperative need for regular health screening by the physician associated clinical pharmacist care services with an effective treatment modality that can reduce the coronary artery disease incidences in this patient.

Perioperative management of pyoderma gangrenosum

Pyodermagangrenosum (PG) classically presents with an acute inflammatory stage, characterized by rapid evolution of painful ulcerations. The pathergy associated with PG lesions complicates disease management. Although PG is commonly treated with immunosuppression, some patients have refractory noninflammatory ulcers. In this subpopulation, there are case reports of successful surgical treatment. However, there is no consensus on optimal perioperative treatment for patients with PG undergoing surgery of any kind, PG related or otherwise. Therefore, we conducted a comprehensive literature review describing perioperative management practices and risk factors that may predict response to surgical intervention. We identified 126 cases of surgical intervention in patients with active PG; among these, only 16.7% experienced postoperative disease progression. No perioperative treatments or clinical risk factors were identified as statistically significant predictors of disease recurrence. Although limited by case series design and publication bias, this study is a valuable means of hypothesis generation for this rare condition.

The impact of comorbidities on severe asthma.

Severe asthma is often associated with numerous comorbidities that complicate disease management and affect patient's outcomes. They contribute to poor disease control and mimic asthma symptoms. Although some comorbidities such as obstructive sleep apnea, bronchiectasis, and chronic obstructive pulmonary disease are generally well recognized, many other may remain undiagnosed but may be detected in an expert specialist setting. The management of comorbidities seems to improve asthma outcomes, and optimizes therapy by avoiding overtreatment. The present review provides recent knowledge regarding the most common comorbidities which are associated with severe asthma. Comorbidities are more prevalent in severe asthma than in mild-to-moderate disease or in the general population. They can be grouped into two large domains: the pulmonary domain and the extrapulmonary domain. Pulmonary comorbidities include upper respiratory tract disorders (obstructive sleep apnea, allergic and nonallergic rhinitis, chronic rhinosinusitis, nasal polyposis) and middle/lower respiratory tract disorders (chronic obstructive pulmonary disease, allergic bronchopulmonary aspergillosis and fungal sensitization, bronchiectasis, dysfunctional breathing). Extrapulmonary comorbidities include anxiety, depression, gastro-esophageal reflux disease, obesity, cardiovascular, and metabolic diseases. The identification of comorbidities via multidimensional approach is needed to initiate appropriate multidisciplinary management of patients with severe asthma.

Delineating Genotype × Environment interactions towards durable resistance in mungbean against Cercospora leaf spot (Cercospora canescens) using GGE biplot

AbstractCercospora leaf spot (Cercospora canescens) is a major fungal disease which impedes mungbean production worldwide. Presence of wider host range with existence of pathogenic variability creates intricacy towards host‐pathogen dynamics. Moreover, environmental factors having crucial role in augmenting severity of this disease further complicate disease management. An attempt has been made for unfolding genotype x environment interactions towards identifying and validating durable resistant genotypes against cercospora leaf spot in multi‐environment testing. Preliminary screening with 246 genotypes under artificial epiphytotic condition was conducted to extract out a subset of 22 mungbean genotypes for further evaluation in field testing across six environments consecutively for two years. GGE biplot analysis detected significant environmental influence towards genotypic response and confirmed the presence of non‐crossover interaction with incoherent genotypic response, thus advocating the urgency for multi‐location testing. GGE biplot aptly identified “LGG 460” and “COGG 912” as “ideal” and “desirable” genotypes, respectively having durable resistance and genetic homeostasis and thus suggested for their utilization in future resistance breeding programme in mungbean against cercospora leaf spot.

Small-bowel capsule endoscopy in patients with celiac disease, axial versus lateral/panoramic view: Results from a prospective randomized trial.

Capsule enteroscopy (CE) is recommended in the management of complicated celiac disease (CD). However, published data are derived from axial-view capsule systems. No data are available on the use of lateral/panoramic view capsules. This study aimed at evaluating the diagnostic yield and efficacy of the lateral/panoramic versus the axial view capsule system in CD. Consecutive CD patients were enrolled in a prospective monocentric study. Each patient ingested an axial (PillCam SB3) and a lateral/panoramic (CapsoCam Plus) view capsule with a 3-h interval in a randomized order. Two experts blindly evaluated the CE carried out. A third expert reviewed the videos in cases of discordance. Twenty-five CD patients were enrolled (four males, age at CE 51.2±16.6years, age at CD diagnosis 41.7±20.6,years on a gluten-free diet [GFD] 9.6±9.4). Indications at CE were refractory CD in nine cases, non-responsiveness to GFD in 10 and GFD non-compliance in six. A positive finding was evidenced in 15 (60%) and 13 (52%) cases by CapsoCam and PillCam respectively (not significant). Atrophy was detected by both capsules. Considering the percentage of the small-bowel mucosa presenting atrophy signs, mean values were 22%±35 and 20%±29 for lateral/panoramic and axial systems, respectively (not significant). Compared to duodenal histology, PillCam correctly identified 80% of patients with SB atrophy, whereas CapsoCam identified 73% of cases. Lateral/panoramic view CE is effective in the detection of small-bowel atrophy in CD and presents good sensitivity and specificity when compared to histology.

Perioperative laboratory monitoring in congenital haemophilia patients with inhibitors: a systematic literature review.

: Although the use of clotting factor concentrates is the mainstay of haemophilia care, the development of inhibitors complicates disease management. Perioperative management of patients with inhibitors is therefore a challenge. A systematic literature review was performed to identify literature reporting on the perioperative monitoring and management of haemophilia. MEDLINE, Embase and Cochrane databases were searched from database inception to 26 March 2018. Recent congress proceedings were also searched. Titles and abstracts, then full texts, were screened for relevance by two reviewers. Quality of included studies was assessed using the Critical Appraisal Skills Programme checklist. Of the 2033 individual entries identified, 86 articles met the inclusion criteria. The identified studies were screened again to find articles reporting perioperative laboratory monitoring in patients with congenital haemophilia A or B, resulting in 24 articles undergoing data extraction. Routine perioperative assay monitoring practices were the most commonly reported (n = 20/24); thrombin generation assay was the least commonly reported (n = 2/24). Other monitoring practices described were factor VII and factor VIII coagulation activity (n = 8/24, n = 5/24, respectively), and thromboelastography or rotational thromboelastometry assessments (n = 3/24). The impact of monitoring on treatment decisions was, however, rarely reported. In conclusion, many methods of perioperative monitoring of haemophilia patients with inhibitors have been identified in this review, yet there is a lack of reporting in larger scale cohort studies. More detailed reporting on the impact of monitoring outcomes on treatment decisions is also needed to share best practice, particularly as new therapeutic agents emerge.

Management of Complicated Gallstone Disease

Nearly 9% of men and 30% of women in the United States experience symptoms or complications of gallstone disease. As such, nearly every general surgeon in the country encounters patients with this pathology numerous times during his or her career. Cholelithiasis can cause complications such as acute cholecystitis, choledocholithiasis, gallstone pancreatitis, and the rare entities of Mirizzi syndrome and gallstone ileus. Patients with gallstones have a 1 to 3% risk per year of a complication, and that risk increases significantly to 30% in those with biliary colic. Surgical management of the complications of gallstones is especially intriguing because the cases are often perceived as low complexity; however, it is an operation that can challenge even the most seasoned attending and result in significant complications. Studies demonstrate complication rates up to 10% following cholecystectomy, with bile duct injury rates hovering at 4 in 1,000. This chapter aims to provide the reader with knowledge of the presentation, imaging, work-up, and framework for the management of complicate gallbladder disease. Furthermore, we hope to provide you with a foundation of how to perform a safe cholecystectomy in a variety of circumstances and impart a few tips and tricks for some challenging intraoperative situations. This review contains 2 figures, and 55 references. Key Words: cholecystitis, choledocholithiasis, cholescintigraphy, common bile duct exploration, critical view of safety, ERCP, gallstone pancreatitis, subtotal cholecystectomy

Epidemiology and treatment of multiple sclerosis in elderly populations.

The prevalence of multiple sclerosis (MS) and the age of affected patients are increasing owing to increased longevity of the general population and the availability of effective disease-modifying therapies. However, ageing presents unique challenges in patients with MS largely as a result of their increased frequency of age-related and MS-related comorbidities as well as transition of the disease course from an inflammatory to a neurodegenerative phenotype. Immunosenescence (the weakening of the immune system associated with natural ageing) might be at least partly responsible for this transition, which further complicates disease management. Currently approved therapies for MS are effective in preventing relapse but are not as effective in preventing the accumulation of disability associated with ageing and disease progression. Thus, ageing patients with MS represent a uniquely challenging population that is currently underserved by existing therapeutic regimens. This Review focuses on the epidemiology of MS in ageing patients. Unique considerations relevant to this population are discussed, including the immunology and pathobiology of the complex relationship between ageing and MS, the safety and efficacy of disease-modifying therapies, when discontinuation of treatment might be appropriate and the important role of approaches to support wellness and cognition.