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Background: Oropharyngeal squamous cell carcinoma (OPSCC) positive for human papillomavirus (HPV) increases wolrd wide. Aims/objectives: The objective for this study has been to evaluate tumor phenotypes and tumor host responses with respect to five-year disease-specific survival (DSS) in HPV(+) and HPV(−) patients. Material and methods: Two hundred patients with OPSCC have been treated between 1992 and 2010. Histopathology slides from these patients have been morphologically evaluated in formalin-fixed, paraffin-embedded (FFPE) stained with hematoxylin-eosin (HE). From HE-stained sections tumor phenotype (keratinization, fraction of mature cancer cells and pattern of invasion) and tumor host responses (inflammation and stromal desmoplasia) were evaluated with respect to five years DSS. Results: High tumor inflammatory response and low stromal desmoplasia had an independent effect predicting better five-year DSS among all patients and when analyzed separately in the HPV(−) and HPV(+) cohort of patients using a Cox regression survival analysis that also included standard clinical prognostic variables among OPSCC patients. Conclusion: Tumor host responses, inflammation and stromal desmoplasia may become part of routine work-up in OPSCC patients due to prognostic value. Significance: We present a method, accessible in most clinical locations and would give important additional information about prognosis in OPSCC patients. [ABSTRACT FROM AUTHOR]

Lateral abdominal wall defects, while rare, present a more challenging problem than commonly encountered ventral defects due to the complexity of the anatomy, physiologic forces, and impact of muscle denervation. The lateral abdominal wall encompasses a large surface area ranging from the costal margin superiorly to the iliac crest inferiorly and from the linea semilunaris anteriorly to the paraspinous musculature posteriorly. The ratio of muscle to fascia/aponeurosis is much higher, which makes repair through muscle tissue versus fascia less secure. Furthermore, these defects are subject to asymmetric forces caused by the independent contraction of anterior and posterior muscle units, which lead to unbalanced strain and hernia progression. These features necessitate the use of wide underlay mesh load bearing repairs supported by the static pillars of the abdominal wall. Management can be further complicated when defects extend beyond the defined boundaries, requiring surgical repair to be adapted based on the border structures involved. Primary fascial coaptation may not be as easily accomplished, and therefore careful planning is important to ensure stable coverage of exposed mesh. [ABSTRACT FROM AUTHOR]

Background Although widely used in maternity care, the risks associated with local anaesthetic (LA) agents are commonly overlooked. The most serious avoidable risk associated with LA use is local anaesthetic systemic toxicity (LAST). Incidence in maternity settings is known to be underestimated due to under-recognition and under-reporting. LAST is a considerable problem, with potential financial and medico-legal as well as implications for patient safety. Methods A standardised, anonymised questionnaire was used to evaluate LAST awareness among staff of all disciplines. Awareness was examined across four domains: LA safe maximum doses, signs and symptoms of toxicity, immediate management, and the antidote type and location. Findings Poor LAST awareness was identified across all staff disciplines, with scope for substantial improvement with an interprofessional educational intervention. Only 17% were aware of any guidelines relating to LAST. Conclusion There is a need for greater focus on interdisciplinary education and the importance of shared responsibility in optimising patient safety. [ABSTRACT FROM AUTHOR]

Background and Aims: Caudal analgesia is a good, reliable, and easy method to provide intraoperative and postoperative analgesia for infra-umbilical surgeries in children. Many additives are being used in combination with local anesthetics in caudal block to prolong the postoperative analgesia (clonidine, midazolam, ketamine, fentanyl, and dexmedetomidine). The purpose of this study was to compare the intraoperative hemodynamics, postoperative analgesia, postoperative rescue analgesic requirement, postoperative sedation and side-effects of clonidine and midazolam used as adjuvants to bupivacaine for caudal analgesia. Material and Methods: Following approval from Institutional Ethical Research Committee, 75 American Society of Anesthesiologists I and II patients aged between 1 and 7 years undergoing various elective infra-umbilical surgical procedures were included in this study. The patients were randomly allocated into three groups of 25 patients each. Group B received 1 ml/kg 0.25% bupivacaine in normal saline, Group BC received 1 ml/kg 0.25% bupivacaine + 1 µg/kg clonidine in normal saline, and Group BM received 1ml/kg 0.25% bupivacaine + 30 µg/kg midazolam in normal saline. The various parameters studied were intraoperative hemodynamic changes, duration of postoperative analgesia, postoperative sedation, postoperative analgesic requirement, and incidence of side-effects. Results: All the groups were similar with respect to patient and block characteristics. The hemodynamic parameters before and after administering caudal analgesia were also comparable. The mean duration of analgesia was 724.80 ± 60.29 min in Group BC, 605.40 ± 82.37 min in Group BM and 295.00 ± 41.78 min in Group B. Thus, the duration of analgesia was significantly prolonged in Group BC compared to Groups BM and B. The FLACC pain score was higher in Group B at the end of 4th, 8th and 12th h compared with Group BC and Group BM. Furthermore at the end of 12th h, pain scores were significantly higher in Group BM compared to Group BC. Only 1 child in Group BC received three rescue medications compared to 15 (60%) children in Group B and 7 (28%) children in Group BM. None of the groups were treated for bradycardia or hypotension and no significant sedation was noted. Conclusion: This study showed that the addition of both clonidine (1 µg/kg) and midazolam (30 µg/kg) with bupivacaine administered caudally significantly increase the duration of postoperative analgesia with minimal side-effects in children. The use of clonidine as an additive to bupivacaine in caudal epidural is a superior choice to midazolam as it reduces the demand of postoperative rescue analgesics significantly. [ABSTRACT FROM AUTHOR]

Background: Due to increase in road traffic and sports injuries, tears of anterior cruciate ligament (ACL) and the posterior cruciate ligament (PCL) of the knee are common. Magnetic resonance imaging (MRI) is emerging as an important tool of diagnosis and evaluation of these injuries. Methods: We carried out a prospective study on role of MRI on ten patients who had undergone ACL or PCL repair over a period of six months. In this report we present three illustrative cases to capture the spectrum of findings in our series to underline the role of MRI in management of such injuries and discuss the modalities of the procedure. Results: In our series, as demonstrated by the cases, MRI had an important role in diagnosis and evaluation of injuries to the cruciate ligaments. Conclusion: MRI can play an important role, particularly in tertiary centres, in diagnosis and evaluation of reconstructed ACL and PCL ligaments of the knee joint. [ABSTRACT FROM AUTHOR]

Background: To evaluate results of a technique for treating neglected epiphyseal injuries of the distal radius with ulnar impaction.Materials and Methods: This retrospective study involved six cases (four males; two females), all of whom sustained the primary injury during childhood (range 9-12 years of age). All presented with wrist deformity and ulnar-sided wrist pain. They were managed with osteotomy of the distal radius, osteotomy and shortening of the ulna, harvesting the bone grafts, and distal radioulnar joint (DRUJ) reduction performed simultaneously through a dorsal midline approach. Mean follow-up was 30 months (range 24-36).Results: Deformity correction and pain relief was observed in all patients. Flexion arc increased from an average of 60° to 102.5°, supination from an average of 31.67° to 67.50°, and pronation from an average of 30.83° to 61.67°. The mean preoperative DASH score was 87.5, which improved to 18.72 postoperatively.Conclusion: Neglected epiphyseal injuries of the distal radius are difficult to manage and many variations are described for handing each of the associated problems. Our technique provides an option for managing this injury with an easy surgical approach, single incision, and cost effectiveness. All the four components of the surgery, which include osteotomy of the distal radius, osteotomy of the ulna, harvesting the bone grafts, and DRUJ reduction were done through a single incision and in a single sitting. Level of evidence IV. [ABSTRACT FROM AUTHOR]

Currently, 5.4 million Americans suffer from AD, and these numbers are expected to increase up to 16 million by 2050. Despite tremendous research efforts, we still do not have drugs or agents that can delay, or prevent AD and its progression, and we still do not have early detectable biomarkers for AD. Multiple cellular changes have been implicated in AD, including synaptic damage, mitochondrial damage, production and accumulation of Aβ and phosphorylated tau, inflammatory response, deficits in neurotransmitters, deregulation of the cell cycle, and hormonal imbalance. Research into AD has revealed that miRNAs are involved in each of these cellular changes and interfere with gene regulation and translation. Recent discoveries in molecular biology have also revealed that microRNAs play a major role in post-translational regulation of gene expression. The purpose of this article is to review research that has assessed neuroprotective and neurodegenerative characteristics of microRNAs in brain samples from AD transgenic mouse models and patients with AD. [ABSTRACT FROM AUTHOR]

Introduction: Intertrochanteric fractures are common in elderly population and pose a significant financial burden to the society. Anatomically contoured proximal femur locking compression plate (PFLCP) is the latest addition in the surgeons' armamentarium to deal with these fractures. It creates an angular stable construct, which will theoretically lessen the risk of failure by screw cut-out and varus collapse, the common mode of DHS failure. We compared DHS with PFLCP in AO type 31A1 and 31A2 intertrochanteric fractures. Materials and Methods: A randomized prospective study was carried out between June 2011 and June 2013. 26 cases each of DHS and PFLCP were included. Results: Functional and radiological outcome was similar in both groups. Conclusion: Both DHS and PFLCP are good choices for stable intertrochanteric fractures, and both lead to excellent functional outcomes, but non-union might be more common with PFLCP. [ABSTRACT FROM AUTHOR]

Purpose: To compare two commonly used methods of temporary hemiepiphysiodesis (staples and figure of eight plate) in the management of coronal plane deformities of the knee in skeletally immature children. Methods: This prospective study was conducted between November 2012 and November 2015. A total of 40 patients with 67 affected knee joints, having at least 1 year of skeletal growth remaining, were included in the study. Angular correction was measured by recording the mechanical lateral distal femoral angle (mLDFA), mechanical medial proximal tibial angle (mMPTA), and anatomical tibio-femoral angle (TFA) (for the overall alignment of lower limbs). Implant removal was done after 5° of overcorrection was achieved. The rate of correction (° per month) and complications related to each technique were recorded. Results: The most common diagnosis was idiopathic genu valgum. The overall rate of correction (TFA) was 1.2° for staples and 1.4° for eight plate ( p = 0.70, not statistically significant). The correction in mLDFA was statistically better in the eight plate group, whereas an opposite trend was recorded in mMPTA. Implant-related complications were present in two cases of the staples group. Conclusion: Although the overall correction rate was similar in both groups, implant-related complications were lower with figure of eight plate. In idiopathic genu valgum (the most common diagnosis), the correction was statistically better in the eight plate group. We recommend figure of eight plate over staples in managing these deformities. [ABSTRACT FROM AUTHOR]

Tumefactive demyelinating (TD) lesions are extremely challenging lesions to diagnose during their histopathological examination and are often misdiagnosed as tumors. On the contrary, a glioblastoma multiforme is rarely misdiagnosed as a TD unless the two coexist. We present a case of a 60-year old man who was diagnosed as having tumefactive demyelination on a stereotactic biopsy. At autopsy, however, the lesion revealed a grade IV glioblastoma. The myelin loss along the periphery of the lesion was erroneously interpreted as TD during the histopathological examination. We have described the imaging, the biopsy, and the autopsy findings of this instructive case. It is pertinent to recognize its histology to prevent a misdiagnosis. [ABSTRACT FROM AUTHOR]

Purpose: Crude coal tar and its derivatives have been used in modern medicine for the treatment of psoriasis since at least 1925 as part of the Goeckerman regimen. To this day, coal tar remains a safe and highly effective option for the treatment of psoriasis vulgaris. However, the mechanism by which coal tar has its therapeutic effect is unknown. This review summarizes current knowledge of the mechanism by which coal tar has its therapeutic effect in the treatment of psoriasis vulgaris. Material and methods: A Pubmed search was conducted on March 13, 2017 for relevant English language journal articles on the subject and were relevant journal articles were included in this review. Results: Crude coal tar consists of thousands of ingredients, many of which are unidentified. Of these ingredients, the most research has gone into analyzing polycyclic aryl hydrocarbons. These hydrocarbons are thought to be the most likely component of crude coal tar that leads to its effects in psoriasis. Of the aryl hydrocarbons, carbazole has been the most well studied in psoriasis and is hypothesized as being responsible for the treatment efficacy of crude coal tar. Conclusions: Polycyclic aryl hydrocarbons, and specifically carbazole, are thought to be the mechanism by which crude coal tar has its effect in psoriasis. However, further research is warranted to fully characterize the mechanism of action of crude coal tar, with the potential to create new therapies for psoriasis. [ABSTRACT FROM AUTHOR]

A 30-year-old male with bilateral acute visual loss presented with retinal edema in the posterior pole and peripapillary region with extensive retinal hemorrhages. Fluorescein angiography revealed delayed arterial filling in the right eye and absent arterial filling in the left eye, suggesting bilateral central retinal artery occlusion. Systemic evaluation revealed a history of chronic low-grade fever and generalized lymphadenopathy. HIV (ELISA) was positive, and other systemic comorbidities were ruled out. Cervical lymph node biopsy stained positive for acid-fast bacilli, with large areas of necrosis, palisaded by epithelioid cell granulomas, macrophages, and multinucleated giant cells, suggesting lymph node tuberculosis. Despite antiretroviral and antitubercular therapy, he developed optic atrophy at 4 weeks. [ABSTRACT FROM AUTHOR]

Background-Regional variation in the incidence and outcomes of in-hospital cardiac arrest (IHCA) is not well studied and may have important health and policy implications. Methods and Results-We used the 2003 to 2011 Nationwide Inpatient Sample databases to identify patients ⩾18 years of age who underwent cardiopulmonary resuscitation (International Classification of Diseases, Ninth Edition, Clinical Modification procedure codes 99.60 and 99.63) for IHCA. Regional differences in IHCA incidence, survival to hospital discharge, and resource use (total hospital cost and discharge disposition among survivors) were analyzed. Of 838 465 patients with IHCA, 162 270 (19.4%) were in the Northeast, 159 581 (19.0%) were in the Midwest, 316 201 (37.7%) were in the South, and 200 413 (23.9%) were in the West. Overall IHCA incidence in the United States was 2.85 per 1000 hospital admissions. IHCA incidence was lowest in the Midwest and highest in the West (2.33 and 3.73 per 1000 hospital admissions, respectively). Compared with the Northeast, risk-adjusted survival to discharge was significantly higher in the Midwest (odds ratio, 1.33; 95% confidence interval, 1.31-1.36), South (odds ratio, 1.21; 95% confidence interval, 1.19-1.23), and West (odds ratio, 1.25; 95% confidence interval, 1.23-1.27). IHCA survival increased significantly from 2003 to 2011 in the United States and in all regions (all Ptrend<0.001). Total hospital cost was highest in the West, whereas discharge to skilled nursing facility and use of home health care among survivors was highest in the Northeast. Conclusions-We observed significant regional variation in IHCA incidence, survival, and resource use in the United States. This variation was explained only partially by differences in patient and hospital characteristics. Further studies are needed to identify other potential factors responsible for these regional differences to improve outcomes after IHCA. [ABSTRACT FROM AUTHOR]

The current American Heart Association/American College of Cardiology guidelines for patients with stable angina pectoris recommend β-blockers as the initial drug therapy for prevention of angina pectoris (class I B indication). Long-acting nitrates or calcium channel blockers should be prescribed for prevention of angina when β-blockers are contraindicated or not tolerated secondary to side effects (class I B indication). Long-acting nitrates or calcium channel blockers in combination with β-blockers should be prescribed for angina prevention when initial treatment with β-blockers is unsuccessful (class I B indication). Only sublingual nitroglycerin or nitroglycerin spray should be used for immediate relief of angina pectoris (class I B indication). Ranolazine with β-blockers can be used for prevention of angina when initial treatment with β-blockers is not successful (class IIa A indication). If angina persists despite treatment with β-blockers, long-acting nitrates and calcium channel blockers, we recommend the addition of ranolazine for prevention of stable angina pectoris. This editorial discusses the contemporary role of ranolazine in the management of patients with stable angina pectoris. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Flavonoids and polyphenols are heterocyclic molecules that have been associated with beneficial effects on human health, such as reducing the risk of various diseases like cancer, diabetes, and cardiovascular and brain diseases. Protocatechuic acid (PCA) is a type of widely distributed naturally occurring phenolic acid. PCA has structural similarity with gallic acid, caffeic acid, vanillic acid, and syringic acid which are well-known antioxidant compounds. More than 500 plants contain PCA as active constituents imparting various pharmacological activity and these effects are due to their antioxidant activities, along with other possible mechanisms, such as anti-inflammatory properties and interaction with several enzymes. Over the past two decades, there have been an increasing number of publications on polyphenols and flavonoids, which demonstrate the importance of understanding the chemistry behind the antioxidant activities of both natural and synthesized compounds, considering the benefits from their dietary ingestion as well as pharmacological use. This work aims to review the pharmacological effects of PCA molecules in humans and the structural aspects that contribute to these effects. [ABSTRACT FROM AUTHOR]

Objective: To investigate recent trends in surgical volume and associated patient outcomes in the treatment of acoustic neuromas. Methods: A retrospective analysis was performed using the Nationwide Inpatient Sample database from 2000–2007; cases from 2005 were excluded because of coding inconsistencies. Univariate and multivariate analyses were used to describe surgical trends and analyze inpatient outcomes. Results: Among 14,928 patients studied, 87.1% were treated at large (based on number of beds) hospitals. Cases at these hospitals declined progressively from 2054 to 1467 cases (a 28.6% decrease) from 2000–2007; a 40.8% (178 cases per year, R 2 = 0.73) reduction in surgeries was observed from 2001–2007. Although mortality remained steady at 0.3%, nonroutine discharge (increase from 10.9% to 19.1%) and complication rates (increase from 21.5% to 23.3%) increased in recent years. Patients without private insurance had an increased risk of nonroutine discharge (odds ratio [OR] 1.7, P = 0.0033; OR 1.5, P = 0.0382), and patients with more comorbidities had an increased risk of complications (OR 1.8, P < 0.0001; OR 1.5, P < 0.0001). High surgical caseload reduced nonroutine discharge by 30% (OR 0.7, P < 0.0001) and complications by 10% (OR 0.9, P < 0.0281). Conclusions: A 41%, or 178 cases per year, reduction in surgical excision of acoustic neuroma cases was observed during the period 2001–2007. A possible explanation for this trend includes increased use of stereotactic radiosurgery. Nonroutine discharge and complications after surgical excision have increased perhaps because of surgery being used for larger tumors. [Copyright &y& Elsevier]

Background and Aim: Hepatorenal syndrome (HRS) is a serious complication of advanced liver disease and carries a poor prognosis. Recent trials have indicated that terlipressin may be effective in reversing HRS. Our aim was to evaluate the efficacy of terlipressin therapy in reversing type 1 HRS defined as a serum creatinine <1.5 mg/dL during treatment. Methods: Randomized controlled trials in which patients with type 1 HRS received at least 3 days of terlipressin therapy and albumin in the intervention arm were included after a systematic search of the published English reports. Studies with other vasoconstrictor therapies in the control group were excluded. Results: A total of 223 patients with HRS type 1 in four different trials, were included in the final analysis. Alcohol-related cirrhosis was the most common underlying etiology. The risk ratio for reversal in type 1 HRS with terlipressin therapy was 3.66 (95% confidence interval 2.15–6.23). Recurrence of HRS was low (8%). Serious side-effects requiring discontinuation of therapy were seen only in 6.8% of patients on terlipressin therapy. There was a trend towards improved transplant-free survival at 90 days in the terlipressin group (relative risk 1.86 95% confidence interval 1.0–3.4, P = 0.05). Conclusions: Terlipressin is effective in reversing HRS type 1. Recurrence of HRS is rare with at least 14 days of therapy. Serious side-effects requiring discontinuation of therapy are less common. There appears to be a survival benefit in patients with HRS treated with terlipressin. [ABSTRACT FROM AUTHOR]

We present the case of a 72-year-old female with a major depressive episode who developed hyponatremia associated with bupropion. In reviewing the literature, there are only a few case reports which pertain to this topic. The clinical symptoms of hyponatremia can be misinterpreted as a worsening of the primary psychiatric illness and can lead to potentially serious consequences if not fully evaluated. We recommend that clinicians should be well aware of this side effect and that sodium levels should be checked within the first 2 weeks after initiating treatment in patients, especially those with additional risk factors for hyponatremia, such as older age, female sex, diuretic use, low BMI, and unexplained mental status changes at any time during treatment with antidepressants. The risk for hyponatremia associated with mirtazapine appears to be low and its use can be helpful in patients who have developed hyponatremia induced by other antidepressants and who experienced symptoms of weight loss and insomnia. [ABSTRACT FROM AUTHOR]

The increasingly appreciated prevalence of complicated stressor‐to‐phenotype associations in human disease requires a greater understanding of how specific stressors affect systems or interactome properties. Many currently untreatable diseases arise due to variations in, and through a combination of, multiple stressors of genetic, epigenetic, and environmental nature. Unfortunately, how such stressors lead to a specific disease phenotype or inflict a vulnerability to some cells and tissues but not others remains largely unknown and unsatisfactorily addressed. Analysis of cell‐ and tissue‐specific interactome networks may shed light on organization of biological systems and subsequently to disease vulnerabilities. However, deriving human interactomes across different cell and disease contexts remains a challenge. To this end, this opinion article links stressor‐induced protein interactome network perturbations to the formation of pathologic scaffolds termed epichaperomes, revealing a viable and reproducible experimental solution to obtaining rigorous context‐dependent interactomes. This article presents our views on how a specialized 'omics platform called epichaperomics may complement and enhance the currently available conventional approaches and aid the scientific community in defining, understanding, and ultimately controlling interactome networks of complex diseases such as Alzheimer's disease. Ultimately, this approach may aid the transition from a limited single‐alteration perspective in disease to a comprehensive network‐based mindset, which we posit will result in precision medicine paradigms for disease diagnosis and treatment. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding the case of 65-year-old African-American female who was diagnosed with lung adenocarcinoma and has been subjected to pemetrexed and carboplatin medication.

The authors report a case of successful management of right side hemidystonia with gamma knife radiosurgery. A 24-year-old male with a history of birth asphyxia subsequently developed worsening right-sided torsional hemidystonia which failed to respond to the medical management. MRI of the brain was unremarkable. Stereotactic gamma knife radiosurgery (GKRS) was performed to create a lesion in the left posteroventral globus pallidum. The patient gradually improved over a course of 18 months without any complication. He obtained 61% improvement in dystonia rating scale. Radiosurgical pallidotomy is often viewed with suspicion and functional neurosurgeons show reluctance in preferring it to stereotactic radio frequency lesioning or stimulation surgery. The authors would like to highlight the chances of not only control, but also cure of the disease with this cost-effective treatment modality. [ABSTRACT FROM AUTHOR]

The article discusses various aspects of the fecal microbiota (stool) transplantation process in which human feces is removed from a healthy donor and placed into another patient's intestine. According to the article, stool transplantation is used to treat difficult or recurrent Clostridium difficile infections. It states that in most cases, patients requiring stool transplantation procedures receive colonoscopies where clinicians transfer liquefied and filtered stool into the colon.

A letter to the editor in response to a research article related to the effectiveness of rectal vancomycin therapy in patients With clostridium difficile infection (CDI) published in a previous issue is presented.

Background: Microscopic colitis (MC) causes chronic diarrhea. It has two histologic subtypes: lymphocytic colitis (LC) and collagenous colitis (CC). Little is known about the natural progression of disease with time and with treatment. Objectives: We aimed to assess histological changes over time. Design: We designed a retrospective study including adults diagnosed with MC from January 1992 to January 2020 at Mayo Clinic. Methods: Pathology reports were reviewed until 31 October 2020. Histological assessments at least 8 weeks apart were considered as adequate follow-up. Histological change from one subtype to the other and resolution were tracked with univariate and multivariable Cox proportional hazards models. Results: Overall, 416 patients with a median age at diagnosis of 63.9 years with >1 histopathological assessment were identified. Histology at initial diagnosis was CC in 218 (52.4%) patients and LC in 198 (47.6%). No medications were associated with a histological change. However, histological resolution was more likely with the use of aspirin [hazard ratio (HR): 2.10, 95% confidence interval (CI): 1.34–3.31, p = 0.001) and proton-pump inhibitors (PPIs; HR: 2.01, 95% CI: 1.34–3.02, p = 0.001). Histological resolution was more likely with budesonide treatment (HR: 1.86, 95% CI: 1.16–3.00, p = 0.010) and less likely with mesalamine (HR: 0.40, 95% CI: 0.19–0.83, p = 0.014), compared to medications such as prednisone, loperamide, and bismuth. Patients with CC were less likely to change their histology compared to patients with LC (HR: 0.24, 95% CI: 0.14–0.42, p < 0.001). There was no difference in histological resolution between the two subtypes (HR: 0.70, 95% CI: 0.47–1.05, p = 0.084). Conclusion: Patients with LC have a higher chance of changing their histology as compared to CC. However, histological resolution was associated with the use of PPIs and aspirin, and treatment with budesonide. [ABSTRACT FROM AUTHOR]

Background: Microscopic colitis (MC) causes chronic diarrhea. It has two histologic subtypes: lymphocytic colitis (LC) and collagenous colitis (CC). Little is known about the natural progression of disease with time and with treatment. Objectives: We aimed to assess histological changes over time. Design: We designed a retrospective study including adults diagnosed with MC from January 1992 to January 2020 at Mayo Clinic. Methods: Pathology reports were reviewed until 31 October 2020. Histological assessments at least 8 weeks apart were considered as adequate follow-up. Histological change from one subtype to the other and resolution were tracked with univariate and multivariable Cox proportional hazards models. Results: Overall, 416 patients with a median age at diagnosis of 63.9 years with >1 histopathological assessment were identified. Histology at initial diagnosis was CC in 218 (52.4%) patients and LC in 198 (47.6%). No medications were associated with a histological change. However, histological resolution was more likely with the use of aspirin [hazard ratio (HR): 2.10, 95% confidence interval (CI): 1.34-3.31, 푝 = 0.001) and proton-pump inhibitors (PPIs; HR: 2.01, 95% CI: 1.34-3.02, 푝 = 0.001). Histological resolution was more likely with budesonide treatment (HR: 1.86, 95% CI: 1.16-3.00, 푝 = 0.010) and less likely with mesalamine (HR: 0.40, 95% CI: 0.19-0.83, 푝 = 0.014), compared to medications such as prednisone, loperamide, and bismuth. Patients with CC were less likely to change their histology compared to patients with LC (HR: 0.24, 95% CI: 0.14-0.42, 푝 < 0.001). There was no difference in histological resolution between the two subtypes (HR: 0.70, 95% CI: 0.47-1.05, 푝 = 0.084). Conclusion: Patients with LC have a higher chance of changing their histology as compared to CC. However, histological resolution was associated with the use of PPIs and aspirin, and treatment with budesonide. [ABSTRACT FROM AUTHOR]

Background: Ankle sprains are very common injuries which can lead to long-term pain, swelling and instability. Compression is often used in the treatment of these common injuries but is it effective and how best is it delivered? Methods: MEDLINE (1966-current), EMBASE (1980-current), Cochrane Library (2011:1) and MEDION were included in our search. Studies evaluating compression in the treatment of ankle sprains were included. Two authors independently reviewed potential studies according to a set eligibility criteria. Results: Twelve studies including 1,701 patients with ankle sprains were identified (level of evidence: four grade 1b; five grade 2b; three grade 4). Intermittent pneumatic compression (IPC), elastic tubular bandage and compression bandaging were all evaluated. Five of the 12 studies reported that compression therapy improves recovery after ankle injury, of which one evaluated IPC, and the remaining four elastic bandages (Elastoplast, class II elastic stockings, wool and crepe, focal compression with air stirrup). Five studies evaluating Tubigrip in ankle sprains concluded that Tubigrip has no positive effect on functional recovery and may increase the requirement for analgesia compared with no intervention. Conclusion: Compression may be an effective tool in the management of ankle injuries and has been shown to reduce swelling and improve quality of life in single studies. Definitive conclusions are hampered by the poor quality of evidence and the variety of treatments used. The most effective form of compression to treat ankle sprains or is yet to be determined. Adequately designed randomized control trials are clearly needed. [ABSTRACT FROM AUTHOR]

Background: Synthetic cannabinoids (SC) are recreational designer drugs intended to mimic delta-9-tetrahydrocannabinol while surreptitiously circumventing classification by the Drug Enforcement Administration.Case Report: A 50-year-old black male arrived in the Emergency Department transported by Emergency Medical Services (EMS) for altered mental status after complaining of chest pain associated with smoking SCs. EMS found the patient with an empty foil pack labeled "Scooby Snax Limited Edition Blueberry Potpourri." The patient was somnolent, but became agitated when stimulated and complained of chest pain. Vital signs were blood pressure 87/52 mm Hg and pulse 52 beats/min. The electrocardiogram demonstrated an inferior wall myocardial infarction. Coronary angiography identified an occluded obtuse marginal second branch that was successfully opened with a drug-eluting stent. The patient recovered uneventfully. Urine drug screen was negative for cocaine, and gas chromatography/mass spectrometry testing of the smoked material identified PB-22 and AMB-FUBINACA as the active ingredients. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Emergency physicians and cardiologists need to be aware that the mechanism of action of synthetic cannabinoids on the endocannabinoid system may result in acute ST-segment elevation myocardial infarction requiring percutaneous coronary intervention. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is one of the most prevalent neuroinflammatory illnesses, characterized by the progressive loss of neurons in the brain. Proinflammatory cytokines play a key role in initiating and perpetuating neuroinflammation, which can lead to the activation of glial cells and the deregulation of inflammatory pathways, ultimately leading to permanent brain damage. Currently, available drugs for PD mostly alleviate symptoms but do not target underlying inflammatory processes. There is a growing interest in exploring the potential of phytochemicals to mitigate neuroinflammation. Phytochemicals such as resveratrol, apigenin, catechin, anthocyanins, amentoflavone, quercetin, berberine, and genistein have been studied for their ability to scavenge free radicals and reduce proinflammatory cytokine levels in the brain. These plant-derived compounds offer a natural and potentially safe alternative to conventional drugs for managing neuroinflammation in PD and other neurodegenerative diseases. However, further research is necessary to elucidate their underlying mechanisms of action and clinical effectiveness. So, this review delves into the pathophysiology of PD and its intricate relationship with proinflammatory cytokines, and explores how their insidious contributions fuel the disease's initiation and progression via cytokine-dependent signaling pathways. Additionally, we tried to give an account of PD management using existing drugs along with their limitations. Furthermore, our aim is to provide a thorough overview of the diverse groups of phytochemicals, their plentiful sources, and the current understanding of their anti-neuroinflammatory properties. Through this exploration, we posit the innovative idea that consuming nutrient-rich phytochemicals could be an effective approach to preventing and treating PD. This schematic diagram illustrates the neuroprotective effects of phytochemicals extracted from natural sources. These phytochemicals reduce the production of proinflammatory cytokines from activated microglial cells, astrocytes, and damaged neuronal cells, thereby preventing the progression of Parkinson's disease (PD). [Display omitted] • Parkinson's disease is a prevalent neuroinflammatory illness that results in the loss of neurons in the brain. • Proinflammatory cytokines play a key role in initiating and perpetuating neuroinflammation, which can lead to permanent brain damage. • Current drugs for PD mostly alleviate symptoms but do not target underlying inflammatory processes. • Phytochemicals, such as resveratrol, apigenin, catechin, anthocyanins, amentoflavone, quercetin, berberine, and genistein, have been studied for their potential to reduce proinflammatory cytokine levels in the brain. • Phytochemicals offer a natural and potentially safe alternative to conventional drugs for managing neuroinflammation in PD and other neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

This JAMA Clinical Guidelines Synopsis summarizes the 2018 Infectious Diseases Society of America and Society for Healthcare Epidemiology of America recommendations on diagnosis and treatment of Clostridium difficile infection. [ABSTRACT FROM AUTHOR]

Induction of posterior vitreous detachment (PVD) by pharmacologic vitreolysis has been largely attempted through the use of enzymatic reagents. Ocriplasmin has been the only FDA-approved clinical reagent so far. Several adverse effects of ocriplasmin have emerged, however, and the search for alternative PVD-inducing reagents continues. Since i) collagen forms an important structural component of the vitreous, and ii) strong vitreo-retinal adhesions exist between the cortical vitreous and the internal limiting membrane (ILM) of the retina, an effective PVD-inducing reagent would require both, vitreous liquefaction, and concurrent dehiscence of vitreoretinal adhesion, without being toxic to retinal cells. We designed a combination of two reagents to achieve these two objectives; a triple helix-destabilizing collagen binding domain (CBD), and a fusion of RGD (integrin-binding) tripeptide with CBD (RCBD) to facilitate separation of posterior cortical vitreous from retinal surface. Based on in vitro, ex-vivo, and in vivo experiments, we show that a combination of CBD and RCBD displays potential for safe pharmacologic vitreolysis. Our findings assume significance in light of the fact that synthetic RGD-containing peptides have already been used for inhibition of tumor cell invasion. Proteins such as variants of collagen binding domains could have extended therapeutic uses in the future. [ABSTRACT FROM AUTHOR]

Objective: Suicidal thoughts and behaviors (STBs) are prevalent among youth with psychotic disorders (PD) relative to the general population. Recent research now suggests that STBs may present during the prodromal phase of the disease, or the clinical high risk (CHR) state. While this knowledge is important for the development of suicide prevention strategies in adolescent and adult populations, it remains unclear whether risk for suicide extends to children with or at risk for psychosis. The current study is an extension of previous work assessing STBs in youth across the psychosis continuum. We examine STBs in 37 CHR and PD children ages 7–13 years old, and further explore the prodromal symptom correlates of STB severity among CHR children. Results: CHR and PD children endorsed STBs with a frequency and severity similar to what is observed in older CHR and PD populations. A number of children had never previously vocalized their suicidal plans or intent. Among CHR children, Social Anhedonia and Odd Behavior or Appearance were significantly correlated with STB severity. These findings underscore the importance of screening for STBs even in young children presenting with psychotic symptoms. [ABSTRACT FROM AUTHOR]

Background: Management of metastatic bone disease of the extremities (MBD-E) is challenging, and surgical directions pose significant implications for overall patient morbidity and mortality. Recent literature reviews on the surgical management of MBD-E present a paucity of high-level evidence and global inconsistencies in study design. In order to steer productive research, a scoping review was performed to map and assess critical knowledge gaps.Methods: The Arksey and O'Malley framework for scoping studies was followed. A comprehensive literature search identified a large body of literature pertaining to the surgical management of MBD-E. Study data and meta-data was extracted and presented using descriptive analytics and a thematic framework. Literature gaps were identified and analyzed.Results: Three hundred eighty five studies from 1969 to 2017 were included. Studies were categorized into 11 separate themes, with the majority (63%) falling into the "surgical fixation strategies" theme, followed by "complications" at 7% and "prognosis and survival" at 6.2%. Less than 3% of studies were categorized in "patient related outcomes" or "epidemiology" themes. 89% of studies were retrospective and only 6 studies were of level 1 or 2 evidence. We identified a temporal increase in publication by decade, and all studies published on interventional radiology techniques or economic analyses were published after 2007 or 2009, respectively. 64.9% of studies were published in Europe and 20.3% were published in North America. Average patient age was 62 (± 5.2 years), and breast was the most common primary tumour (28%), followed by lung (17%) and kidney (15%). In terms of surgical location, 75% of operations involved the femur, followed by the humerus at 22% and tibia at 3%.Conclusions: We present a descriptive overview of the current published literature on the surgical management of MBD-E. Critical knowledge gaps have been identified through the development of a thematic framework. Consolidation of literary gaps must involve bolstered efforts towards patient and family-engaged research initiatives and assessment of patient-related surgical outcomes. Multi-disciplinary engagement in developing prospective research will also help guide evidence-based personalized practice for these patients. By building on existing comprehensive patient databases and registries, knowledge on survival and prognostic parameters can be greatly improved. [ABSTRACT FROM AUTHOR]

Background Fecal microbiota transplantation (FMT) is highly effective for treating recurrent Clostridium difficile infection (CDI) in observational studies (>90%), but cure rates in clinical trials are lower. We performed a systematic review and meta-analysis to assess the efficacy of FMT for recurrent CDI in open-label studies and clinical trials. Methods A systematic search from January 1978 to March 2017 was performed to include clinical trials of FMT for CDI. We analyzed CDI resolution by calculating weighted pooled rates (WPRs). Results Thirteen trials were included, comprising 610 patients with CDI treated with single FMT. Overall, 439 patients had clinical cure (WPR, 76.1%; 95% confidence interval (CI), 66.4%–85.7%). There was significant heterogeneity among studies (I 2 = 91.35%). Cure rates were lower in randomized trials (139/216 patients; WPR, 67.7%; 95% CI, 54.2%–81.3%) than in open-label studies (300/394 patients; WPR, 82.7%; 71.1%–94.3%) (P <.001). Subgroup analysis by FMT delivery modality showed lower cure rates with enema than colonoscopy (WPR, 66.3% vs 87.4%; P <.001) but no difference between colonoscopy and oral delivery (WPR, 87.4% vs 81.4%; P =.17). Lower rates were seen for studies including both recurrent and refractory CDI than for those including only recurrent CDI (WPR, 63.9% vs 79%; P <.001). Conclusions FMT was associated with lower cure rates in randomized trials than in open-label and in observational studies. Colonoscopy and oral route are more effective than enema for stool delivery. The efficacy also seems to be higher for recurrent than for refractory CDI. [ABSTRACT FROM AUTHOR]

Thrombopoietin (TPO), a hematopoietic growth factor produced predominantly by the liver, is essential for thrombopoiesis. Prevailing theory posits that circulating TPO levels are maintained through its clearance by platelets and megakaryocytes via surface c-Mpl receptor internalization. Interestingly, we found a two- to threefold decrease in circulating TPO in GPIbα-/- mice compared with wild-type (WT) controls, which was consistent in GPIbα-deficient human Bernard-Soulier syndrome (BSS) patients. We showed that lower TPO levels in GPIbα-deficient conditions were not due to increased TPO clearance by GPIbα-/- platelets but rather to decreased hepatic TPO mRNA transcription and production. We found that WT, but not GPIbα-/-, platelet transfusions rescued hepatic TPO mRNA and circulating TPO levels in GPIbα-/- mice. In vitro hepatocyte cocultures with platelets or GPIbα-coupled beads further confirm the disruption of platelet-mediated hepatic TPO generation in the absence of GPIbα. Treatment of GPIbα-/- platelets with neuraminidase caused significant desialylation; however, strikingly, desialylated GPIbα-/- platelets could not rescue impaired hepatic TPO production in vivo or in vitro, suggesting that GPIbα, independent of platelet desialylation, is a prerequisite for hepatic TPO generation. Additionally, impaired hepatic TPO production was recapitulated in interleukin-4/GPIbα--transgenic mice, as well as with antibodies targeting the extracellular portion of GPIbα, demonstrating that the N terminus of GPIbα is required for platelet-mediated hepatic TPO generation. These findings reveal a novel nonredundant regulatory role for platelets in hepatic TPO homeostasis, which improves our understanding of constitutive TPO regulation and has important implications in diseases related to GPIbα, such as BSS and auto- and alloimmune-mediated thrombocytopenias. [ABSTRACT FROM AUTHOR]

The recreational use of cannabis has sharply increased in recent years in parallel with its legalization and decriminalization in several countries. Commonly, the traditional cannabis has been replaced by potent synthetic cannabinoids and cannabimimetics in various forms. Despite overwhelming public perception of the safety of these substances, an increasing number of serious cardiovascular adverse events have been reported in temporal relation to recreational cannabis use. These have included sudden cardiac death, vascular (coronary, cerebral and peripheral) events, arrhythmias and stress cardiomyopathy among others. Many of the victims of these events are relatively young men with few if any cardiovascular risk factors. However, there are reasons to believe that older individuals and those with risk factors for or established cardiovascular disease are at even higher danger of such events following exposure to cannabis. The pathophysiological basis of these events is not fully understood and likely encompasses a complex interaction between the active ingredients (particularly the major cannabinoid, Δ9-tetrahydrocannabinol), and the endo-cannabinoid system, autonomic nervous system, as well as other receptor and non-receptor mediated pathways. Other complicating factors include opposing physiologic effects of other cannabinoids (predominantly cannabidiol), presence of regulatory proteins that act as metabolizing enzymes, binding molecules, or ligands, as well as functional polymorphisms of target receptors. Tolerance to the effects of cannabis may also develop on repeated exposures at least in part due to receptor downregulation or desensitization. Moreover, effects of cannabis may be enhanced or altered by concomitant use of other illicit drugs or medications used for treatment of established cardiovascular diseases. Regardless of these considerations, it is expected that the current cannabis epidemic would add significantly to the universal burden of cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Monomorphic ventricular tachycardia (VT) is an important cause of morbidity and mortality. Use and outcome data of catheter ablation for VT in nonischemic cardiomyopathy (NICM) are limited. Methods and results: We obtained data from the 2003–2014 National Inpatient Sample databases. We used propensity score matching to compare patients undergoing catheter ablation versus medical therapy of VT related to NICM, and described the temporal trends in utilization and in‐hospital outcomes of catheter ablation of VT in patients with NICM in the United States. From 2003 to 2014, of 133,529 patients hospitalized with the principal diagnosis of VT in NICM, 14,651 (11.0%) underwent catheter ablation. In this period, there was an increasing trend in utilization of catheter ablation (9.3% in 2003–2004 to 12.1% in 2003–2014, adjusted OR [per year], 1.12; 95% CI, 1.08–1.16; Ptrend < 0.001). After propensity score matching, in‐hospital mortality occurred in 172 of 14,318 (1.2%) patients in the catheter ablation group, compared with 297 of 14,156 (2.1%) of patients undergoing medical therapy (47% lower; 43% relative difference [adjusted OR, 0.53; 95% CI, 0.43–0.66]). Conclusions: In patients with NICM, catheter ablation of VT is associated with lower in‐hospital mortality compared with those managed medically. The utilization rates of CA for VT related to NICM have increased in the past decade. Adequately powered randomized trials will be necessary to confirm these findings. [ABSTRACT FROM AUTHOR]

Background. The choice of antibiotics for systemic infections in patients with a high risk of Clostridium difficile infection (CDI) remains a clinical practice dilemma. Although some studies suggest that tetracyclines may be associated with a lower risk of CDI than other antibiotics, other results are conflicting. We conducted a systematic review and metaanalysis of studies that assessed the risk of CDI with tetracyclines compared to other antibiotics. Methods. We conducted a systematic search of Medline, Embase, and Web of Science from January 1978 through December 2016 to include studies that assessed the association between tetracycline use and risk of CDI. Weighted summary estimates were calculated using generalized inverse variance with a random-effects model using RevMan 5.3. Study quality was assessed using the Newcastle-Ottawa scale. Results. Six studies (4 case control, 2 cohort) with patient recruitment between 1993 and 2012 were included. Metaanalysis using a random-effects model, demonstrated that tetracyclines were associated with a decreased risk of CDI (odds ratio [OR], 0.62; 95% confidence interval [CI], 0.47-0.81; P < .001). There was significant heterogeneity, with an I2 of 53% with no publication bias. Subgroup analysis of studies that evaluated the risk of CDI with doxycycline alone also demonstrated a decreased risk of CDI (OR, 0.55; 95% CI, 0.40-0.75; P < .001). Conclusions. Metaanalyses of existing studies suggest that tetracyclines may be associated with a decreased risk of CDI compared with other antimicrobials. It may be reasonable to use tetracyclines whenever appropriate to decrease CDI associated with antibiotic use. [ABSTRACT FROM AUTHOR]

The purpose of our article is to assess the current understanding of Indian spice, curcumin, against amyloid-β (Aβ)-induced toxicity in Alzheimer's disease (AD) pathogenesis. Natural products, such as ginger, curcumin, and gingko biloba have been used as diets and dietary supplements to treat human diseases, including cancer, cardiovascular, respiratory, infectious, diabetes, obesity, metabolic syndromes, and neurological disorders. Products derived from plants are known to have protective effects, including anti-inflammatory, antioxidant, anti-arthritis, pro-healing, and boosting memory cognitive functions. In the last decade, several groups have designed and synthesized curcumin and its derivatives and extensively tested using cell and mouse models of AD. Recent research on Aβ and curcumin has revealed that curcumin prevents Aβ aggregation and crosses the blood-brain barrier, reach brain cells, and protect neurons from various toxic insults of aging and Aβ in humans. Recent research has also reported that curcumin ameliorates cognitive decline and improves synaptic functions in mouse models of AD. Further, recent groups have initiated studies on elderly individuals and patients with AD and the outcome of these studies is currently being assessed. This article highlights the beneficial effects of curcumin on AD. This article also critically assesses the current limitations of curcumin's bioavailability and urgent need for new formulations to increase its brain levels to treat patients with AD. [ABSTRACT FROM AUTHOR]

Tricuspid regurgitation (TR) presents as either primary valve pathology or secondary to pulmonary or left-sided heart disease. Severe TR portends a worse prognosis independent of age, right ventricular size and function, severe left ventricular dysfunction, and increased pulmonary arterial pressures. Surgical treatment for TR has mostly been limited to patients undergoing mitral valve repair since those at high surgical risk are not candidates for traditional TR surgery. For these patients, minimally invasive techniques could be of great benefit, yet these techniques have been slow to develop because of the various anatomic and physiological aspects of the tricuspid valve apparatus. Several promising new techniques are currently undergoing clinical investigation, including caval valve implantation, percutaneous tricuspid annuloplasty techniques (Trialign, TriCinch, Cardioband), edge-to-edge repair with the MitraClip system, the FORMA device, and the GATE tricuspid Atrioventricular Valved Stent. Further evaluation of their safety and long-term efficacy is warranted prior to commercial approval and widespread adoption. [ABSTRACT FROM AUTHOR]

Study Design: Retrospective study. Purpose: The aim of this study was to analyze various diagnostic tools, including GeneXpert, for the management of tuberculosis of the spine. Overview of Literature: Traditional diagnostic methods of microscopy, histology, and culture have low sensitivity and specificity for the management of tuberculosis of the spine. Methods: Of the 262 treated cases of spinal tuberculosis, data on 1 year follow-up was available for 217 cases. Of these, only 145 cases with a confirmed diagnosis were selected for retrospective analysis. Results: In 145 of the 217 patients (66.80%), diagnosis was confirmed on the basis of a culture. Of the 145 patients with a confirmed diagnosis, 98 (66.20%) patients were diagnosed on the basis of clinical presentation, whereas 123 (84.8%) exhibited a typical magnetic resonance imaging (MRI) picture. In 99 surgically treated patients, the diagnosis was confirmed on the basis of an intraoperative tissue biopsy. Among the 46 patients treated conservatively, 35 underwent a transpedicular biopsy, 4 patients underwent computed tomography-guided biopsy, 6 patients were diagnosed on the basis of material obtained from a cold abscess, and 1 patient underwent an open biopsy. The sensitivity of the culture for the detection of Mycobacterium tuberculosis was 66.80% (145/217) in our patients. Among the cases in which GeneXpert was used, the sensitivity for the detection of Mycobacterium tuberculosis was 93.4% (43/46). Moreover, the sensitivity of GeneXpert to detect rifampicin resistance was 100% (7/7) in our study. Conclusions: Majority of the patients with tuberculosis of the spine can be diagnosed on the basis of a typical radiological presentation via MRI. In our study, 84.8% cases exhibited typical MRI findings. For patients presenting with atypical MRI features, a rapid and accurate diagnosis is possible by combining GeneXpert with MRI. The combined use of MRI and GeneXpert is a rapid and highly sensitive tool to diagnose tuberculosis and rifampicin resistance in patients with tuberculosis of the spine. Furthermore, we achieved a 97.9% sensitivity for the detection of Mycobacterium tuberculosis and 100% sensitivity for the detection of rifampicin resistance in our study. [ABSTRACT FROM AUTHOR]

Aim: Platelet function is intricately linked to the pathophysiology of critical Illness, and some studies have shown that antiplatelet therapy (APT) may decrease mortality and incidence of acute respiratory distress syndrome (ARDS) in these patients. Our objective was to understand the efficacy of APT by conducting a meta-analysis.Materials and Methods: We conducted a meta-analysis using PubMed, Central, Embase, The Cochrane Central Register, the ClinicalTrials.gov Website, and Google Scholar. Studies were included if they investigated critically ill patients receiving antiplatelet therapy and mentioned the outcomes being studied (mortality, duration of hospitalization, ARDS, and need for mechanical ventilation).Results: We found that there was a significant reduction in all-cause mortality in patients on APT compared to control (odds ratio [OR]: 0.83; 95% confidence interval [CI]: 0.70-0.97). Both the incidence of acute lung injury/ARDS (OR: 0.67; 95% CI: 0.57-0.78) and need for mechanical ventilation (OR: 0.74; 95% CI: 0.60-0.91) were lower in the antiplatelet group. No significant difference in duration of hospitalization was observed between the two groups (standardized mean difference: -0.02; 95% CI: -0.11-0.07).Conclusion: Our meta-analysis suggests that critically ill patients who are on APT have an improved survival, decreased incidence of ARDS, and decreased need for mechanical ventilation. [ABSTRACT FROM AUTHOR]

Keeping in view the confines allied with presently accessible antitumor agents and success of C 5 -curcuminoid based bifunctional hybrids as novel antitubulin agnets, molecular hybrids of C 5 -curcuminoid and coumarin tethered by triazole ring have been synthesized and investigated for in-vitro cytotoxicity against THP-1, COLO-205, HCT-116 and PC-3 human tumor cell lines. The results revealed that the compounds A-2 to A-9, B-2, B-3, B-7 showed significant cytotoxic potential against THP-1, COLO-205 and HCT-116 cell lines, while the PC-3 cell line among these was found to be almost resistant. Structure activity relationship revealed that the nature of Ring X and the length of carbon-bridge (n) connecting triazole ring with coumarin moiety considerably influence the activity. Methoxy substituted phenyl ring as Ring X and two carbon-bridges were found to be the ideal structural features. The most potent compounds (A-2, A-3 and A-7) were further tested for tubulin polymerization inhibition. Compound A-2 was found to significantly inhibit the tubulin polymerization (IC 50 = 0.82 μM in THP-1 tumor cells). The significant cytotoxicity and tubulin polymerization inhibition by A-2 was further rationalized by docking studies where it was docked at the curcumin binding site of tubulin. [ABSTRACT FROM AUTHOR]

Purpose: Adjuvant radiation therapy, which has proven benefit against breast cancer, has historically been associated with an increased incidence of ischemic heart disease. Modern techniques have reduced this risk, but a detailed evaluation has not recently been conducted. The present study evaluated the effect of current radiation practices on ischemia-related cardiac events and procedures in a population-based study of older women with nonmetastatic breast cancer.Methods and Materials: A total of 29,102 patients diagnosed from 2000 to 2009 were identified from the Surveillance, Epidemiology, and End Results-Medicare database. Medicare claims were used to identify the radiation therapy and cardiac outcomes. Competing risk models were used to assess the effect of radiation on these outcomes.Results: Patients with left-sided breast cancer had a small increase in their risk of percutaneous coronary intervention (PCI) after radiation therapy-the 10-year cumulative incidence for these patients was 5.5% (95% confidence interval [CI] 4.9%-6.2%) and 4.5% (95% CI 4.0%-5.0%) for right-sided patients. This risk was limited to women with previous cardiac disease. For patients who underwent PCI, those with left-sided breast cancer had a significantly increased risk of cardiac mortality with a subdistribution hazard ratio of 2.02 (95% CI 1.23-3.34). No other outcome, including cardiac mortality for the entire cohort, showed a significant relationship with tumor laterality.Conclusions: For women with a history of cardiac disease, those with left-sided breast cancer who underwent radiation therapy had increased rates of PCI and a survival decrement if treated with PCI. The results of the present study could help cardiologists and radiation oncologists better stratify patients who need more aggressive cardioprotective techniques. [ABSTRACT FROM AUTHOR]