Established Treatment Algorithms Research Articles

Male secretory breast cancer: case in a 6-year-old boy with a peculiar gene duplication and review of the literature

Secretory breast cancer (SBC) is one of the rarest breast cancer (BC), representing the majority of BC in childhood. Nevertheless, it elicits a lot of interest both for the peculiar morphology and the characteristic genetic features. Currently, there is no consensus on optimal treatment strategy. Therefore, it is useful to report every case in order to establish treatment algorithms. We describe the case of a 6-year-old boy diagnosed with a SBC, with peculiar genomic and immunohistochemical features. Moreover, we carried out a review of the literature in order to analyze the present state of knowledge about this rare entity. To the best of our knowledge, there are only 120 cases published in literature, only 32 in males and only 2 younger than 6years. Furthermore, this one had peculiar genomic and immunohistochemical features. Indeed, even if SBC expresses basal-cell markers, our patient had a triple-negative tumor expressing both basal and luminal cell markers. Furthermore, the boy's genomic profile revealed not only positivity for the typical SBC's translocation t(12;15), but also for a 3q28 duplication, found in his father (healthy) and paternal grandfather (with a previous BC). None were positive for BRCA mutation. This locus includes only one gene encoding for a growth factor recently linked to Early Infantile Epileptic Encephalopathy-47 and Idiopathic ventricular tachycardia. Even if the literature does not provide evidence of a pathogenic role it is not possible to exclude a cancer-predisposing activity. SBC is a rare type of BC, characterized by triple-negative features with an unexpectedly good prognosis. More data are needed to fully understand the behavior of this cancer and genomic profiling could be helpful in improving its diagnosis and management.

Phase 1 study to evaluate the safety and tolerability of MEDI4736 (durvalumab, DUR) + tremelimumab (TRE) in patients with advanced solid tumors.

3069 Background: DUR is a human IgG1 monoclonal antibody (mAb) that blocks PD-L1. TRE is a human IgG2 mAb inhibitor of CTLA-4. Blocking these checkpoints can result in antitumor activity in some solid tumors. The targets for DUR and TRE are non-redundant, providing sound rationale for clinical testing of the combination. Methods: This is an ongoing Phase 1, multicenter, open label study (NCT01975831) with a dose escalation (3+3 design) and subsequent expansion phase. Patients (pts) with renal cell carcinoma (RCC), cervical (CC), colorectal (CRC), non-triple-negative breast (NTNBC), ovarian (OC), non-small cell lung, or head and neck cancer are eligible. Primary endpoints are safety/tolerability and identification of maximum tolerated dose (MTD) of the combination. Secondary objectives include tumor response and progression-free/overall survival. Results: As of 16 Dec 2016, 105 pts were treated. DUR 1500 mg every 4 weeks (Q4W) and TRE 75 mg Q4W X 4 was the regimen used for opening the expansion phase. Dose-limiting toxicities were reported in 4 pts: diarrhea, colitis, abnormal liver function tests (abn LFTs), and hyponatremia. The majority of treatment-related AEs (TRAEs) were Grades (Gr) 1 and 2. TRAEs ≥ Gr 3 were reported in 12 pts; the majority were diarrhea/colitis (n = 5) and abn LFTs (n = 4) and responded to established treatment algorithms. There was 1 Gr 5 TRAE: multi organ failure. No new toxicities were identified. The preliminary responses by tumor type with n ≥ 10 pts are shown in the table below. Responses were seen in OC and RCC at the Cohort 2 dose escalation level (DUR 1/TRE 3 mg/kg). There were 4 cases of SD > 24 weeks: CC, n=2; CRC, n=1; OC, n=1. PD-L1 status was not tested. Conclusions: The DUR + TRE combination has a manageable safety profile, with preliminary evidence of clinical activity. These data support continued study of the combination therapy; the study is ongoing. Clinical trial information: NCT01975831. [Table: see text]

A Management Algorithm for Mitomycin C Induced Cystitis.

Background/Objective: A post-bladder tumor resection dose of MMC can reduce non-invasive papillary (pTa) bladder cancer recurrences by up to 40%; this treatment is recommended in both the AUA and EUA non-muscle-invasive bladder cancer guidelines. A common complication of this treatment is eosinophilic cystitis. Symptoms range from mild urinary frequency and urgency to debilitating pain and dysuria. Currently, there is no established treatment algorithm for MMC-induced cystitis.Methods: Members of the Urologic Surgery Quality Collaborative (USQC), a group composed of over 160 private and academic urologists, met to discuss the management of patients with cystitis following MMC therapy. They devised a treatment algorithm based on experiences of urologic oncologists and neurourologists to aid in the diagnosis and management of MMC-induced cystitis.Results: The assessment begins with urinalysis and culture, followed by cystoscopy. For mild symptoms, behavioral therapy, including timed voids, fluid restriction and Kegel exercises are trialed. If symptoms have not resolved, treatment with an antihistamine, followed by a combination of anticholinergic and alpha-blocker medications. For persistent symptoms or severe symptoms at presentation, a course of prednisone plus antihistamine is prescribed. If symptoms are improving but have not resolved, this treatment is extended for a full 4 weeks prior to steroid taper. If symptoms do not improve, any visible bladder ulcerations are resected intraoperatively followed by an additional course of prednisone and antihistamine. Intravesical DMSO instillations and intra-ulcer steroid injection can be used as a final effort to treat this condition.Conclusion: We present the first formal management algorithm with escalating treatment intensity tailored to patient symptoms.

Postconcussion Syndrome: Neuropsychological Evaluation and Management

It has estimated that between 10% and 50% of people suffering a mild traumatic brain injury (mTBI) do not recover as expected. They often exhibit physical, cognitive, and psychological sequelae that seem out of proportion to the severity of the initial injury, and symptoms may persist for 1 year or more postinjury. People exhibiting this symptom pattern after mTBI often meet criteria for a diagnosis of postconcussion syndrome (PCS). Management of patients with PCS poses many potential challenges for the clinician. There is no clearly established treatment algorithm for PCS, and symptoms are highly variable in individual patients. In many cases, confounding social issues such as litigation or workers' compensation involvement are present. These issues further cloud the clinical picture and may have an impact on patient treatment response. Neuropsychological approaches to the evaluation and management of this complex patient population are commonly used conjointly with medical modalities. This article reviews common issues and controversies in PCS from the perspective of the assessment and management of cognitive and psychological symptoms. [ Psychiatr Ann . 2017;47(2):92–96.]

Contracted Nose after Silicone Implantation: A New Classification System and Treatment Algorithm.

BackgroundSilicone implants are frequently used in augmentation rhinoplasty in Asians. A common complication of silicone augmentation rhinoplasty is capsular contracture. This is similar to the capsular contracture after augmentation mammoplasty, but a classification for secondary contracture after augmentation rhinoplasty with silicone implants has not yet been established, and treatment algorithms by grade or severity have yet to be developed.MethodsPhotographs of 695 patients who underwent augmentation rhinoplasty with a silicone implant from May 2001 to May 2015 were analyzed. The mean observation period was 11.4 months. Of the patients, 81 were male and 614 were female, with a mean age of 35.9 years. Grades were assigned according to postoperative appearance. Grade I was a natural appearance, as if an implant had not been inserted. Grade II was an unnatural lateral margin of the implant. Clearly identifiable implant deviation was classified as grade III, and short nose deformation was grade IV.ResultsGrade I outcomes were found in 498 patients (71.7%), grade II outcomes in 101 (14.5%), grade III outcomes in 75 (10.8%), and grade IV outcomes in 21 patients (3.0%). Revision surgery was indicated for the 13.8% of all patients who had grade III or IV outcomes.ConclusionsIt is important to clinically classify the deformations due to secondary contracture after surgery and to establish treatment algorithms to improve scientific communication among rhinoplasty surgeons. In this study, we suggest guidelines for the clinical classification of secondary capsular contracture after augmentation rhinoplasty, and also propose a treatment algorithm.

Ageing and sexuality

Sexuality is a dimension that concerns human health with profound implications not only in the biological and psychological aspects, but also in the social and cultural dimensions, affecting all ages of life. Sexuality in old age is still conditioned by biases, prejudices and from a stereotyped vision, which considered older people as “asexual”, in spite of several studies and surveys showing that older persons have sexual potential to express. In population surveys, a fair number of men and women aged over 60 years reported having sex at least once a month. The most influential predictor of sexual activity seems to be the physical health in older men, and the quality of the relationship in older women. The most common sexual disorders are erectile dysfunction and delayed ejaculation in older men, and reduced sexual interest, arousal disorder, female orgasmic disorder, genitopelvic pain and ailments of penetration in older women. A careful evaluation can identify the presence and severity of disorders in different phases of the sexual response cycle. The management of sexual dysfunction in older people may include reassurance, education, sex therapy and/or the use of drugs in specific cases. Sexuality in patients with dementia may arise as inappropriate sexual behaviour (ISB) due to behavioural disinhibition. Manifestations of ISB can be very distressing for family members and other caregivers and can present substantial challenges for staff and health care providers in long term care. Although there is no established treatment algorithm for dementia-related ISB, there are various non-pharmacological and pharmacological treatments, which can help in the management of these patients.

Salvaging the Infected Breast Tissue Expander: A Standardized Multidisciplinary Approach.

Background:Infections of breast tissue expander (TE) are complex, often requiring TE removal and hospitalization, which can delay further adjuvant therapy and add to the overall costs of breast reconstruction. Therefore, to reduce the rate of TE removal, hospitalization, and costs, we created a standardized same-day multidisciplinary outpatient quality improvement protocol for diagnosing and treating patients with early signs of TE infection.Methods:We prospectively evaluated 26 consecutive patients who developed a surgical site infection between February 2013 and April 2014. On the same day, patients were seen in the Plastic Surgery and Infectious Diseases clinics, underwent breast ultrasonography with or without periprosthetic fluid aspiration, and were prescribed a standardized empiric oral or intravenous antimicrobial regimen active against biofilm-embedded microorganisms. All patients were managed as per our established treatment algorithm and were followed up for a minimum of 1 year.Results:TEs were salvaged in 19 of 26 patients (73%). Compared with TE-salvaged patients, TE-explanted patients had a shorter median time to infection (20 vs 40 days; P = 0.09), a significantly higher median temperature at initial presentation [99.8°F; interquartile range (IQR) = 2.1 vs 98.3°F; IQR = 0.4°F; P = 0.01], and a significantly longer median antimicrobial treatment duration (28 days; IQR = 27 vs 21 days; IQR = 14 days; P = 0.05). The TE salvage rates of patients whose specimen cultures yielded no microbial growth, Staphylococcus species, and Pseudomonas were 92%, 75%, and 0%, respectively. Patients who had developed a deep-seated pocket infection were significantly more likely than those with superficial cellulitis to undergo TE explantation (P = 0.021).Conclusions:Our same-day multidisciplinary diagnostic and treatment algorithm not only yielded a TE salvage rate higher than those previously reported but also decreased the rate of hospitalization, decreased overall costs, and identified several clinical scenarios in which TE explantation was likely.

Soft Tissue Sarcomas of the Arm - Oncosurgical and Reconstructive Principles within a Multimodal, Interdisciplinary Setting.

Soft tissue sarcomas of the upper extremity represent a severe threat for the patient and a difficult task for the treatment team. Due to the complex anatomy of the arm, most sarcomas involve valuable functional structures. Nonetheless, a large portion of the patients can be treated in a limb-sparing manner, and surgery is the mainstay of local tumor control. This review gives an overview of the disease entities and their epidemiology, on necessary patient work-up, staging, and imaging modalities, as well as the importance of interdisciplinary decision-making. The surgical therapies and principles of tumor excision are outlined, as well as reconstructive options. Furthermore, adjuvant treatments are discussed with a special focus on the various application techniques for radiation therapy. In spite of established treatment algorithms, each case is an individual challenge and individually tailored therapy is required. This aspect is illustrated by presenting three comprehensive cases demonstrating useful strategies. A summary of the relevant literature is given.

High central venous saturation after cardiac surgery is associated with increased organ failure and long-term mortality: an observational cross-sectional study

IntroductionCentral venous saturation (ScvO2) monitoring has been suggested to address the issue of adequate cardiocirculatory function in the context of cardiac surgery. The aim of this study was to determine the impact of low (L) (<60%), normal (N) (60%-80%), and high (H) (>80%) ScvO2 measured on intensive care unit (ICU) admission after cardiac surgery.MethodsWe conducted a retrospective, cross-sectional, observational study at three ICUs of a university hospital department for anaesthesiology and intensive care. Electronic patient records of all adults who underwent cardiac surgery between 2006 and 2013 and available admission measurements of ScvO2 were examined. Patients were allocated to one of three groups according to first ScvO2 measurement after ICU admission: group L (<60%), group N (60%-80%), and group H (>80%). Primary end-points were in-hospital and 3-year follow-up survival.ResultsData from 4,447 patients were included in analysis. Low and high initial measurements of ScvO2 were associated with increased in-hospital mortality (L: 5.6%; N: 3.3%; H: 6.8%), 3-year follow-up mortality (L: 21.6%; N: 19.3%; H: 25.8%), incidence of post-operative haemodialysis (L: 11.5%; N: 7.8%; H: 15.3%), and prolonged hospital length of stay (L: 13 days, 9–22; N: 12 days, 9–19; H: 14 days, 9–21). After adjustment for possible confounding variables, an initial ScvO2 above 80% was associated with adjusted hazard ratios of 2.79 (95% confidence interval (CI) 1.565-4.964, P <0.001) for in-hospital survival and 1.31 (95% CI 1.033-1.672, P = 0.026) for 3-year follow-up survival.ConclusionsPatients with high ScvO2 were particularly affected by unfavourable outcomes. Advanced haemodynamic monitoring may help to identify patients with high ScvO2 who developed extraction dysfunction and to establish treatment algorithms to improve patient outcome in these patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-015-0889-6) contains supplementary material, which is available to authorized users.

MP26-02 A MANAGEMENT ALGORITHM FOR MITOMYCIN-C (MMC)

You have accessJournal of UrologyBladder Cancer: Non-invasive I1 Apr 2015MP26-02 A MANAGEMENT ALGORITHM FOR MITOMYCIN-C (MMC) Amy Luckenbaugh, MD David Miller, MD Alon Weizer, MD John Stoffel, andMD Jeffrey MontgomeryMD, MHSA Amy LuckenbaughAmy Luckenbaugh More articles by this author , David MillerDavid Miller More articles by this author , Alon WeizerAlon Weizer More articles by this author , John StoffelJohn Stoffel More articles by this author , and Jeffrey MontgomeryJeffrey Montgomery More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.1124AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES A post-bladder tumor resection dose of MMC can reduce stage Ta/T1 bladder cancer recurrences by up to 40%; this treatment is recommended in the AUA and EUA non-muscle-invasive bladder cancer guidelines. Complications from this therapy, though, are under-reported. Recent research demonstrated complications in up to 35% of patients following a single peri-operative dose MMC. A more common complication is an eosinophil-mediated cystitis. Currently, there is no established treatment algorithm for MMC-induced cystitis. METHODS Members of the Urologic Surgery Quality Collaborative (USQC) devised a treatment algorithm based on expert opinion to aid in the diagnosis and management of MMC-induced cystitis. The USQC is a group composed of over 160 private and academic urologists from Michigan, Ohio, Virginia, Indiana and Tennessee. The treatment algorithm developed involves sequential escalation of the evaluation and treatment of MMC-induced cystitis and has been disseminated and implemented in USQC practices. RESULTS The figure shows the USQC algorithm. The assessment begins with a urinalysis and culture, followed by cystoscopy to rule out bladder perforation. Behavioral therapy, including timed voids, fluid restriction and Kegal exercises is trialed for 1 week. If symptoms have not resolved, treatment with an antihistamine (e.g. Diphenhydramine 25mg orally every 6 hours) is used for 1 week, followed by a combination of anticholinergic and alpha-blocker medications (e.g. Tolterodine LA 4mg and Tamsulosin 0.4mg orally daily) for 1 week. For persistent symptoms, a course of prednisone plus antihistamine is prescribed (60mg orally daily with a 6 day taper plus Diphenhydramine as above) for 2 weeks; if symptoms are improving but not resolved, this treatment is extended for a full 4 weeks. If symptoms still persist, any visible bladder ulcerations should be resected followed by an additional 2 week course of steroid and antihistamine. For refractory symptoms, intravesical DMSO followed by hyperbaric oxygen can be trialed. CONCLUSIONS We present the first algorithm for the treatment of MMC-induced cystitis. This algorithm is now used by members of the USQC for management of MMC-induced cystitis when it occurs. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e293-e294 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Amy Luckenbaugh More articles by this author David Miller More articles by this author Alon Weizer More articles by this author John Stoffel More articles by this author Jeffrey Montgomery More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Diabetes mellitus and severe mental illness: mechanisms and clinical implications.

The prevalence of diabetes mellitus is twofold to threefold higher in people with severe mental illness (SMI) than in the general population, with diabetes mellitus affecting ∼12% of people receiving antipsychotics. The consequences of diabetes mellitus are more severe and frequent in people with SMI than in those without these conditions, with increased rates of microvascular and macrovascular complications, acute metabolic dysregulation and deaths related to diabetes mellitus. Multiple complex mechanisms underlie the association between diabetes mellitus and SMI; these mechanisms include genetic, environmental and disease-specific factors, and treatment-specific factors. Although antipsychotics are the mainstay of treatment in SMI, a causative link, albeit of uncertain magnitude, seems to exist between antipsychotics and diabetes mellitus. The principles of managing diabetes mellitus in people with SMI are similar to those for the general population and should follow currently established treatment algorithms. Lifestyle interventions are needed to reduce incident diabetes mellitus. In addition, improved uptake of opportunities to screen for this disease will reduce the high prevalence of undiagnosed diabetes mellitus. Currently, people with SMI receive poorer treatment for diabetes mellitus than the general population. Thus, health-care professionals in primary care, diabetes mellitus services and mental health teams have a responsibility to ensure that patients with SMI are not disadvantaged.

Pediatric elbow injuries in athletes.

Elbow injuries in pediatric and adolescent population represent a spectrum of pathology that can range from medial tension injuries to posterior shear injuries. Elbow injuries in this population continue to rise in parallel with the increase in youth participation in sports both throughout the calendar year and across multiple sports. Many of these injuries are noncontact and are attributed to overuse. Evaluation and management of youth and adolescent athletic elbow injuries requires knowledge of developmental anatomy, injury pathophysiology, and established treatment algorithms. Furthermore, risk factors contributing to elbow injuries must be recognized, with education and recommendations for safe play continually advocated. This education--of parents, athletes, and coaches--is paramount in reducing the climbing incidence of elbow injuries in our youth athletes.

763PD - Updated Overall Survival (Os) from the Phase 3 Trial, Ca184-043: Ipilimumab (Ipi) Vs Placebo (Pbo) in Patients with Post-Docetaxel Metastatic Castration-Resistant Prostate Cancer (Mcrpc)

ABSTRACT Aim: Ipi is a fully human monoclonal antibody that blocks cytotoxic T-lymphocyte antigen-4 (CTLA-4) to augment antitumor immune responses. The phase 3 trial, CA184-043, evaluated OS with radiotherapy (RT) followed by Ipi or Pbo in patients (pts) with advanced mCRPC. As reported previously, the primary endpoint was not met [HR (95% CI): 0.85 (0.72-1.00); P = 0.053] (Kwon ED, et al. Lancet Oncol. 2014; in press). Here, we report updated OS data with an additional year of follow-up from the primary analysis (2-yr minimum). Methods: 799 pts were randomized to receive a single dose of RT to bone metastases followed by either Ipi (N = 399) or Pbo (N = 400). Updated OS analysis was performed on the intention-to-treat (ITT) population. Prespecified and exploratory subset analyses based on Kaplan-Meier/Cox methodology were performed using known prognostic factors for OS in mCRPC. Results: Updated OS analysis (ITT population), with survival rates up to 3 yrs, was consistent with the primary analysis (Table). Also consistent with previous reports, prespecified subgroup analyses suggest greater activity in pts with lower disease burden [e.g., Ipi vs. Pbo, pts with (HR 1.17, 0.89–1.53) or without (0.74, 0.61–0.89) visceral metastases]. The safety profile with extended follow-up was similar to that reported previously, which included immune-related AEs (irAEs) (gastrointestinal, dermatologic, endocrine, and hepatic). Most irAEs were manageable with established Ipi treatment algorithms. Ipi + RT Pbo + RT Median OS (95% CI) 11.2 mo (9.6–12.6) 10.0 mo (8.4–11.2) HR (95% CI) 0.84 (0.72–0.98) Log-rank * P = 0.03 1-Year OS rate 47% 41% 2-Year OS rate 25% 17% 3-Year OS rate ** 12% 6% * Exploratory analysis (for descriptive purposes only). ** 27 pts (17 Ipi, 10 Pbo) included in the risk set at 36 mo. Conclusions: With an additional year of follow-up, the activity observed for Ipi + RT in post-docetaxel mCRPC pts is maintained. In addition, subgroup analyses suggest pts with lower disease burden may be more likely to benefit from Ipi treatment. Long-term OS and Ipi benefit in mCRPC pts with lower disease burden (i.e., no visceral metastases) will be evaluated in the ongoing phase 3 study, CA184-095. Disclosure: K. Fizazi: Advisory board: Bristol-Myers Squibb; C.G. Drake: Sponsored research: Aduro Biotech, Bristol-Myers Squibb, Janssen; consultant: Bristol-Myers Squibb, Compugen, Dendreon, Pfizer, Roche/Genentech, NexImmune; .D. Kwon: Advisory board: NCI GU Steering Committee. Dr. Kwon and Mayo Clinic have licensed technology related to immunotherapy to Bristol-Myers Squibb, MedImmune, Amplimune, and Medarex; A.J. van den Eertwegh: Advisory board: Bristol-Myers Squibb, Astellas, Janssen-Cilag B.V., Sanofi. Honoraria for presentations about ipilimumab/prostate cancer: Bristol-Myers Squibb, Sanofi, Janssen-Cilag; H.I. Scher: Ad board:Dendreon,Endo/Orion,Genentech,Novartis,OrthoBiotech,Aragon,BMS,Celgene,Exelixis,FoundationMedicine,Janssen,JJ Spons.research: Aragon,BMS,Exelixis,Janssen,Medivation; T.M. Beer: Corporate-sponsored research: Bristol-Myers Squibb; M.B. McHenry: Employee of Bristol-Myers Squibb and owns Bristol-Myers Squibb stock; D. Liu: Employee of Bristol-Myers Squibb; owns Bristol-Myers Squibb stock; W.R. Gerritsen: Advisory board: Aglaia Biomedical Ventures, Amgen, Bayer, Bristol-Myers Squibb, Ipsen, Janssen, Merck, and Sanofi; speaker's honoraria: Astellas, Bristol-Myers Squibb, and Janssen; C. Logothetis: Corporate-sponsored research: Johnson & Johnson; honoraria: Johnson & Johnson.All other authors have declared no conflicts of interest.

Characterization of immune-related adverse events (irAEs) in a phase 3 trial of ipilimumab (Ipi) versus placebo (Pbo) in post-docetaxel mCRPC.

52 Background: Ipi enhances antitumor immunity by blocking cytotoxic T-lymphocyte antigen-4. We recently reported the results of CA184-043, a phase 3 study of post-docetaxel mCRPC with Ipi vs Pbo, following single-dose radiotherapy (RT). While the study did not meet the primary endpoint of improving overall survival (HR=0.85, p=0.053), Ipi demonstrated antitumor activity in other efficacy endpoints, including progression-free survival. The present analyses further characterize the safety profile of Ipi in this study. Methods: Safety was evaluated for all treated patients (pts; N=393 for Ipi 10 mg/kg, N=396 for Pbo) starting from first study dose and ending 70 days after the last study dose, including maintenance dosing. Results: Any grade (Gr) irAEs occurred in 63.4% and 21.7% of pts in the Ipi and Pbo arms, respectively. Most common Gr 3/4 irAEs were gastrointestinal (GI) (18.1%; mostly diarrhea and colitis). Gr 3/4 liver irAEs (4.6%) were mostly elevations in AST or ALT. Other Gr 3/4 irAEs were uncommon: endocrine (2.0%), skin (1.0%), and neurological (0.3%). Among Ipi-treated pts, there were no meaningful differences in the frequency or severity of GI AEs between those who received baseline pelvic RT and those who did not (n=141 vs 252; any Gr 77.3% vs 69.8%; Gr 3/4 25.5% vs 21.8%, respectively). There were 5 GI perforations in the Ipi arm (3 within 70 days of last dose [2 related, 1 unrelated], 2 after 70 days of last dose, both related), and none in the Pbo arm. Deaths due to study drug toxicity, as per the investigators, occurred in 4 pts (4, Ipi and 0, Pbo). Conclusions: In this study of Ipi in mCRPC, the most frequent severe irAEs were diarrhea and colitis. Most irAEs were manageable using established treatment algorithms. Clinical trial information: NCT00861614. [Table: see text]

Characteristics and treatment outcomes of 69 cases with early prosthetic joint infections of the hip and knee

Early prosthetic joint infection (PJI) can be treated with an intensive surgical debridement and implant retention (DAIR) of the prosthesis if (1) the prosthesis is stable, (2) the pathogen is not a difficult-to-treat microorganism, (3) symptoms have lasted for <3 weeks and (4) a sinus tract is absent. We retrospectively evaluated the treatment outcome of early PJI in the hip and knee in a single orthopaedic centre. An early PJI was defined as a prosthesis infection within 3 months after primary implantation or revision surgery for a non-infectious cause. We identified 69 patients with confirmed early PJI, with a median age of 71 (range 33-84) years. Only 64 % presented with ≥2 acute signs of infection. The most commonly isolated bacteria were coagulase-negative staphylococci (38 %) and Staphylococcus aureus (25 %). Surgical procedures included DAIR (50 cases, 69 %) and two-stage exchange (19 cases, 31 %). At last follow-up, five of remaining living 67 patients (7.5 %) had a relapse of infection. The overall relapse-free survival of the prosthesis after 2 years was 92.3 % (95 % confidence interval 82-97 %) with no significant difference between DAIR and exchange of prosthesis. Our data suggest that an early PJI should be treated with DAIR as a less invasive procedure whenever possible according to the established treatment algorithm.

Noninfectious Granulomatous Dermatitides: A Review of 8 Disorders (Part 1 of 3)

In this review we focus on 2 of the noninfectious granulomatous dermatitides, granuloma annulare and interstitial granulomatous dermatitis (the remaining 6 will be discussed in Parts 2 and 3), with an overview of their clinical and histological presentations, differential diagnoses, and treatment options. The disorders we discuss are polymorphic in their clinical and histopathological presentations, follow chronic or undulating disease courses, and are typically recalcitrant to therapeutic interventions. Although the clinical history may be helpful, careful and thorough histopathological examination is required. Established treatment algorithms for these disorders are lacking, and no randomized, placebo-controlled studies have been published. Future investigations should focus on the evaluation of larger cohorts, not only to establish treatment recommendations in randomized, placebo-controlled trials, but also to reach a greater understanding of disease pathogenesis and clinical-pathological presentation.

Cost‐Effective Management of Patients with Sinus Headache, Facial Pain, and Pressure: A Decision Analytic Approach

Objectives: 1) To study patients presenting to a tertiary otolaryngology clinic with primary complaints of sinus headache, facial pain, and/or pressure. 2) To perform a computer-based decision analysis of these patients to maximize treatment effectiveness and minimize cost. Methods: A computer-based decision analytic approach was used to model cost-effectiveness (CE) of treatment of 253 adult patients presenting to a tertiary ear, nose, and throat (ENT) clinic over a two-year period. Chief complaints were sinus headache and/or facial pain/pressure. Analysis of demographics and treatment data was performed. Management was classified into three categories: 1) maximal medical therapy (MMT) alone, 2) MMT followed by endoscopic sinus surgery (ESS) due to refractory disease, and 3) referral to neurology for pain without apparent sinus etiology. Established treatment algorithms were integrated with CPT based treatment costs to create a 66-point decision tree that provides a comprehensive picture of CE of various modes of treatment for facial pain. Results: For patients without evidence of sinus disease, referral to neurology for facial pain saved $33.61 per patient for pain management. ESS resulted in a significant improvement in CE only with demonstrable sinus disease (C/E=26.37; p=0.027). Other trends observed include a non-significant reduction in cost and effectiveness of using MMT first in patients without clinical evidence of sinus disease (C/E=12.98; p=0.064). Conclusions: Our model demonstrates favorable CE of determining the etiology of facial pain as early as possible and proceeding with MMT or with referral to neurology, accordingly. ESS should only be offered to patients with true sinus disease refractory to MMT.

Turned off and burned out: what will it take for "front-line" medicine to tune back in?

The United States is facing a severe shortage of physicians providing access at the front lines of care access. Specialties with provider shortages include general medicine, family medicine, and other fields providing longitudinal primary and comprehensive care.1,2 In fact, because nearly one-half of visits to subspecialists actually involve primary and general medical care services,3,4 the insufficient supply of front-line physicians to meet patient care demands may be even more extreme than current projections suggest. Despite this impending crisis, student and resident interest in these front-line longitudinal care fields has been stagnant at best in recent years and has declined drastically during the past 2 decades.5,6 For example, in 2012, only 6% of graduating medical students planned careers in family medicine.6 Additional data suggest only 2% of graduating medical students plan to practice general or primary care internal medicine,7 and only 1 in 5 internal medicine residents plans a career in general medicine after graduation.8

Ipilimumab in melanoma

Ipilimumab is a fully human monoclonal antibody directed against the cytotoxic T-lymphocyte antigen-4 receptor. Blocking cytotoxic T-lymphocyte antigen-4 signaling has been shown to enhance T-cell activation and to amplify T-cell-mediated immunity. Ipilimumab, either as a single agent or in combination with gp100 vaccination, significantly prolonged overall survival in a randomized Phase III trial in patients with disease progression after prior treatment when compared with gp100 alone. In previously untreated patients, the addition of ipilimumab to dacarbazine also significantly prolonged overall survival. The most common adverse events are immune related. Adherence to established treatment algorithms in patients with immune-related adverse events is advocated. Predictive factors for the activity of ipilimumab have not been identified but would be of great value in the selection of patients who are most likely to benefit from this innovative immunotherapy. Outstanding issues include the role of ipilimumab in the adjuvant treatment of patients who are at high risk for relapse, and the optimal treatment sequence for patients with BRAFV600 mutant melanoma, as small-molecule BRAF inhibitors have also been shown to improve the survival for this subgroup of patients.

Cauda Equina in the Setting of Thoracolumbar Trauma: Is Early Decompression Indicated?

Traumatic injuries to the thoracolumbar spine are common and can be associated with a neurologic deficit. Complete cord level injury and progressive neurologic compromise have established treatment algorithms. The management of traumatic thoracolumbar spine injuries with incomplete neurologic deficits, such as cauda equina and conus medullaris syndrome, is challenging and often controversial. Published animal models and clinical data, largely retrospective, provide conflicting information as to the necessity of surgical intervention and the timing of such surgical intervention in these patients. There is a clear need for quality prospective human data to conclusively resolve the issue of timing of surgery in patients with traumatic cauda equina and conus medullaris injury.