Malignant Self-Regard as an Overarching Framework for the Theory and Treatment of Depressive and Masochistic (Self-Defeating) Personalities.

ABSTRACT: Kernberg and McWilliams have spawned differing conceptualizations of the relationship between depressive and masochistic (self-defeating) personalities. Kernberg describes these personality styles as largely overlapping in features, whereas McWilliams accentuates important clinical differences that make up two distinct personalities. In this article, their theoretical perspectives are discussed and framed as more complementary than competitive. The malignant self-regard (MSR) construct is introduced and reviewed as an integrative self-representation that is shared by both depressive and masochistic personalities, as well as those often referred to as vulnerably narcissistic. We investigate developmental conflicts, motivations for perfectionism, countertransference patterns, and overall level of functioning as four primary clinical features through which a therapist may differentiate a depressive from a masochistic personality. We argue that depressive personalities tend to have more dependency-related conflicts and perfectionistic strivings motivated by lost object reunification, elicit more insidiously positive countertransference reactions in session, and are generally higher-functioning individuals. Masochistic personalities have more oedipal-related conflicts and perfectionistic strivings motivated by object control, elicit more aggressive countertransference reactions, and are relatively lower functioning. MSR is positioned as a bridge between Kernberg's and McWilliam's ideas. We close with a discussion of treatment implications for both disorders as well as how to understand and treat MSR.

Malignant Self-Regard: Overview and Future Directions.

ABSTRACT: Malignant self-regard (MSR) is a self-representation that encompasses the shared features of depressive personality disorder, masochistic/self-defeating personality disorder, depressive-masochistic personality, and vulnerable narcissism. In this review we begin by describing the construct's historical precursors, which begin in early psychoanalytic/dynamic theory, and then trace its development across iterations of the Diagnostic and Statistical Manual of Mental Disorders. Special attention is paid to differentiating MSR from vulnerable narcissism. We then consider MSR's place within transdiagnostic, transtheoretical, and dimensional models of personality pathology. We focus heavily on MSR's impact on various personality systems (e.g., thought and affect systems) and also on overall personality functioning. The empirical research on MSR in relation to these systems is thoroughly reviewed and largely supports its psychometric properties and clinical significance. We suggest that MSR may map onto the distress subfactor in the hierarchical taxonomy of psychopathology (HiTOP) and that MSR seems to occupy the shared internalizing space across the neurotic and borderline level of personality organization in Kernberg's model of personality disorders. We also identify four major directions for future research: the possible benefits of self-defeating tendencies that involve pathological narcissism and self-esteem; MSR's relationship to overall health and well-being; depressive states and MSR severity; and how MSR fits within the Alternative Model for Personality Disorders and the personality disorder framework of the International Classification of Diseases.

Exploring the Interface of Oncology and Palliative Care in Ireland

Aims To explore the integration and delivery of oncology led referrals to palliative care (PC) by examining physician attitudes and referral practices. Methods An online survey was circulated to oncologists and PC physicians in Ireland. Results The study (N = 100) comprised sixty-nine oncologists (69%) and thirty-one PC physicians (31%). Ninety-two(92%) believe patients with advanced cancer should receive concurrent treatment, however only 53% of oncologists(N = 37) routinely refer. Regarding end-of-life (EOL) care: 81% of oncologists (N = 55) are directly involved in its administration, despite 84% (N = 53) agreeing patients benefit when PC specialists coordinate EOL care. Conclusion The gulf between positive attitudes and limited implementation suggests the need for interdisciplinary changes to facilitate integration of PC in clinical practice in Ireland.

A regional analysis of epidermal growth factor receptor (EGFR) mutated lung cancer for HSE South.

BACKGROUND: EGFR mutated lung cancer represents a subgroup with distinct clinical presentations, prognosis, and management requirements. We investigated the survival, prognostic factors, and real-world treatment of NSCLC patients with EGFR mutation in clinical practice. METHODS: A retrospective review of all specimens sent for EGFR analysis from December 2009 to September 2015 was performed. Patient demographics, specimen type, EGFR mutation status/type, stage at diagnosis, treatment, response rate, and survival data were recorded. RESULTS: 27/334 (8%) patient specimens sent for EGFR testing tested positive for a sensitising EGFR mutation. The median age was 65 years (40-85 years). Exon 19 deletion represented the most commonly detected alteration, accounting for 39% (n = 11). First-line treatment for those with Exon 18, 19, or 21 alterations (n = 24) was with an EGFR tyrosine kinase inhibitor (TKI) in 79% (n = 19). Objective response rate among these patients was 74% and median duration of response was 13 months (range 7-35 months). CONCLUSION: The incidence of EGFR mutation in our cohort of NSCLC is 9% which is consistent with mutation incidence reported in other countries. The rate of EGFR mutation in our population is slightly below that reported internationally, but treatment outcomes are consistent with published data. Real-world patient data have important contributions to make with regard to quality measurement, incorporating patient experience into guidelines and identifying safety signals.

Vinorelbine induced perforation of a metastatic gastric lesion.

BACKGROUND: Breast carcinoma metastasis to the gastrointestinal tract is rare and more frequently associated with lobular than ductal carcinoma (Borst and Ingold, Surg 114(4):637-641 [1]). The purpose of this article is to present a case based review of a unique gastrointestinal metastasis and literature review. METHODS: A 46 year old lady with metastatic invasive ductal breast cancer was admitted to A&E with sudden onset of epigastric and left shoulder pain. She completed the first cycle of capecitabine/vinorelbine 1 week previously. Clinical examination revealed a tender epigastrium with rigidity in the upper abdomen. Free air under the diaphragm and a positive Rigler's sign was radiologically identified. A laparoscopy demonstrated a fibrinous exudate in the left upper quadrant consistent with a walled off lesser curvature gastric perforation. A subsequent oesophagogastroduodenoscopy (OGD) demonstrated a healed gastric ulcer of benign appearance; however the pathology confirmed metastatic breast carcinoma. RESULTS: Literature review confirmed no previously reported cases of vinorelbine induced gastric perforation. Four cases of metastatic breast cancer with gastric metastasis presenting with perforation were identified; three of these cases (Fra et al., Presse Med 25(26):1215 (1996) [2], Solis-Caxaj et al., Gastroenterol Clin Biol 28(1):91-92 (2004) [3], Ghosn et al., Bull Cancer 78(11):1071-1073 (1991) [4]), were in the French medical literature, including one male patient (Fra et al., Presse Med 25(26):1215 (1996) [2]) and at least one ductal breast carcinoma (Solis-Caxaj et al., Gastroenterol Clin Biol 28(1):91-92 (2004) [3]). The fourth case (van Geel et al., Ned Tijdschr Geneeskd 144(37):1761-1763 (2000) [5]), was in the Dutch medical literature and a lobular breast carcinoma. CONCLUSION: This case represents a rare complication of breast cancer chemotherapy, the subsequent significant benefit the patient received from treatment is consistent with the chemosensitivity to therapy that also resulted in gastric perforation. Five years after gastric perforation she resumed palliative chemotherapy after progression on sequential hormonal therapies.

GvHD after umbilical cord blood transplantation for acute leukemia: an analysis of risk factors and effect on outcomes.

Using the Center for International Blood and Marrow Transplant Research (CIBMTR) registry, we analyzed 1404 umbilical cord blood transplantation (UCBT) patients (single (<18 years)=810, double (⩾18 years)=594) with acute leukemia to define the incidence of acute GvHD (aGvHD) and chronic GvHD (cGvHD), analyze clinical risk factors and investigate outcomes. After single UCBT, 100-day incidence of grade II-IV aGvHD was 39% (95% confidence interval (CI), 36-43%), grade III-IV aGvHD was 18% (95% CI, 15-20%) and 1-year cGvHD was 27% (95% CI, 24-30%). After double UCBT, 100-day incidence of grade II-IV aGvHD was 45% (95% CI, 41-49%), grade III-IV aGvHD was 22% (95% CI, 19-26%) and 1-year cGvHD was 26% (95% CI, 22-29%). For single UCBT, multivariate analysis showed that absence of antithymocyte globulin (ATG) was associated with aGvHD, whereas prior aGvHD was associated with cGvHD. For double UCBT, absence of ATG and myeloablative conditioning were associated with aGvHD, whereas prior aGvHD predicted for cGvHD. Grade III-IV aGvHD led to worse survival, whereas cGvHD had no significant effect on disease-free or overall survival. GvHD is prevalent after UCBT with severe aGvHD leading to higher mortality. Future research in UCBT should prioritize prevention of GvHD.

Limited HLA sequence variation outside of antigen recognition domain exons of 360 10 of 10 matched unrelated hematopoietic stem cell transplant donor-recipient pairs.

Traditional DNA-based typing focuses primarily on interrogating the exons of human leukocyte antigen (HLA) genes that form the antigen recognition domain (ARD). The relevance of mismatching donor and recipient for HLA variation outside the ARD on hematopoietic stem cell transplantation (HSCT) outcomes is unknown. This study was designed to evaluate the frequency of variation outside the ARD in 10 of 10 (HLA-A, -B, -C, -DRB1, -DQB1) matched unrelated donor transplant pairs (n = 360). Next-generation DNA sequencing was used to characterize both HLA exons and introns for HLA-A, -B, -C alleles; exons 2, 3 and the intervening intron for HLA-DRB1 and exons only for HLA-DQA1 and -DQB1. Over 97% of alleles at each locus were matched for their nucleotide sequence outside of the ARD exons. Of the 4320 allele comparisons overall, only 17 allele pairs were mismatched for non-ARD exons, 41 for noncoding regions and 9 for ARD exons. The observed variation between donor and recipient usually involved a single nucleotide difference (88% of mismatches); 88% of the non-ARD exon variants impacted the amino acid sequence. The impact of amino acid sequence variation caused by substitutions in exons outside ARD regions in D-R pairs will be difficult to assess in HSCT outcome studies because these mismatches do not occur very frequently.

p19(Arf) is required for the cellular response to chronic DNA damage.

The p53 tumor suppressor is a stress sensor, driving cell cycle arrest or apoptosis in response to DNA damage or oncogenic signals. p53 activation by oncogenic signals relies on the p19(Arf) tumor suppressor, while p53 activation downstream of acute DNA damage is reported to be p19(Arf)-independent. Accordingly, p19(Arf)-deficient mouse embryo fibroblasts (MEFs) arrest in response to acute DNA damage. However, p19(Arf) is required for replicative senescence, a condition associated with an activated DNA damage response, as p19(Arf)-/- MEFs do not senesce after serial passage. A possible explanation for these seemingly disparate roles for p19(Arf) is that acute and chronic DNA damage responses are mechanistically distinct. Replicative senescence may result from chronic, low-dose DNA damage responses in which p19(Arf) has a specific role. We therefore examined the role of p19(Arf) in cellular responses to chronic, low-dose DNA-damaging agent treatment by maintaining MEFs in low oxygen and administering 0.5 G y γ-irradiation daily or 150 µM hydroxyurea, a replication stress inducer. In contrast to their response to acute DNA damage, p19(Arf)-/- MEFs exposed to chronic DNA damage do not senesce, revealing a selective role for p19(Arf) in senescence upon low-level, chronic DNA damage. We show further that p53 pathway activation in p19(Arf)-/- MEFs exposed to chronic DNA damage is attenuated relative to wild-type MEFs, suggesting a role for p19(Arf) in fine-tuning p53 activity. However, combined Nutlin3a and chronic DNA-damaging agent treatment is insufficient to promote senescence in p19(Arf)-/- MEFs, suggesting that the role of p19(Arf) in the chronic DNA damage response may be partially p53-independent. These data suggest the importance of p19(Arf) for the cellular response to the low-level DNA damage incurred in culture or upon oncogene expression, providing new insight into how p19(Arf) serves as a tumor suppressor. Moreover, our study helps reconcile reports suggesting crucial roles for both p19(Arf) and DNA damage-signaling pathways in tumor suppression.

Is there a role for the development of a supra-regional network for the management of penile cancer in the Republic of Ireland?

INTRODUCTION: There is an average of 25 cases of penile cancer in the Republic of Ireland each year. Due to the low volume of cases, the National Institute for Clinical Excellence recommends that treatment is centralised to allow the best standardised treatment for primary tumours and nodal disease. OBJECTIVES: To determine whether outcomes for patients with penile cancer differed significantly between secondary and tertiary referral centres in the Republic of Ireland. METHODS: Between 2001 and 2014, 36 patients were treated in the Mercy University Hospital (MUH) with penile cancer. Twenty patients were treated primarily in MUH and 16 patients underwent initial management in a secondary referral centre (SRC) with subsequent referral to the MUH. A retrospective matched case-control study was performed on this patient cohort. RESULTS: There were no significant differences in length of follow-up or risk factors for the development of penile cancer between both groups (p = 0.6 and p = 0.5 respectively) Ultimately, the incidence of high risk disease, nodal metasases, high grade disease and pelvic lymph node dissection were significantly greater in patients that were initially managed in a SRC (p = 0.02, p = 0.03, p = 0.004 and p = 0.028 respectively). Patients undergoing initial treatment in a SRC had a non-significantly reduced rate of cancer specific survival (88 Vs 66%, MUH Vs SRCs, p = 0.495) and recurrence free survival (85 Vs 46%, MUH Vs SRCs, p = 0.24). CONCLUSION: Our findings suggest that managing penile cancer in special interest centres may improve oncological outcome.

Six-core versus twelve-core prostate biopsy: a retrospective study comparing accuracy, oncological outcomes and safety.

AIMS: To compare sextant and 12 core transrectal ultrasound-guided (TRUS) prostate biopsies for detecting prostate cancer (PCa) and to determine whether 12-core prostate biopsies are associated with a higher incidence of insignificant prostate cancer and complications. METHODS: A retrospective study was performed on all patients with a positive TRUS biopsy for prostate cancer between January 2011 and December 2013. Group A underwent a sextant core prostate biopsy and group B underwent a 12-core prostate biopsy. Outcome variables were cancer detection rates, oncological outcomes, incidence of clinically insignificant PCa and incidence of biopsy associated complications. Exclusion criteria included a negative TRUS biopsy and metastatic prostate cancer. RESULT: In total 718 prostate biopsies were performed and 286 patients met inclusion criteria (143 patients in each group). The overall cancer detection rate was 43 % in group A compared to 53 % in group B (p = 0.03). In group A, 31 (21.7 %) patients proceeded to open retropubic radical prostatectomy (RRP) compared to 36 (25.2 %) in group B (p = 0.7). Sextant biopsies were associated with a significantly higher rate of upgrading compared to 12-core biopsies in RRP specimens (51.6 versus 25 % respectively, p < 0.01). The incidence of clinically insignificant PCa was 10.5 % in group A versus 14.7 % in group B (p = 0.2). The incidence of urosepsis post biopsy was 0.7 % in both groups (n = 1). CONCLUSION: Twelve-core biopsies were associated with higher PCa cancer detection rates, greater accuracy for Gleason grading and no differences for detecting clinically insignificant PCa or urosepsis compared to sextant biopsies.

A novel rapid access testicular cancer clinic: prospective evaluation after one year.

BACKGROUND: Our institution has recently developed a rapid access outpatient clinic to investigate men with testicular lumps and/or pain suspicious for testicular cancer (TCa). AIMS: To present our experience after 12 months. METHODS: All referrals to the rapid access testicular clinic (RATC) clinic were prospectively analysed from 01/01/2013 to 01/01/2014. The primary outcome variable was incidence of TCa in the referred patient cohort. Secondary outcome variables were waiting times prior to clinical review and waiting times prior to radical orchidectomy in patients diagnosed with TCa. RESULTS: Seventy-four new patients were referred to the RATC during the 1-year period and the mean age was 34 (range 15-81 years). TCa was the most common diagnosis and was found in 18 (25 %) patients. Patients diagnosed with TCa underwent radical orchidectomy, a median of 3 (range 1-5) days after their initial GP referral. Patients requiring surgical intervention for benign scrotal pathology underwent their procedure a median of 32 (range 3-61) days after their initial referral. Of the 18 patients diagnosed with TCa, 9 (50 %) were diagnosed with a seminomatous germ cell tumour on histopathology. CONCLUSION: The RATC is a new initiative in Ireland that provides expedient and definitive treatment of patients with newly diagnosed TCa. Early treatment will ultimately improve long-term prognosis in this patient cohort.

Interstitial cystitis/painful bladder syndrome: epidemiology, pathophysiology and evidence-based treatment options.

Interstitial cystitis/painful bladder syndrome (IC/PBS) is a chronic debilitating condition that can have a severely negative impact on a patient's quality of life. Its prevalence ranges from 52 to 500/100,000 in females compared to 8-41/100,000 in males, and its incidence is increasing globally. Treatment algorithms are sub-classified into behavioural, pharmacological, intravesical, interventional and surgical therapies. Short-term (i.e. <1 year) cure rates range from 50% to 75% for non-/minimally-invasive therapies, but repeat administration of a therapeutic agent is required. Although definitive surgical intervention is associated with greater long-term cure rates (≥80%); significant short- and long-term adverse effects occur more frequently. Clinicians are likely to experience increasing numbers of patients with IC/PBS as more is understood about its pathophysiology and evolving epidemiology. Therefore urogynaecologists should familiarise themselves with appropriate diagnostic criteria and evidence based therapies to optimise clinical outcomes in this patient cohort.

Trends and attitudes towards paediatric circumcision in the South of Ireland.

BACKGROUND: Paediatric circumcision is one of the oldest surgical procedures performed worldwide. Traditionally performed by general surgeons, paediatric surgeons and urologists, there is a falling trend in the rate of paediatric circumcision being performed by adult and paediatric general surgeons. There is currently no corresponding contemporary data pertaining to trends and attitudes of general surgeons to paediatric circumcision in Ireland. AIM: The aim of this study was to assess the trends and attitudes of consultant general surgeons, and to assess its potential impact on the specialist delivery of paediatric urological care. METHODS: A questionnaire was mailed to all practicing general surgeons in whom we identified as having a potential role in the management of paediatric circumcision. Data pertaining to population demographics within the south of Ireland were accessed through the Central Statistics Office. RESULTS: There was an 89 % response rate to the questionnaire survey. Seventy-seven percent of those under 50 were trained in adult circumcision compared with 100 % of those respondents over 50 years. There was a significant difference in paediatric circumcision with only 24 % those under 50 performing this procedure compared with 68 % above 50 years. Eighty-six percent respondents under 45 years (35 % over 45 years) felt that this procedure should be carried out by urology. CONCLUSION: In a region with an expanding paediatric population, it is crucial to maintain paediatric urological services. Given present trends and attitudes of newer appointed general surgeons, it is essential that further specialist appointments are made, and funding directed towards demand in order to keep pace.

Inducing apoptosis of cancer cells using small-molecule plant compounds that bind to GRP78.

BACKGROUND: Glucose regulated protein 78 (GRP78) functions as a sensor of endoplasmic reticulum (ER) stress. The aim of this study was to test the hypothesis that molecules that bind to GRP78 induce the unfolded protein response (UPR) and enhance cell death in combination with ER stress inducers. METHODS: Differential scanning calorimetry (DSC), measurement of cell death by flow cytometry and the induction of ER stress markers using western blotting. RESULTS: Epigallocatechin gallate (EGCG), a flavonoid component of Green Tea Camellia sinensis, and honokiol (HNK), a Magnolia grandiflora derivative, bind to unfolded conformations of the GRP78 ATPase domain. Epigallocatechin gallate and HNK induced death in six neuroectodermal tumour cell lines tested. Levels of death to HNK were twice that for EGCG; half-maximal effective doses were similar but EGCG sensitivity varied more widely between cell types. Honokiol induced ER stress and UPR as predicted from its ability to interact with GRP78, but EGCG was less effective. With respect to cell death, HNK had synergistic effects on melanoma and glioblastoma cells with the ER stress inducers fenretinide or bortezomib, but only additive (fenretinide) or inhibitory (bortezomib) effects on neuroblastoma cells. CONCLUSION: Honokiol induces apoptosis due to ER stress from an interaction with GRP78. The data are consistent with DSC results that suggest that HNK binds to GRP78 more effectively than EGCG. Therefore, HNK may warrant development as an antitumour drug.

Surgical specialty procedures in rural surgery practices: implications for rural surgery training.

BACKGROUND: Specialty procedures constitute one eighth of rural surgery practice. Currently, general surgeons intending to practice in rural hospitals may not get adequate training for specialty procedures, which they will be expected to perform. Better definition of these procedures will help guide rural surgery training. METHODS: Current Procedural Terminology codes for all surgical procedures for 81% of North Dakota and South Dakota rural surgeons were entered into the Dakota Database for Rural Surgery. Specialty procedures were analyzed and compared with the Surgical Council on Resident Education curriculum to determine whether general surgery training is adequate preparation for rural surgery practice. RESULTS: The Dakota Database for Rural Surgery included 46,052 procedures, of which 5,666 (12.3%) were specialty procedures. Highest volume specialty categories included vascular, obstetrics and gynecology, orthopedics, cardiothoracic, urology, and otolaryngology. Common procedures in cardiothoracic and vascular surgery are taught in general surgical residency, while common procedures in obstetrics and gynecology, orthopedics, urology, and otolaryngology are usually not taught in general surgery training. CONCLUSIONS: Optimal training for rural surgery practice should include experience in specialty procedures in obstetrics and gynecology, orthopedics, urology, and otolaryngology.

Laser absorption in relativistically underdense plasmas by synchrotron radiation.

A novel absorption mechanism for linearly polarized lasers propagating in relativistically underdense solids in the ultrarelativistic (a ~ 100) regime is presented. The mechanism is based on strong synchrotron emission from electrons reinjected into the laser by the space charge field they generate at the front of the laser pulse. This laser absorption, termed reinjected electron synchrotron emission, is due to a coupling of conventional plasma physics processes to quantum electrodynamic processes in low density solids at intensities above 10(22) W/cm(2). Reinjected electron synchrotron emission is identified in 2D QED-particle-in-cell simulations and then explained in terms of 1D QED-particle-in-cell simulations and simple analytical theory. It is found that between 1% (at 10(22) W/cm(2)) and 14% (at 8 × 10(23) W/cm(2)) of the laser energy is converted into gamma ray photons, potentially providing an ultraintense future gamma ray source.