Endocrinology: Two cases of ovarian tumours in women who had undergone multiple ovarian stimulation attempts

Concerns have been raised recently about the possible associationbetween superovulation and ovarian cancer. In order to contributeto the limited literature on this important issue, two casesof ovarian tumours in women who had undergone multiple ovulationinductions are presented. In the first case, the patient hadsecondary anovulatory infertility. She was treated with humanmenopausal gonadotrophin (HMG) alone and in combination withclomiphene citrate or buserelin for six cycles. She then underwentovarian stimulation with buserelin/HMG in the long protocolfor in-vitro fertilization (IVF) and embryo transfer. In preparationfor a new IVF/embryo transfer attempt, 8 months later, the screeningultrasound revealed a cystic formation of the left ovary andan enlargement of the right. During laparotomy, both ovarieswere found to bear large tumours (approximately 6x5x4 cm) whichwere removed. Histological examination showed that they wereepithelial tumours (serous-papillary cystadenomas) of borderlinemalignancy. The patient conceived spontaneously 1.5 years afterthe operation. In the second case, the patient presented withsecondary anovulatory infertility. She underwent ovulation inductionwith clomiphene/HMG and with buserelin/HMG in the long protocol,and intra-uterine insemination with husband's spermatozoa andconceived (singleton pregnancy). She was delivered by Caesareansection, during which a cystic tumour of the left ovary wasremoved. Histological examination revealed a benign mucous cystadenomaof the ovary. In conclusion, the clinical information from thesetwo cases does not support a causal association between ovarianstimulation and ovarian tumours but does potntially supporta facilitating one.     

Selective transperineal prostate biopsy for fluoroquinolone-resistance patients reduces sepsis and cost

Background:Urosepsis is a recognized complication of transrectal ultrasound-guided prostate biopsy (TRUS-Bx). Pre-biopsy rectal swabs have been used to identify patients with microorganisms in the rectal flora resistant to the conventionally used empirical prophylaxis. The transperineal route of biopsy (TP-Bx) has a lower complication risk but comes at an increased cost.Materials and methods:Retrospective cohort study including patients undergoing prostate biopsies between October/2015 and April/2018. The intervention cohort, a rectal swab was performed, the result of which dictated the biopsy route; TRUS-Bx against TP-Bx. TP-Bx for patients with fluoroquinolone resistance or extended-spectrum β-lactamase. The control cohort underwent TRUS without a rectal swab receiving empirical antibiotics—oral ciprofloxacin and intravenous gentamicin.Results:Total 1000 patients were included in which 500 underwent a swab, 14 (2.8%) developed post-TRUS biopsy infective complications with 3 having positive bacteremia (0.6%); 500 had no swab, 47 (9.4%) developed post-TRUS biopsy infective complications with 22 (4.4%, p < 0.05) having positive bacteremia. Three patients (0.6%) of patients who underwent swab developed urinary tract infection symptoms whilst 12 (2.4%) had urinary tract infection in the control group. In those patients that underwent a swab, 14 required hospitalization with mean length of stay of 2.5 days versus 43 patients of the control with 3.6 days. Cost analysis concluded savings of this strategy was £18,711.Conclusions:We have demonstrated a protocol that reserves template biopsies for higher risk patients and can significantly reduce sepsis and other infectious complication rates whilst also proving to be a cost-efficient strategy. We recommend that units not utilizing rectal swabs to uncover the fluoroquinolone resistance rate by introducing them. We advocate units that already utilize rectal swabs, to introduce transperineal biopsy for their higher risk patients.     

Regression of endometrial hyperplasia after treatment with the gonadotrophin-releasing hormone analogue triptorelin: a prospective study

Endometrial hyperplasia is thought to be caused by the prolonged, unopposed oestrogenic stimulation of the endometrium. The regression of hyperplastic back to normal endometrium is the main purpose of any conservative treatment in order to prevent development of adenocarcinoma. The aim of this study was to evaluate the regression of hyperplastic to normal endometrium in patients with various forms of endometrial hyperplasia after treatment with the gonadotrophin-releasing hormone analogue (GnRHa) triptorelin for 6 months. Fifty-six patients with endometrial hyperplasia were enrolled in this trial; 39 patients (group I) presented simple hyperplasia, 14 (group II) complex hyperplasia and three (group III) atypical complex hyperplasia. All patients were treated with triptorelin for 6 months. Bleeding control during treatment was excellent. A post-treatment curettage for estimation of endometrial histology was performed on 54 out of 56 patients 100.1 +/- 44.7 days after the last triptorelin dose, following the restoration of pituitary function. Regression of hyperplastic to normal endometrium was observed in 32 (86.5%) out of 37 patients in group I and in 12 (85.7%) out of 14 in group II. Persistence of simple hyperplasia was found in five (14.5%) out of 37 patients in group I. Persistence of complex hyperplasia was found in 1 (7.1%) out of 14 patients and progression to atypical complex hyperplasia in another one (7.1%) woman in group II. In some of these cases, the presence of risk factors such as obesity, diabetes mellitus and ovulatory disturbances may contribute to the disease persistence despite therapy. On the other hand, in group III, none of the three patients had normal post-treatment endometrial histology. It seems, therefore, that in cases of endometrial hyperplasia without atypia, the administration of the GnRHa triptorelin is associated with high regression rates to normal endometrium. Conversely, the presence of atypia seems to be a poor prognostic factor. Treatment tolerance and bleeding control during therapy is excellent.     

Sleep and Sleep-Wake Disturbances in Care Recipient-Caregiver Dyads in the Context of a Chronic Illness: A Critical Review of the Literature

ContextAlterations in sleep-wake patterns of care recipients and their informal caregivers are common in the context of a chronic illness. Given the current notion that sleep may be regulated within and affected by close human relationships, concurrent and interrelated sleep problems may be present in care recipient-caregiver dyads.ObjectivesTo critically analyze evidence regarding concurrent sleep patterns or changes in care recipient-caregiver dyads in the context of a chronic illness and address methodological and research gaps.MethodsUsing a wide range of key terms and synonyms, three electronic databases (Medline, CINAHL, and Embase) were systematically searched for the period between January 1990 and July 2011.ResultsTen studies met prespecified selection criteria and were included for analysis. Study quality was fair to good on average. Seven studies were conducted in the context of dementia or Parkinson's disease, two in the context of cancer, and one study included a group of community elders with mixed related comorbidities and their informal caregivers. Bidirectional associations in the sleep of care recipient-caregiver dyads seem to exist. Concurrent and comparable nocturnal sleep disruptions also may be evident. Yet, inconsistencies in the methods implemented, and the samples included, as well as uncertainty regarding factors coaffecting sleep, still preclude safe conclusions to be drawn on.ConclusionThe dyadic investigation of sleep is a promising approach to the development of truly effective interventions to improve sleep quality of care recipients and their caregivers. Nevertheless, more systematic, longitudinal dyadic research is warranted to augment our understanding of co-occurrence and over time changes of sleep problems in care recipient-caregiver dyads, as well as to clarify covariates/factors that appear to contribute to these problems within the dyad and across time and context of illness.     

High‐frequency p16INK4A promoter methylation is associated with histone methyltransferase SETDB1 expression in sporadic cutaneous melanoma

Epigenetic mechanisms participate in melanoma development and progression. The effect of histone modifications and their catalysing enzymes over euchromatic promoter DNA methylation in melanoma remains unclear. This study investigated the potential association of p16^INK4A promoter methylation with histone methyltransferase SETDB1 expression in Greek patients with sporadic melanoma and their correlation with clinicopathological characteristics. Promoter methylation was detected by methylation‐specific PCR in 100 peripheral blood samples and 58 melanoma tissues from the same patients. Cell proliferation (Ki‐67 index), p16^INK4A and SETDB1 expression were evaluated by immunohistochemistry. High‐frequency promoter methylation (25.86%) was observed in tissue samples and correlated with increased cell proliferation (P = 0.0514). p16^INK4A promoter methylation was higher in vertical growth‐phase (60%) melanomas than in radial (40%, P = 0.063) and those displaying epidermal involvement (P = 0.046). Importantly, p16^INK4A methylation correlated with increased melanoma thickness according to Breslow index (P = 0.0495) and marginally with increased Clark level (I/II vs III/IV/V, P = 0.070). Low (1–30%) p16^INK4A expression was detected at the majority (19 of 54) of melanoma cases (35.19%), being marginally correlated with tumor lymphocytic infiltration (P = 0.078). SETDB1 nuclear immunoreactivity was observed in 47 of 57 (82.46%) cases, whereas 27 of 57 (47.37%) showed cytoplasmic immunoexpression. Cytoplasmic SETDB1 expression correlated with higher frequency of p16^INK4A methylation and p16^INK4A expression (P = 0.033, P = 0.011, respectively). Increased nuclear SETDB1 levels were associated with higher mitotic count (0–5/mm² vs >5/mm², P = 0.0869), advanced Clark level (III‐V, P = 0.0380), epidermal involvement (P = 0.0331) and the non‐chronic sun exposure‐associated melanoma type (P = 0.0664). Our data demonstrate for the first time the association of histone methyltransferase SETDB1 with frequent methylation of the euchromatic p16^INK4A promoter and several prognostic parameters in melanomas.     

Outbreak Caused by an Ertapenem-Resistant,CTX-M-15-Producing Klebsiella pneumoniae Sequence Type 101 Clone Carrying an OmpK36 Porin Variant

Although numerous studies have documented outbreaks of carbapenem-resistant Klebsiella pneumoniae (CRKP) possessing various carbapenemases, reports on outbreaks due to CRKP possessing extended-spectrum β-lactamases (ESBLs) and/or AmpCs with porin lesions have been limited. Here, we describe an outbreak caused by an ertapenem-resistant, CTX-M-15-producing clonal K. pneumoniae strain expressing an OmpK36 porin variant. From May 2012 to November 2012, 37 ertapenem-resistant K. pneumoniae isolates phenotypically negative for carbapenemase production were recovered from 19 patients hospitalized in the intensive care unit of a Greek hospital. The isolates were either susceptible or intermediate to other carbapenems and resistant to all remaining β-lactams but cefotetan. Phenotypic and molecular analysis revealed the presence in all isolates of the bla_CTX-M-15 gene on a conjugative 100-kb plasmid, disruption in the expression of the ompK35 gene, and the production of an Ompk36 porin variant. The index case was a patient admitted from another hospital. Active surveillance upon admission and on a weekly basis was immediately initiated; environmental samples were also periodically tested. Molecular typing showed that all clinical isolates as well as two ertapenem-resistant environmental K. pneumoniae isolates belonged to the same clonal type and were assigned to multilocus sequence typing (MLST) sequence type 101 (ST101). As all colonized/infected patients were hospitalized during overlapping periods, cross-infection was considered the main route for the dissemination of the outbreak strain. Despite reinforcement of infection control measures and active surveillance, the outbreak lasted approximately 7 months. Identification of hidden carriers upon admission and by screening on a weekly basis was found valuable for early recognition and subsequent successful management of the outbreak.     

How much do PPIs contribute to C. difficile infections?

Two separate systematic reviews and meta-analyses published in this edition of the American Journal of Gastroenterology conclude that proton pump inhibitor (PPI) use is associated with an ~70% increase in the risk of Clostridium difficile infection (CDI). The two reviews employed different methodology but reached very similar conclusions. However, since the quality of evidence from the individual studies that were included in these analyses is relatively weak, their conclusions must be interpreted cautiously. Observational studies--and even well-conducted systematic reviews of observational studies--rarely provide adequate evidence to prove causality rather than mere association. However, given both the widespread use of PPIs and the increasing incidence and importance of CDI, it is important that this association is adequately explored.     

Eosinophilic responses to stent implantation and the risk of Kounis hypersensitivity associated coronary syndrome

The use of drug eluting stents constitutes a major breakthrough in current interventional cardiology because it is more than halves the need of repeat interventions. It is incontrovertible that coronary stents, in general, have been beneficial for the vast majority of patients. A small increase in thrombosis, following DES implantation, is offset by a diminished risk of complications associated with repeat vascularization. However, late and, especially, very late stent thrombosis is a much feared complication because it is associated with myocardial infarction with increased mortality. Despite that stent thrombosis is thought to be multifactorial, so far clinical reports and reported pathology findings in patients died from coronary stent thrombosis as well as animal studies and experiments, point toward a hypersensitivity inflammation. The stented and thrombotic areas are infiltrated by interacting, via bidirectional stimuli inflammatory cells including eosinophils, macrophages, T-cells and mast cells. Stented regions constitute an ideal surrounding for endothelial damage and dysfunction, together with hemorheologic changes and turbulence as well as platelet dysfunction, coagulation and fibrinolytic disturbances. Drug eluting stent components include the metal strut which contains nickel, chromium, manganese, titanium, molybdenum, the polymer coating and the impregnated drugs which for the first generation stents are: the antimicrotubule antineoplastic agent paclitaxel and the anti-inflammatory, immunosuppressive and antiproliferative agent sirolimus. The newer stents which are called cobalt-chromiun stents and elute the sirolimus analogs everolimus and zotarolimus both contain nickel and other metals. All these components constitute an antigenic complex inside the coronary arteries which apply chronic, continuous, repetitive and persistent inflammatory action capable to induced Kounis syndrome and stent thrombosis. Allergic inflammation goes through three phases, the early phase, the late phase and the chronic phase and these three phases correspond temporally with early (acute and sub acute), late and very late stent thrombosis. Bioabsorbable allergy free poly lactic acid self expanding stents, nickel free stainless steel materials, stent coverage with nitric oxide donors and antibodies with endothelial progenitor cell capturing abilities as well as stents eluting anti-inflammatory and anti-allergic agents might be the solution of this so feared and devastating stent complication.