Umbilical Endometriosis Disguised by Seborrheic Keratosis on Punch Biopsy.

ABSTRACT: Endometriosis is a benign condition of the female genital system, characterized by endometrial tissue external to the uterine cavity. Of all cases with endometriosis, the incidence of umbilical endometriosis is only 0.29%. Umbilical endometriosis typical presents with symptoms including cyclical pain, bleeding, and swelling of the nodule. Morphological changes in the epidermis, as in this case, simulating a seborrheic keratosis both clinically and microscopically, can initially mask the underlying endometriosis and prolong the course of treatment. A thorough anamnesis and examination revealing the characteristic symptoms and findings coupled with a representative biopsy is essential to correctly diagnose umbilical endometriosis.

Five-Year Outcome of MiniArc Single-Incision Sling Used in the Treatment of Primary Urodynamic Stress Incontinence.

STUDY OBJECTIVE: To evaluate the effectiveness and safety of the MiniArc single-incision sling in the treatment of urodynamic stress incontinence (USI) through 5 years. DESIGN: Retrospective observational study (Canadian Task Force classification II-2). SETTING: Tertiary referral center. PATIENTS: Eighty-five patients with USI without needing concurrent procedures who underwent anti-incontinence surgery using the MiniArc SIMS from February 2010 to December 2011. INTERVENTIONS: Anti-incontinence surgery. MEASUREMENTS AND MAIN RESULTS: Objective cure was defined as no demonstrable leakage of urine on the cough stress test and 1-hour pad test weight <2 g. Subjective cure was based on negative response to Urinary Distress Inventory question 3, no leakage on coughing, sneezing, or laughing. Most patients were postmenopausal, overweight, and multiparous. Postoperative USI significantly improved (p < .001) through 3 years, and the 1-hour pad test showed significant improvement through 5 years (p < .001). Although 13 patients had recurrence of USI, no repeat surgery was done. The cumulative cure rates may show a declining trend of cure, yet subjective cure was 80.0% and objective cure 84.7%, with age as a significant risk factor for sling failure. CONCLUSION: MiniArc maintains its effectiveness and safety in treatment of USI through 5 years with high objective and subjective cure rates and low incidence of complications.

Predictors of voiding dysfunction following extensive vaginal pelvic reconstructive surgery.

INTRODUCTION AND HYPOTHESIS: The objective of this study was to identify the predictors of postoperative voiding dysfunction in women following extensive vaginal pelvic reconstructive surgery. METHODS: We enrolled 1,425 women who had pelvic organ prolapse of POP-Q stage III or IV and had undergone vaginal pelvic reconstructive surgery with or without transvaginal mesh insertion from January 2006 to December 2014. All subjects were required to complete a 72-h voiding diary, and the IIQ-7, UDI-6, POPDI-6 and PISQ-12 questionnaires. Urodynamic study was performed preoperatively and postoperatively. RESULTS: Of the 1,425 women, 54 were excluded due to incomplete data, and 1,017 of the remaining 1,371 (74.2 %) had transvaginal mesh surgery and 247 (18 %) had concurrent midurethral sling insertion. Of 380 women (27.7 %) with preoperative voiding dysfunction, 37 (9.7 %) continued to have voiding dysfunction postoperatively. Of the remaining 991 women (72.3 %) with normal preoperative voiding function, 11 (1.1 %) developed de novo voiding dysfunction postoperatively. The overall incidence of postoperative voiding dysfunction was 3.5 % (48/1,371). Those with concurrent midurethral sling insertion were at higher risk of developing voiding dysfunction postoperatively (OR 3.12, 95 % CI 1.79 - 5.46, p < 0.001). Diabetes mellitus, preoperative detrusor pressure at maximal flow (Dmax) <10 cm H2O and postvoid residual volume ≥200 ml were significant risk factors for the development of postoperative voiding dysfunction (OR 3.07, 1.84 and 2.15, respectively; 95 % CI 1.69 - 5.60, 1.39 - 2.91 and 1.10 - 3.21, respectively). CONCLUSIONS: Diabetes mellitus, concurrent midurethral sling insertion, preoperative Dmax <10 cm H2O and postvoid residual volume ≥200 ml in patients with advanced pelvic organ prolapse were risk factors for the development of postoperative voiding dysfunction after vaginal pelvic reconstructive surgery. Therefore, counseling is worthwhile before considering vaginal pelvic reconstructive surgery.

Transvaginal management of severe pelvic organ prolapse in nulliparous women.

AIM: The aim of this study was to evaluate the management outcomes of advanced pelvic organ prolapse (POP) in nulliparous women. METHODS: Eight nulliparous women diagnosed with POP ≥ stage 3 between January 2005 and August 2013, according to the Pelvic Organ Quantification System (POPQ), were reviewed. Seven were managed surgically and one was managed with pessary. Primary outcome was surgical objective cure (POP-Q ≤ 1) and subjective cure, defined as negative response to questions 2 and 3 on Pelvic Organ Prolapse Distress Inventory 6. Secondary outcomes were complications, symptoms' severity and quality of life according to validated questionnaires. RESULTS: A total of 1275 prolapse patients with POP-Q ≥ stage 3 were managed surgically, among whom seven (0.55%) were nulliparous. Each woman had at least one risk factor associated with POP. Risk factors identified were history of pelvic trauma, obesity, menopause, chronic cough, hard physical labor and constipation. Five patients underwent surgical correction (vaginal hysterectomy with sacrospinous fixation) with mesh (Perigee, n = 3; Avaulta, n = 2). Two patients had uterine preservation without mesh (hysteropexy with sacrospinous ligament fixation). One patient preferred treatment with pessary. The total cure rate (objective and subjective cure rates) was 86% after surgical reconstructive surgery. CONCLUSION: Management of nulliparous advanced POP poses significant challenges with regard to uterine preservation, future pregnancy and childbirth. Conservative management with pessary insertion should be offered followed by surgical correction. Reconstructive surgery with mesh may improve prolapse symptoms objectively and subjectively.

Pre-immature dendritic cells (PIDC) pulsed with HPV16 E6 or E7 peptide are capable of eliciting specific immune response in patients with advanced cervical cancer.

BACKGROUND: The protein products of the early genes E6 and E7 in high-risk HPV types 16 and 18 have been implicated in the oncogenic capability of these viruses. Therefore, these peptides represent attractive vaccine therapy targets. METHODS: Thirty-two patients with advanced cervical cancer (HPV16 or 18 positive) were treated with HPV16 E6 (18-26) (Arm A) or HPV16 E7 (12-20) peptide (Arm B) pulsed on PBMCs in order to illicit immune response against the relevant peptide on both arms. These PBMCs were cultured for a short time (48 hours only) and in the presence of GM- CSF, accordingly, they were identified as "Pre-Immature Dentritic Cells". RESULTS: 51Cr release assay and ELISPOT demonstrated evidence of specific immune response against the relevant peptide in 10/16 (63%) evaluable patients in arm A and 7/12 (58%) in arm B. HPV16 E6 was found to be homologous to HPV18 E6 in both vivo and vitro. The median overall survival (OS) and progression free survival (PFS) for the full cohort was 10.0 and 3.5 months, respectively. There were no RECIST responses in any patient. The majority of toxicities were grade I and II. CONCLUSIONS: We demonstrated the feasibility and ability of Pre-Immature Dentritic Cells pulsed with HPV16 E6 (18-26) or HPV16 E7 (12-20) to induce a specific immune response against the relevant peptide despite the advanced disease of the cervical cancer patients treated on this trial. We believe that this observation deserves further investigations.

Medications and therapeutic apheresis procedures: are we doing our best?

Therapeutic apheresis refers to a group of extracorporeal therapies commonly used in the treatment of a variety of neurological, renal, hematological, and other systemic diseases caused by circulating "toxic agents" that cannot be cleared by other means. This article presents an overview of the concepts underlying the effect of therapeutic apheresis procedures on prescription drugs taken by patients and describes key drug-related and procedure-related factors that may impact drug disposition during therapeutic apheresis. Therapeutic apheresis, and specifically therapeutic plasma exchange (TPE), is the process involving the extracorporeal separation of plasma from the cellular components of blood, discarding the plasma and exchanging it with replacement physiologic fluids such as albumin or fresh frozen plasma to maintain oncotic pressure and blood volume, and then returning this and the original cellular components of blood back to the patient's circulatory system (Ibrahim and Balogun, Semin Dial 2012;25:176-189). Over the last 4 decades, modern therapeutic apheresis has been used clinically for the treatment of a host of renal, hematological, and neurological diseases such as Goodpasture's syndrome, thrombotic thrombocytopenic purpura, and myasthenia gravis to name a few (Ibrahim et al., Pharmacotherapy 2007;27:1529-1549). Because of its ability to remove plasma, TPE can extract circulating drugs residing in this compartment, thereby affecting their disposition and potentially their therapeutic action (Ibrahim and Balogun, Semin Dial 2012;25:176-189; Ibrahim et al., Pharmacotherapy 2007;27:1529-1549; Kale-Pradhan and Woo, Pharmacotherapy 1997;17:684-695; Kintzel et al., J Clin Apher 2003;18:194-205). The aim of this article is to shed light on drug-related and TPE-related factors that may influence drug removal by TPE. Emphasis is put on areas needing improvement in the way of assessing drug removal by TPE. In addition, a call for an expanded investigation of TPEs influence on select compounds is enlisted.

Establishment of a birth-to-education cohort of 1 million Palestinian refugees using electronic medical records and electronic education records.

Introduction: By linking datasets, electronic records can be used to build large birth-cohorts, enabling researchers to cost-effectively answer questions relevant to populations over the life-course. Currently, around 5.8 million Palestinian refugees live in five settings: Jordan, Lebanon, Syria, West Bank, and Gaza Strip. The United Nations Relief and Works Agency for Palestine Refugees in the Near East (UNRWA) provides them with free primary health and elementary-school services. It maintains electronic records to do so.We aimed to establish a birth cohort of Palestinian refugees born between 1st January 2010 and 31st December 2020 living in five settings by linking mother obstetric records with child health and education records and to describe some of the cohort characteristics. In future, we plan to assess effects of size-at-birth on growth, health and educational attainment, among other questions. Methods: We extracted all available data from 140 health centres and 702 schools across five settings, i.e. all UNRWA service users. Creating the cohort involved examining IDs and other data, preparing data, de-duplicating records, and identifying live-births, linking the mothers' and children's data using different deterministic linking algorithms, and understanding reasons for non-linkage. Results: We established a birth cohort of Palestinian refugees using electronic records of 972,743 live births. We found high levels of linkage to health records overall (83%), which improved over time (from 73% to 86%), and variations in linkage rates by setting: these averaged 93% in Gaza, 89% in Lebanon, 75% in Jordan, 73% in West Bank and 68% in Syria. Of the 423,580 children age-eligible to go to school, 47% went to UNRWA schools and comprised of 197,479 children with both health and education records, and 2,447 children with only education records. In addition to year and setting, other factors associated with non-linkage included mortality and having a non-refugee mother. Misclassification errors were minimal. Conclusion: This linked open birth-cohort is unique for refugees and the Arab region and forms the basis for many future studies, including to elucidate pathways for improved health and education in this vulnerable, understudied population. Our characterization of the cohort leads us to recommend using different sub-sets of the cohort depending on the research question and analytic purposes.

Medications in patients treated with therapeutic plasma exchange: prescription dosage, timing, and drug overdose.

Therapeutic plasma exchange (TPE) is an extracorporeal process commonly used in clinical medicine for the treatment of a variety of neurological, renal, hematological, dermatological, and other diseases. Inherent to the procedure, patients' plasma removal may lead to the extraction of drugs they are concurrently receiving. This review discusses the published literature assessing TPE's influence on different drug classes' disposition and, when applicable, sets forth management recommendations in cases where the drugs are used at the usual doses and in cases of drug overdose.

[Conservative treatment of iatrogenic milk fistula].

A milk fistula is a rare condition, and only 27 cases have been reported in the latest systematic review from 2020. A fistula can be iatrogenic or spontaneous. The content of tissue factors in breast milk promotes granulation in wounds, which can lead to hypergranulation and lack of epithelialization. In this case report, a 29-year-old breastfeeding woman developed a milk fistula after surgical removal of a naevus on suspicion of being a melanoma. Hypergranulation of the wound was successfully treated with corticosteroid, which inhibits growth factor in breastmilk, and breastfeeding was continued during treatment.

Dapsone-induced methemoglobinemia: a primer for clinicians.

OBJECTIVE: To present a comprehensive review of dapsone-induced methemoglobinemia and its management. DATA SOURCES: Literature retrieval was accessed through MEDLINE (1966-March 2011), Cochrane Library, and EMBASE, using the terms dapsone and methemoglobinemia. STUDY SELECTION AND DATA EXTRACTION: All case reports, small case series, and randomized controlled trials published in English were evaluated. Because of the absence of comprehensive updates on this topic since 1996, publications between 1997 and March 2011 were included in this review. DATA SYNTHESIS: Between 1997 and March 2011, the majority of publications describing methemoglobinemia associated with dapsone use reported this adverse effect at therapeutic doses. Excluding overdose situations, 18 described symptomatic dapsone-associated methemoglobinemia and clinical presentation ranging from cyanosis to dyspnea. In almost all of the accounts, patients had a concurrent event such as anemia or pneumonia, suggesting an interplay between these comorbidities and the onset of symptomatic methemoglobinemia. Delayed hemolytic anemia was seen in patients with high methemoglobin levels at presentation. Management in most cases consisted of administration of methylene blue. Overall, most reports described a successful outcome, and no mortality resulted from methemoglobinemia associated with therapeutic use. CONCLUSIONS: Clinicians should recognize methemoglobinemia as an adverse effect associated with dapsone use and the potential factors that precipitate it. They should also know how to promptly and effectively manage this event.

Posterior reversible encephalopathy syndrome in a patient with Richter's syndrome on combination DA-R-EPOCH chemotherapy regimen: a case report.

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is a clinical-radiologic entity characterized by headaches, altered mental status, seizures, visual loss, and a characteristic imaging pattern in brain magnetic resonance images. The exact etiology and pathogenesis of this condition are not yet fully elucidated. CASE PRESENTATION: A 72-year-old White man presented with 2 weeks of low-grade fever and chills, night sweats, fatigue, dysphagia, and new-onset rapidly increasing cervical lymphadenopathy. He had a history of chronic lymphocytic leukemia with transformation to diffuse large B-cell lymphoma for which he was started on dose-adjusted rituximab, etoposide, prednisone vincristine, cyclophosphamide, and doxorubicin (DA-R-EPOCH). Shortly after treatment initiation, the patient developed severe airway obstruction due to cervical lymphadenopathy that required emergency intubation. A few days later, the cervical lymphadenopathy and the status of the airway improved, and sedation was consequently weaned off to plan for extubation. However, the patient did not recover consciousness and developed generalized refractory seizures. Brain magnetic resonance imaging revealed edema in the cortical gray and subcortical white matter of the bilateral occipital and inferior temporal lobes, consistent with PRES. CONCLUSIONS: Posterior reversible encephalopathy syndrome refers to a neurological disorder and imaging entity characterized by subcortical vasogenic edema in patients who develop acute neurological signs and symptoms of a usually reversible nature in different settings, including chemotherapy. Despite its name, PRES is not always fully reversible, and permanent sequelae can persist in some patients. Clinicians should be aware of the possible association between chemotherapy and PRES to ensure early recognition and timely treatment.

[Artificial intelligence in Danish healthcare].

Artificial intelligence (AI) and machine learning have become important in medicine as shown in this review. Automatic tools can be trained to analyse patient data and thereby be a great asset to doctors when diagnosing and treating patients. Denmark is a leading country in collecting data. Having large amounts of stored data improves the quality when building a prediction tool. Due to the potential of building AI in the Danish healthcare sector, a significant amount of money has been allocated to foster new innovations in the field. Denmark could play a critical rule utilising data and implementing AI in medicine.

Nonabsorbable corticosteroids use in the treatment of gastrointestinal graft-versus-host disease.

For over a decade, nonabsorbable corticosteroids have been employed in the treatment of gastrointestinal graft-versus-host-disease (GVHD) in hematopoietic stem cell transplant (HSCT), as monotherapy or in combination with systemic corticosteroids. The majority of the evidence showing a favorable outcome consisted of case series, small phase II trials and a large randomized phase III trial. The 2 most commonly studied molecules were oral budesonide and beclomethasone diproprionate. Although these reports hint at some benefit with the local treatment strategy, their methodologic inconsistencies preclude meaningful adoption to everyday clinical practice. This review evaluates the current evidence of nonabsorbable corticosteroids in HSCT and sets forth recommendations for future trials with these agents.

Influence of plasma exchange on the disposition of the fourth generation cephalosporin cefepime.

Cefepime, a fourth generation cephalosporin, is widely used in hematology and oncology patients. These patients may require plasma exchange (PE) for indications such as chemotherapy- or cancer-induced thromobotic thrombocytopenic purpura to name a few. To date, no pharmacokinetic evaluation has been conducted assessing cefepime's disposition during PE. A 2 g IV cefepime single dose was given to patients undergoing therapeutic PE. Two hours from cefepime dose administration, plasma concentration was measured. PE was then instituted and cefepime plasmapheresate concentration was measured at the completion of the PE session. Cefepime levels were measured using HPLC. The percentage removed by PE was calculated as: amount removed/2 g dose. Ten adult patients were analyzed: median age (range): 52 years (33-67) and median weight (range); 82.85 kg (47-120). PE indications were: myasthenia gravis (n = 3), transverse myelitis (n = 2), multiple sclerosis (n = 1), chronic inflammatory demyelinating polyneuropathy (n = 1), idiopathic thrombocytopenic purpura (n = 1), thrombotic thrombocytopenic purpura (n = 1), and humoral rejection post cadaveric renal allograft (n = 1). All patients except one had a creatinine clearance >60 mL/min. One patient was excluded from the pharmacokinetic analysis owing to loss of venous access during PE. For the remaining nine patients, total plasma volume removed was 3.5 L (range: 2.5-3.5) and duration of PE was 120 min (range: 94-209). The cefepime removed by PE was 3.7% (range: 2.1-6.7). A strong correlation was found between cefepime plasma concentration prior to PE and the amount of drug removed (r = 0.96, r(2) = 0.92; p<0.05). The above results suggest that, under the studied conditions, cefepime removal by PE is clinically insignificant (approximately 4% of total 2 g dose).

[Fillet flap used for reconstruction after hemipelvectomy and amputation of a lower extremity].

In this case report, a 67-year-old woman presented with increasing pain in the left side of the thigh and pelvis. A PET scan revealed a large malignant tumour in the left side of the pelvis and proximal left femur, and an ultrasound-guided biopsy diagnosed an undifferentiated pleomorphic sarcoma. Combined orthopaedic and plastic surgery resulted in a left-sided hemipelvectomy and amputation of the left leg. The amputated left leg was used as a free fillet flap for reconstruction of the pelvis. The patient healed without complications, and seven months post-operatively she was able to use a prosthesis.

[Reconstruction by means of fillet flaps].

The purpose of this review is to summarise the literature and provide an overview of the topic and use of fillet flaps. Large and complex defects remain a reconstructive challenge balancing the benefits of reconstruction against donor-site morbidity. The spare-part concept involves using parts of amputated, non-salvageable or intact tissue for reconstruction. Fillet flaps are axial pattern flaps and can be harvested as pedicled-, island- or free flaps. Using fillet flaps for reconstruction is a valuable tool to obtain reconstruction in a one-stage procedure while minimising donor-site morbidity.

Early intervention with antithrombin III therapy to prevent progression of hepatic venoocclusive disease.

Venoocclusive disease (VOD) is the most frequent cause of early nonrelapse mortality among patients receiving high-dose chemoradiotherapy and hematopoietic stem cell transplantation. Endothelial injury of sinusoids and hepatic veins following chemotherapy is considered the initial event in the development of VOD. Activation of the coagulation cascade and inflammatory processes following endothelial injury results in a hypercoagulable state and a localized consumption of the natural anticoagulants, antithrombin III, protein C and protein S. The resultant coagulopathy can lead to multiorgan dysfunction and death. The objective was to retrospectively study the largest series of patients that has received antithrombin III for the treatment of VOD following hematopoietic stem cell transplantation. A total of 48 patients were diagnosed with VOD post hematopoietic stem cell transplantation (median age, 39 years; range, 1-69 years); 38 of the 48 received a nonradiation-based conditioning regimen and 21 of 48 received a transplant from an unrelated donor. Treatment was primarily directed at early intervention rather than prophylactic therapy to correct the antithrombin III deficiency associated with VOD. We attempted to achieve antithrombin III levels greater than 120%. There was no significant treatment-related morbidity. The overall 100-day mortality for the treatment cohort was 17%, with 10% for the mild/moderate group and 39% for the severe group, respectively. In conclusion, the encouraging results of this study suggest that this antithrombin III treatment should be further considered in patients with severe VOD.

Prurigo Nodularis after Radiotherapy: An Isoradiotopic Response?

Prurigo nodularis is a rare and chronic skin disorder with multiple, pruritic, and firm nodules. The exact pathophysiology is still unknown. Skin disorders appearing at sites of radiation can be defined as isoradiotopic. A 35-year-old male had developed a skin lesion in the left submandibular area on a base of irradiated skin which was initially suspected as a skin malignancy. The patient had a history of undifferentiated nasopharyngeal cancer with lymph node involvement which was treated by radiochemotherapy thirteen years previously. Histological examination confirmed that it was a case of prurigo nodularis which subsequently evolved at distant sites. This presentation may suggest a case of an isoradiotopic response.

Idiopathic scrotal calcinosis - A case report.

INTRODUCTION: Idiopathic scrotal calcinosis is a rare benign condition which presents with asymptomatic multiple nodules on the scrotal skin. PRESENTATION OF CASE: Our patient, a 64-year-old Indian male with Fitzpatrick skin type 4, presented with multiple nodules, which were completely surgically excised with no complications. Histological examination reveals extensive intradermal deposition of calcium surrounded by histiocytes and without cystic structure. DISCUSSION: Numerous theories about the pathogenesis have been proposed and the evidence presented suggests this is a continuum. CONCLUSION: The nature of idiopathic scrotal calcinosis is still unknown and it is up to debate whether the term "idiopathic" is appropriate for the condition.