Initiation Of Adequate Treatment Research Articles

Mucosal anomalies in autoimmune bullous diseases

Mucosal anomalies are frequently seen in autoimmune bullous diseases, particularly in pemphigus vulgaris and mucous membrane pemphigoid. The blistering, erosions, ulceration or erythema may present anywhere on the oral mucosa, but also on other mucosal sites. A differential diagnosis is needed of (erosive) oral lichen planus, systemic autoimmune disease, inflammatory bowel diseases, chronic graft-versus-host disease, infectious causes, Behçet's syndrome and recurrent aphthous stomatitis. A quick diagnosis and initiation of adequate treatment are important because of the potential severity of the disease and to prevent complications due to cicatrization. Besides a biopsy for histopathological analysis, a perilesional biopsy for direct immunofluorescence microscopy and immunoserological tests are needed for diagnosis of pemphigus or pemphigoid. In addition to a mucosal biopsy, a biopsy for direct immunofluorescence of the skin can contribute to a diagnosis of a bullous disease. Besides topical corticosteroids, immunosuppressive treatment is often required for treating autoimmune bullous diseases, such as treatment with rituximab in patients with pemphigus.

Stent jako řešení perforace „černého jícnu“

Summary: “Black esophagus”, also known as acute esophageal necrosis (AEN), is a relatively rare disease characterized by black discoloration of the esophageal mucosa. The condition can be located only distally, but it can also affect the entire esophagus. Hematemesis is the most common clinical manifestation is; the condition is associated with increased lethality in high-risk groups of patients. Early diagnosis of AEN can be made by gastroscopy, the initiation of adequate treatment is crucial for a favorable patient prognosis. The most serious complications of AEN include esophageal perforation with the risk of other complications such as mediastinitis and sepsis. The nature of the disease and the affection of the esophagus and potentially the mediastinum require a multidisciplinary approach. Below we present a case report of a 68-year-old patient with a diagnosis of AEN complicated by perforation confirmed by CT and early endoscopy. An endoscopic approach with the introduction of a fully coated metal stent was chosen as the primary solution for the esophageal perforation. Nevertheless, the patient developed other complications of perforation: mediastinitis and empyema requiring chest drainage. In addition to interventional methods, the patient was treated with broad-spectrum antibiotics and a combination of parenteral and enteral nutrition. After 3 months of treatment and resolving the complications, the patient was released to outpatient care in a good clinical condition. Key words: acute esophageal necrosis – oesophageal perforation – mediastinitis – Danis stent – metallic stent

Case Report: Role of transesophageal echocardiography in a patient with an initially misdiagnosed acute pulmonary embolism

Background: For the diagnosis of acute pulmonary embolism, chest computerized tomography (CT) angiography is considered as the gold standard. However, echocardiography could be useful especially in cases of high suspicion with normal CT scan or for patient with hemodynamic instability. Case presentation: We present a case of a 47-year-old man admitted to the intensive care unit with a diagnosis of respiratory failure and hemodynamic instability 24 hours after closed fracture of the right leg. Before his admission, a thoracic CT angiography was done but did not show any sign of acute pulmonary embolism. During the first hours, he presented a bad evolution with a respiratory status which failed to respond to high dose of vasopressor, oxide nitric and ventilatory support. Therefore, due to the poor echocardiographic window, transesophageal echocardiography examination was done in emergency. It revealed high-probability diagnosis of massive pulmonary embolism based on right ventricular dysfunction and the presence of thrombus in the right pulmonary artery. Anticoagulant therapy (non-fractioned heparin) was administrated immediately achieving a favorable clinical outcome with rapid withdrawal of dobutamine, nitric oxide and norepinephrine. Conclusions: This case illustrates the fundamental role of transesophageal echocardiography in a critically ill patient with shock due to high-probability pulmonary embolism. Echocardiography allows the initiation of adequate treatment without further delay.

Complex Regional Pain Syndrome or Limb Pain: A Plea for a Critical Approach.

Most frequently, complex regional pain syndrome (CRPS) develops after a trauma and affects distal parts of the limbs. Early recognition and initiation of adequate treatment is crucial for a favorable outcome. On the other hand, misdiagnosing other disorders as CRPS is detrimental because more appropriate treatment may be withheld from the patients. Despite intensive research, a specific biomarker or paraclinical measure for CRPS diagnosis is still lacking. Instead, clinical criteria approved by the International Association for the Study of Pain (IASP) and latest adapted in 2019 are central for diagnosing CPRS. Thus, the CRPS diagnosis remains challenging with the risk of a “deliberate diagnosis” for unexplained pain, while at the same time a delayed CRPS diagnosis prevents early treatment and full recovery. CRPS is a diagnosis of exclusion. To clinically diagnose CRPS, a vigorous exclusion of “other diseases that would better explain the signs and symptoms” are needed before the patients should be referred to tertiary centers for specific pain treatment. We highlight red flags that suggest “non-CRPS” limb pain despite clinical similarity to CRPS. Clinical and neurological examination and paraclinical evaluation of a probably CRPS patient are summarized. Finally, we pinpoint common differential diagnoses for CRPS. This perspective might help CRPS researchers and caregivers to reach a correct diagnosis and choose the right treatment, regardless whether for CRPS mimics or CRPS itself.

Diagnosis of interstitial cystitis: practice-orientated diagnostic work-up

Interstitial cystitis is a chronic orphan disease of the urinary bladder characterised by its main symptoms of bladder pain, persistent urge to void and urinary frequency. Due to a variety of confusable diseases and different pathophysiologies, the diagnosis of IC is still a diagnosis of exclusion and remains a challenge for doctors and patients alike. Patients often experience misdiagnosis and unsuccessful treatment for years. Therefore, the primary goal for these patients with chronic pain must be a rapid diagnosis and initiation of adequate treatment. This article focuses on transferring the consensus-based recommendations of the current German S2k guideline "Diagnosis and Treatment of Interstitial Cystitis" (IC/BPS) (2018 AWMF register No.: 043/050) into a practice-orientated and structured diagnostic work-up process.

Hypoadrenocorticism in dogs – the Mad Hatter of veterinary internal medicine

Hypoadrenocorticism arises from insufficient adrenal gland function and is also known as Addison’s disease, a rarely occurring disease (0.1%) in dogs. Due to its oscillatory course and overall nonspecific symptoms, it is a diagnostic challenge for clinicians, and is often misdiagnosed or unattended among other differentials. There are two forms of hypoadrenocorticism: primary and secondary. The aim of this study was to analyse the data of dogs suffering from Addison’s disease, treated at the Clinic for Internal Medicine, Faculty of Veterinary Medicine, University of Zagreb, Croatia and to compare them with data from similar institutions worldwide. The archive of Clinic for Internal Medicine, Faculty of Veterinary Medicine, Zagreb, Croatia was searched to investigate and statistically analyse signalment, clinical and laboratory data, and the duration of symptoms, treatment protocols and outcome of canine hypoadrenocorticism. The study group included 14 dogs (36% male and 64% female) diagnosed with hypoadrenocorticism. All dogs had a history of gastrointestinal symptoms, i.e. vomiting in 100%, diarrhoea in 64% and melena in 7%. Hypovolemic shock was noted in 57%, hypothermia in 64% and bradycardia in 29% of cases. The most frequently observed laboratory abnormalities were an increase in BUN (86%), creatinine (57%) and potassium concentration (79%), and a decrease in sodium (71%), Na/K ratio (86%), cholesterol (21%) and glucose concentration (21%). Duration of symptoms (till ACTH stimulation test performance) was broad, from 2 – 2190 days (median 90±1195.5 days). The outcome was favourable in 100% cases after initiation of adequate treatment.

STRUCTURE OF SURGICAL ABNORMALITY IN NEWBORNS OF THE NIZHNY NOVGOROD REGION

Introduction.A tendency to the decline in birth rate and reduced number of diseases of the neonatal period has been lately observed in the Nizhny Novgorod region.Materials and methods. 494 neonates with a surgical pathology aged from the frst hours to several weeks were treated in hospitals serving as clinical bases for the Volga Research Medical University from 2013 to 2017. 305 (62%) boys and 189 (38%) girls were observed. The majority of children (88%) were taken to surgical departments from maternity homes and perinatal centers of the city and region. 62 (12%) of children were hospitalized following the referral from local pediatricians. Admitted patients had a clinical and instrumental examination and initial therapy that stabilized their conditions and prepared them for surgeries.Results. Congenital malformations (CM) were diagnosed in 330 (67%) children only. According to analysis of diseases related to the neonatal period, purulent and septic processes were found in 104 (21%) patients. Surgeries were performed in children aged from day 1 to several months of life.Conclusion. Modern antenatal diagnostics and complex examination of newborns in the neonatal period enable timely detection of congenital abnormalities and initiation of adequate treatment.

Different Presentations of Patients with Transcobalamin II Deficiency: A Single-Center Experience from Turkey

Objective:Transcobalamin II deficiency is a rare autosomal recessive disease characterized by decreased cobalamin availability, which in turn causes accumulation of homocysteine and methylmalonic acid. The presenting clinical features are failure to thrive, diarrhea, megaloblastic anemia, pancytopenia, neurologic abnormalities, and also recurrent infections due to immune abnormalities in early infancy.Materials and Methods:Here, we report the clinical and laboratory features of six children with transcobalamin II deficiency who were all molecularly confirmed.Results:The patients were admitted between 1 and 7 months of age with anemia or pancytopenia. Unexpectedly, one patient had a serum vitamin B12 level lower than the normal range and another one had nonsignificantly elevated serum homocysteine levels. Four patients had lymphopenia, four had neutropenia and three also had hypogammaglobulinemia. Suggesting the consideration of transcobalamin II deficiency in the differential diagnosis of immune deficiency. Hemophagocytic lymphohistiocytosis was also detected in one patient. Furthermore, two patients had vacuolization in the myeloid lineage in bone marrow aspiration, which may be an additional finding of transcobalamin II deficiency. The hematological abnormalities in all patients resolved after parenteral cobalamin treatment. In follow-up, two patients showed neurological impairments such as impaired speech and walking. Among our six patients who were all molecularly confirmed, two had the mutation that was reported in transcobalamin II-deficient patients of Turkish ancestry. Also, a novel TCN2 gene mutation was detected in one of the remaining patients.Conclusion:Transcobalamin II deficiency should be considered in the differential diagnosis of infants with immunological abnormalities as well as cytopenia and neurological dysfunction. Early recognition of this rare condition and initiation of adequate treatment is critical for control of the disease and better prognosis.

Improving the Outcomes of Acute Promyelocytic Leukemia in a Limited Resources Setting: The Benefit of Early ATRA Administration in 30-Day Survival

▪ INTRODUCTIONAcute promyelocytic leukemia (APL) is the most curable acute leukemia in adults. Advancements in therapeutics such as the use of tretinoin (ATRA) and arsenic trioxide (ATO) have led to an overall survival of over 90% in 5 years. Early mortality, however, remains a major component of overall mortality in this disease and prompt recognition and initiation of adequate treatment has always been considered the most effective strategy to prevent it. Recent reports, though, have failed to show the benefit of prompt ATRA ministration in early mortality, once APL is suspected. These reports come mainly from high-income countries with swift and widespread access to health care services that are capable of recognizing, diagnosing and treating APL in a timely manner.We hypothesized, therefore, that in a lower income country, in a limited resources setting, prompt ATRA administration would improve early mortality in the setting of APL. METHODSThis is a retrospective, single-center study. We included all patients with APL diagnosis, confirmed by molecular or cytogenetics analysis treated in our institution, from January 1999 to May 2018. Until 2006, patients were treated with a modified AIDA regimen (ATRA plus mitoxantrone). After 2006, patients were treated with the International Consortium on Acute Promyelocytic Leukemia - ICAPL protocol (ATRA plus daunorubicin). This was a combined effort of the American Society of Hematology and of healthcare institutions from Latin American countries to improve outcomes in APL through improvements in therapeutics, education of healthcare professionals and expanded access to molecular diagnosis.We retrieved and reviewed patients' records for the time interval from disease presentation until the first hospital admission, and from hospital admission to the first dose of ATRA. We also looked for diagnostic variables that could be related with 30-day survival. RESULTSBetween January 1999 and May 2018, 83 APL patients were evaluated. Table 1 summarizes patients' characteristics. Medical records were available for 81/83 patients; 4 of them did not receive ATRA and died less than 7 days after their presentation. At diagnosis, median age was 37 years, 51.9% of patients were female, 26% were high-risk, 77.8% had bleeding symptoms, 72.8% had abnormal coagulation tests, and 12.3% had an elevated serum creatinine. Seventy-five percent were treated under the IC-APL protocol. Median time from disease presentation to the first hospital admission was 14.3 days (1-64 days) and median time to administration of ATRA after hospital admission was 18.2 hours (0.47-95.47 hours). Time to ATRA administration was significantly higher in patients who died in the first 30 days after diagnosis (median 27.46 vs.15.52 hours p=0.037) and who were treated with the modified AIDA (median 25.04 hours for the modified AIDA vs. 15.2 hours for the IC-APL protocol, p=0.037).Early administration of ATRA (less than 24 hours after the first hospital admission) was associated with a higher 30-day survival (89.4% vs. 63.3%, p=0.007; 75.3% for the whole cohort - Figures 1A and B). This benefit was seen mainly in patients with low or intermediate Sanz's risk score (Figures 1C and D). Serum creatinine, leukocytes count, and Sanz's risk were also predictive of 30-day survival in the whole cohort. There was no correlation between time from disease presentation to first hospital admission with 30-day survival.CONCLUSIONS: Our data support the role of early ATRA administration in the reduction of 30-day mortality in patients with recently diagnosed APL. This contrasts with previous findings from high-income countries that did not support such a benefit. We should highlight that in these cohorts the median time for ATRA administration was longer, which could explain the conflicting results. Furthermore, patients in high-income countries access health services early in their disease course, which could hamper any benefit from early ATRA administration.The correlation of early ATRA administration with the institution of IC-APL protocol underscores the importance of initiatives that promote the education of healthcare professionals and access to diagnostic tests of complex hematological diseases in low-income settings. DisclosuresPagnano:Abbvie: Consultancy; EMS: Other: Financial support for participation in congress; Novartis: Consultancy; Shire: Other: Lecture.

Effect of Delay In Starting Adequate Treatment On Recovery Time Of Head And Neck Space Infections

Aim: This prospective observational study was conducted to find out “delay of starting adequate treat- ment” as a prognosis predictor of head and neck space infections.Material and method:50 patients were selected purposively with inclusion criteria of presence of head and neck space infections. The exclusion criteria was presence of any other co-morbid diseases. After proper evaluation and diagnosis, adequate treatment was provided. Structured questioner method was used to collect data related to delay of starting of treatment and outcome of disease.Result: In this prospective observational study, caries was the most frequent cause of space infection. Time elapsed in between starting of symptoms and initiation of adequate treatment (timing of starting treatment) was 8.52(±6.689) days. This delay of starting treatment causing increased recovery time significantly (P= < 0.001 level). However, there was no correlation in between delay of starting treat- ment and number of involved space infection but later has impact on recovery time.Conclusion: Information about delay of starting treatment and number of involved spaces can be used as a prognosis predictor in HNSI.Update Dent. Coll. j: 2018; 8 (1): 41-44

Bloodstream infection caused by S. aureus in patients with cancer: a 10-year longitudinal single-center study.

Staphylococcus aureus bloodstream infections (SABIs) represent a significant cause of morbidity and mortality in cancer patients. In this study, we compared infection characteristics and evaluated epidemiology and risk factors associated to SABIs and 30-day attributable mortality in cancer patients. Clinical and microbiological data from patients with cancer and positive blood cultures for S. aureus were retrieved during a 10-year period at an oncology reference center. Analyses were performed according to type of malignancy and infection with methicillin-resistant S. aureus (MRSA). Data was evaluated using competing risk analyses to identify risk factors associated to 30-day mortality and used to create a point system for mortality risk stratification. We included 450 patients and MRSA was documented in 21.1%. Hospital-acquired infection, healthcare-associated pneumonia, and type-2 diabetes were associated to MRSA. In patients with hematologic malignancies, MRSA was more frequent if hospital-acquired, but less likely in primary bacteremia. Variables associated to mortality included abdominal source of infection, hematologic malignancy, MRSA, glucose levels > 140mg/dL, and infectious endocarditis; catheter removal and initiation of adequate treatment within 48h of positive blood culture were protective factors. From our designed mortality prediction scale, patients with a score > 3 had a 70.23% (95%CI 47.2-85.3%) probability of infection-related death at 30days. SABIs are a significant health burden for cancer patients. Risk factors for SABI-related mortality in this population are varied and impose a challenge for management to improve patient's outcomes. Risk stratification might be useful to evaluate 30-day mortality risk.

Cardiac Rhythm Disturbances in Hemodialysis Patients: Early Detection Using an Implantable Loop Recorder and Correlation With Biological and Dialysis Parameters.

The aim of this study was to identify using implantable loop recorder (ILR) monitoring the mechanisms leading to sudden death (SD) in patients undergoing hemodialysis (HD). SD accounts for 11% to 25% of death in HD patients. Continuous rhythm monitoring was performed using the remote monitoring capability of the ILR device in patients undergoing HD at 8 centers. Clinical, biological, and technical HD parameters were recorded and analyzed. Seventy-one patients (mean age 65 ± 9 years, 73% men) were included. Left ventricular ejection fraction was<50% in 16%. Twelve patients (17%) had histories of atrial fibrillation or flutter at inclusion. During a mean follow-up period of 21.3 ± 6.9 months, 16 patients died (14% patient-years), 7 (44%) of cardiovascular causes. Four SDs occurred, with progressive bradycardia followed by asystole. The incidence of patients presenting with significant conduction disorder and with ventricular arrhythmia was 14% and 9% patient-years, respectively. In multivariate survival frailty analyses, a higher risk for conduction disorder was associated with plasma potassium >5.0 mmol/l, bicarbonate<22 mmol/l, hemoglobin >11.5 g/dl, pre-HD systolic blood pressure >140 mmHg, the longer interdialytic period, history of coronary artery disease, previous other arrhythmias, and diabetes mellitus. A higher risk for ventricular arrhythmia was associated with potassium<4.0 mmol/l, no antiarrhythmic drugs, and previous other arrhythmias. With ILR monitoring, de novo atrial fibrillation or flutter was diagnosed in 14 patients (20%). ILR may be considered in HD patients prone to significant conduction disorders, ventricular arrhythmia, or atrial fibrillation or flutter to allow early identification and initiation of adequate treatment. Therapeutic strategies reducing serum potassium variability could decrease the rate of SD in these patients. (Implantable Loop Recorder in Hemodialysis Patients [RYTHMODIAL]; NCT01252823).

A Case of Rare Diffuse Alveolar Hemorrhage and Review of Literature.

It is well known that some disorders can cause concomitant kidney dysfunction with lung involvement. These syndromes, characterized by the simultaneous presence of intra-alveolar hemorrhage and acute glomerulonephritis, are caused by numerous and variable disorders. The most frequent are the antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis and Goodpasture syndrome. A quick discerning of the underlying causes and initiation of adequate treatment is crucial to prevent acute respiratory failure and irreversible loss of renal function. We reported the case of a 33-year-old man having hemorrhagic alveolitis presenting a picture consistent with Goodpasture syndrome in the absence of anti-glomerular basement membrane (anti-GBM) antibodies or ANCA at lab test and a review of literature. This case highlights the need to consider the chances of falsely seronegative cases of anti-GBM disease, as well as the importance of using all available assay routine tests. These cases would appear indeed more common than before if just taken into consideration their existence. Several reports have shown false seronegatives especially in patients with relapses, in smokers, and in patients with predominantly pulmonary symptoms.

Caractéristiques cliniques et évolutives du lichen plan unguéal : étude descriptive de 20 patients

Nail lichen planus (NLP) occurs in 10% of patients with disseminated disease but it can also occur in isolation. The outcome of treatment is usually disappointing and data about its long-term prognosis are lacking. To study clinical features, response to treatment and follow-up of a series of 20 patients with NLP. A descriptive study was conducted of 20 patients with histologically confirmed NLP seen at consultations for nail disorders between September 2009 and April 2013. The mean age was 35 years (9-56 years) with no gender preponderance. Forty percent of patients were children. Stress was an evident triggering factor in 20% of patients. The mean duration was around 48 months (2 months to 10 years). Only 25% of patients had extra-ungual lesions. All 20 nails were affected in 55% of patients. Nail matrix involvement was observed in 85% of cases and 55% had nail-bed involvement. Twenty-five percent of patients were presenting severe involvement such as pterygium or anonychia. Intramuscular corticosteroids were given to 10 patients. In 80% of patients, the NLP was limited or regressed rapidly from the third injection. The average follow-up was 24 months. Our study highlights the frequency of paediatric forms and of often aesthetically unacceptable nail scarring. Early diagnosis of NLP, notably in children, would allow initiation of adequate treatment that could perhaps limit the risk of such sequelae.

BECTS evolving to Landau–Kleffner Syndrome and back by subsequent recovery: A longitudinal language reorganization case study using fMRI, source EEG, and neuropsychological testing

By means of a longitudinal case study, we demonstrated the course of cerebral reorganization of language representation due to epilepsy in a child with benign epilepsy with centro-temporal spikes (BECTS) evolving to Landau–Kleffner Syndrome (LKS) and returning to BECTS.The child underwent the following procedures at the ages of 8.2, 8.6, and 9.3years: 3D source EEG imaging, language fMRI (sentence generation and reading), and neuropsychological testing. He had a follow-up testing at the age of 10.8years. Further, 24-h EEGs were regularly performed.At the age of around 8years, the child was diagnosed initially with left-hemispheric BECTS, which evolved to LKS with continuous bilateral discharges. In addition, 3D source imaging data revealed a left anterior temporal focus with a spreading to the right parietal and left centro-parietal areas. The patient had verbal agnosia with poor verbal yet good performance indices. Functional magnetic resonance imaging (fMRI) showed a left-hemispheric reading network but sentence generation was impossible to perform. After initiation of adequate treatment, continuous discharges disappeared, and only very rare left-hemispheric centro-temporal spikes remained. Verbal IQ and performance IQ increased at the age of 8.6years. Functional magnetic resonance imaging showed, at this time, a right-hemispheric language activation pattern for sentence generation and reading. At the ages of 9.3 and 10.8years, language tasks remained right-hemispheric and verbal IQ remained stable, but right-hemispheric non-verbal functions decreased due to possible crowding-out mechanisms.

Enterocolitis in a Patient Being Treated With Ipilimumab for Metastatic Melanoma

Question: A 69-year-old man with a suprasternally localized 3-cm skin mass and multiple lung metastases was referred for treatment. The tumor was completely excised, and histology revealed a nodular malignant melanoma (Clarke level V, tumor thickness 12 mm). Subsequently, chemotherapy with dacarbazine (DTIC) was started. After tumor progression, second-line treatment with ipilimumab was initiated. In the further course, the patient developed fevers and a watery diarrhea without hematochezia. Imaging studies did not show any signs of infection. A slightly elevated C-reactive protein, leukocytosis, and lymphopenia were noted. Routine microbiological testing of blood and stool samples were negative for pathogenic bacteria, Clostridium difficile toxin, parasites, rotavirus, cytomegalovirus, Epstein–Barr virus, and tuberculosis. The patient refused a colonoscopy at that time. An empiric antibiotic therapy with piperacillin and tazobactam and oral methylprednisolone 40 mg/d was started. At the time of discharge, symptoms had improved, although the patient complained about up to 4 soft bowel movements per day. A few days later, he was readmitted again with watery diarrhea. Colonoscopy showed discontinuous, multiple, deep ulcerations (maximum size, 3 cm) throughout the colon (Figure A). The rectum was spared and no fistulas were noted. Microbiological examination of biopsies did not reveal any pathogenic germs. Histologic examinations confirmed ulcerative epithelial defects with lymphocytic infiltrates and capillary-rich granulation tissue (Figure B; provided with kind permission of Professor Hans-Michael Kvasnicka, MD, Senckenbergisches Institut für Pathologie, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany). What is the diagnosis? Look on page 504 for the answer and see the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI. The patient developed an immune-related enterocolitis after treatment with ipilimumab. Ipilimumab is a fully human immunoglobulin (Ig)G1 monoclonal antibody against cytotoxic T-lymphocyte–associated antigen 4, which can induce anti-tumor immunity. In a pivotal clinical trial, patients with previously treated unresectable stage III or IV melanoma were treated with a gp100 vaccine with or without ipilimumab.1Hodi F.S. O'Day S.J. McDermott D.F. et al.Improved survival with ipilimumab in patients with metastatic melanoma.N Engl J Med. 2010; 363: 711-723Crossref PubMed Scopus (11247) Google Scholar In this study, ipilimumab (3 mg/kg) improved the overall survival, regardless of a concomitant gp100 vaccination (ipilimumab group, 10.1 months; gp100 group, 6.4 months; hazard ratio [HR], 0.66; P = .003). Thus, ipilimumab was recently approved as monotherapy for adult patients with advanced malignant melanoma who have received prior therapy. In this study, the incidence of a grad 3/4 immune-mediated enterocolitis was 5%. Moreover, ipilimumab (10 mg/kg) plus DTIC improved overall survival in patients with previously untreated metastatic melanoma (ipilimumab plus DTIC, 11.2 months; placebo plus DTIC, 9.1 months; HR, 0.72; P < .001).2Robert C. Thomas L. Bondarenko I. et al.Ipilimumab plus dacarbazine for previously untreated metastatic melanoma.N Engl J Med. 2011; 364: 2517-2526Crossref PubMed Scopus (3579) Google Scholar Immune-related gastrointestinal events were the most frequent side effects after ipilimumab treatment, with grade 3/4 toxicity in 7.6% of patients. Noteworthy, in this study no bowel perforations or drug-related deaths occurred. Immune-related enterocolitis and diarrhea after ipilimumab usually respond to steroid treatment and should be managed according to published algorithms to avoid severe complications such as bleeding and perforation.3Kaehler K.C. Hauschild A. Treatment and side effect management of CTLA-4 antibody therapy in metastatic melanoma.J Dtsch Dermatol Ges. 2011; 9: 277-286Crossref PubMed Scopus (96) Google Scholar After the diagnosis of an immune-related enterocolitis, our patient was treated with a pulse therapy with IV prednisolone (250 mg/d). Additionally, he received parenteral nutrition and IV hydration. He responded to the treatment promptly and was started again on enteral nutrition and oral methylprednisolone with a slow taper over 8 weeks. Follow-up sigmoidoscopy after 4 weeks showed single, healing ulcerations. At this time, the diarrhea had completely resolved and tumor stabilization was documented. In summary, instructions about relevant symptoms and an early diagnosis and initiation of adequate treatment are essential for prevention of severe complications of an immune-related enterocolitis in patients being treated with ipilimumab.

Hemophagocytic lymphohistiocytosis as severe adverse event of antineoplastic treatment in children

Hemophagocytic lymphohistiocytosis (HLH) during childhood cancer treatment is a rare adverse event posing major diagnostic and therapeutic challenges. Between 1995 and 2006, 6 children developed HLH while on conventional chemotherapy (n=4) or after allogeneic stem cell transplantation (n=2). Treatment of HLH included dexamethasone and etoposide, 2 children additionally received infliximab or daclizumab. Three children survived, whereas 3 children died 2, 5, and 47 days after diagnosis of HLH. HLH is a severe adverse event of childhood cancer therapy. Early diagnosis and immediate initiation of adequate treatment are mandatory to overcome this severe condition.

Increased Risk for Atherosclerosis Estimated by Pulse Wave Velocity in Hypothyroidism and its Reversal with Appropriate Thyroxine Treatment

Pulse wave velocity (PWV) is known to represent arterial stiffness and is established as a marker for cardiovascular risk and a prognostic factor for mortality in the case of chronic renal failure or hypertension. The application of an automated apparatus for measuring brachial-ankle pulse wave velocity (baPWV) has made PWV measurement non-invasive, easier to screen for cardiovascular risk and as a result, baPWV measurements have become widely applied in clinical practice in recent years. We assessed the baPWV in 7 flank hypothyroidism patients and 28 subclinical hypothyroidism patients. In comparison with age matched healthy controls, 3 hypothyroid patients had advanced values and by replacement therapy, all 7 subjects showed improvement in their baPWV values (1531.2 +/- 242.7 to 1330.2 +/- 208.6 cm/s, p<0.05). In 28 subclinical hypothyroid subjects, 71% also had accelerated baPWV values for their age. Ten subjects (36% of all) had neither hypertension, hyperlipidemia, diabetes nor were taking any medication, and yet 8 patients out of 10 showed advanced baPWV values compared to age matched mean values. The baPWV was not correlated to TSH or total cholesterol levels, and was associated with only age and blood pressure (p = 0.01, <0.001, respectively), which are widely demonstrated as the characteristics for baPWV. In two subclinical hypothyroid subjects, who were normotensive and had no dyslipidemia, thyroxine treatment was performed and the baPWV decreased with unchanged blood pressure and total cholesterol levels. We concluded that the arterial wall stiffness tends to be increased in both overt and subclinical hypothyroid patients, and an appropriate treatment could reverse the abnormalities. It is possible that the initiation of adequate treatment in subclinical hypothyroidism may reduce the cardiovascular risk.

Neuro‐ophthalmological findings in sarcoidosis

This review emphasizes the importance of neuro-ophthalmological signs and symptoms in sarcoidosis. The presence of ophthalmological and neuro-ophthalmological findings may lead to diagnosis of the disease and the initiation of adequate treatment. Patients who had been diagnosed with neurosarcoidosis during the period 1990 - 2001 were identified from the departmental diagnostic index. The history, clinical, laboratory and imaging data of patients were analysed. Fifteen patients were identified, four men and 11 women, with a mean age of 44.1 years (range 26-65 years). In six of the 15 (40%), neurological deficits were the initial symptoms. Nine (60%) had known sarcoidosis at the time of presentation. Ten patients (66%) had ophthalmological/neuro-ophthalmological symptoms and signs. Neuro-ophthalmological symptoms may develop early in neurosarcoidosis. If neuro-ophthalmological symptoms arise in patients with established biopsy-proven sarcoidosis, the diagnosis is usually easy to make. However, a number of patients with neurosarcoidosis may present with neuro-ophthalmic symptoms before systemic involvement becomes obvious. In this situation the diagnosis is challenging, and the major goal is to establish the presence of systemic sarcoidosis.

Prognostic value of anti-Plasmodium falciparum-specific immunoglobulin G3, cytokines, and their soluble receptors in West African patients with severe malaria.

Forty-one African patients suffering from clinically defined severe malaria were studied in the intensive medical care unit of the main hospital in Dakar, Senegal, West Africa. All of these individuals lived in Greater Dakar, an area of low and seasonal Plasmodium falciparum endemicity. Twenty-seven patients (mean age +/- 1 standard deviation, 19.2 +/- 12.7 years) survived this life-threatening episode, but 14 (30.8 +/- 16.2 years old) died despite initiation of adequate treatment. On the day of admission (day 0) and 3 days later, one to two blood samples (i.e., approximately 10 to 15 ml) were obtained from each subject, and different biological parameters were evaluated in the two groups. Plasma samples were tested for their content in tumor necrosis factor alpha (TNF-alpha), soluble receptors I and II for TNF-alpha (TNF-alpha sRI and TNF-alpha sRII), interleukin-6 (IL-6), IL-6 sR, IL-10, and IL-2 sR. The concentrations of all these cytokines and/or their receptors was significantly elevated in patient plasma samples on day 0, and it rapidly decreased in the group of individuals who survived. By comparison, the mean concentration of the same parameters decreased slowly in the group of patients who died (except for IL-10, which dramatically fell in all patient plasma samples soon after initiation of antimalarial treatment). The TNF-alpha sRI level remained significantly elevated among the patients who died, and the highest levels of soluble TNF-alpha sRI receptor were found among the older patients. Parasite-specific immunoglobulin M (IgM), total IgG, IgG1, IgG2, IgG3, and IgG4 were evaluated by enzyme-linked immunosorbent assay using a crude extract of a local P. falciparum isolate as antigen and human class- and subclass-specific monoclonal antibodies. Parasite-specific IgM, total IgG, and IgG1 were detectable in the plasma samples of most of these African patients, whereas IgG2 and IgG4 mean values were low. The mean level of parasite-specific IgG3 was different (P = 0.024) at day 0, i.e., before initiation of intensive medical care, between the group of the 27 surviving subjects and the group of 14 patients dying of severe malaria. As a consequence, most of the African patients who died had only trace amounts or almost no detectable level of parasite-specific IgG3 at the time of admission. In contrast, the presence of even limited IgG3 activity at day 0 was found to be associated with a significantly increased probability of recovering from severe malaria. Therefore, in our study, both an elevated level of TNF-alpha sRI and absence of IgG3 activity were of bleak prognostic significance, whereas a favorable outcome was usually observed when parasite-specific IgG3 activity was detectable. This finding was strongly suggestive of a prime role for these parasite-specific immunoglobulins in the capacity to help recovery from severe malaria.