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Background Ibrutinib is an oral inhibitor of Bruton’s tyrosine kinase (BTK) that is FDA-approved for several lymphoproliferative disorders and chronic GVHD. Objective To characterize cutaneous eruptions arising from ibrutinib and highlight overlap with epidermal growth factor receptor inhibitor (EGFRi)-induced dermatologic adverse events (dAEs). Methods Single-center retrospective cohort of patients referred to the Skin Toxicities Program for management of cutaneous eruptions while taking ibrutinib. Results Among 19 patients, cutaneous eruptions manifested as facial-predominant papulopustular eruptions, petechiae or ecchymoses, photosensitivity, panniculitis, xerosis, and clinical staphylococcal overgrowth. The majority of patients were able to continue ibrutinib therapy with focused management of their cutaneous toxicities. Limitations This study represents cases at a single tertiary care center and is limited to patients referred for toxicity. Conclusions With the exception of petechiae, the cutaneous toxicities of ibrutinib overlap with those associated with selective EGFR inhibitors. We observed that these reactions can be successfully managed using approaches for EGFR inhibitor-induced cutaneous adverse events.

Recognizing sport-related concussion (SRC) is challenging and relies heavily on subjective symptom reports. An objective, biological marker could improve recognition and understanding of SRC. There is emerging evidence that salivary micro-ribonucleic acids (miRNAs) may serve as biomarkers of concussion; however, it remains unclear whether concussion-related miRNAs are impacted by exercise. We sought to determine whether 40 miRNAs previously implicated in concussion pathophysiology were affected by participation in a variety of contact and non-contact sports. Our goal was to refine a miRNA-based tool capable of identifying athletes with SRC without the confounding effects of exercise.This case-control study harmonized data from concussed and non-concussed athletes recruited across 10 sites. Levels of salivary miRNAs within 455 samples from 314 individuals were measured with RNA sequencing. Within-subjects testing was used to identify and exclude miRNAs that changed with either: (a) a single episode of exercise (166 samples from 83 individuals) or (b) season-long participation in contact sports (212 samples from 106 individuals). The miRNAs that were not impacted by exercise were interrogated for SRC diagnostic utility using logistic regression (172 samples from 75 concussed and 97 non-concussed individuals).Two miRNAs (miR-532-5p, miR-182-5p) decreased (adjusted p0.05) after a single episode of exercise, and 1 miRNA (miR-4510) increased only after contact sports participation. Twenty-three miRNAs changed at the end of a contact sports season. Two of these miRNAs (miR-26b-3p, miR-29c-3p) were associated (R0.50; adjusted p0.05) with the number of head impacts sustained in a single football practice. Among the 15 miRNAs not confounded by exercise or season-long contact sports participation, 11 demonstrated a significant difference (adjusted p0.05) between concussed and non-concussed participants, and 6 displayed moderate ability (AUC0.70) to identify concussion. A single ratio (miR-27a-5p/miR-30a-3p) displayed the highest accuracy (AUC = 0.810, sensitivity = 82.4%, specificity = 73.3%) for differentiating concussed and non-concussed participants. Accuracy did not differ between participants with SRC and non-SRC (z = 0.5, p = 0.60).Salivary miRNA levels may accurately identify SRC when not confounded by exercise. Refinement of this approach in a large cohort of athletes could eventually lead to a non-invasive, sideline adjunct for SRC assessment.

A fetus with features of hydrops was given intra-uterine transfusion at 27 weeks and 31 weeks of gestation. Mother had been alloimmunized with anti-D and anti-C antibodies. At birth, laboratory investigations revealed bone marrow suppression along with features of hemolytic anemia. The neonate was started on a combination of phototherapy and intravenous immunoglobulin. During the course, the neonate was transfused with one unit of packed red cells (top-up transfusion). Neonatal hyperbilirubinemia responded to phototherapy and the bone marrow activity spontaneously resumed after 3 weeks of life. In neonates with anemia at birth who have history of multiple intra-uterine transfusions, early-onset hypoproliferative anemia should be considered.

Transient loss of consciousness (TLOC) is a frequent cause of referral to an emergency room. In view of the impact on treatment and the patients’ daily life activities (e. g. profession, driving license), an accurate and timely diagnosis is of uttermost importance. This article provides key features and suggests a practical step-by-step approach of how to differentiate syncope, epileptic and psychogenic non-epileptic seizures as the commonest causes of nontraumatic TLOC.

Abstract: Lipoprotein(a)(Lp[a]) is a low-density lipoprotein-cholesterol (LDL-C)-like particle with potent pro-atherothrombotic properties. The association of Lp(a) with several circulating factors, including vitamins, remains unresolved. We performed an observational analysis using the National Health and Nutrition Examination Survey III cohort, a cohort used to monitor the nutrition status of US-citizens. We used multivariable linear regression to test associations of Lp(a) and LDL-C with levels of serum vitamins and minerals and whole-blood lead. Analyses controlled for factors known to associate with Lp(a) (age, sex, race/ethnicity, statin use, hemoglobin A1c, body mass index, hypertension, diabetes, glomerular filtration rate, alcohol intake, and saturated fat intake). LDL-C was corrected for Lp(a) mass. Multiple sensitivity tests were performed, including considering factors as categorical variables (deficient, normal, elevated). Among 7,662 subjects, Lp(a) correlated (β-coefficient) positively (change per 1 conventional unit increase) with carotenoids (lycopene (0.17(0.06,0.28), p=0.005), lutein (0.19(0.07,0.30), p=0.002), β-cryptoxanthin (0.21(0.05,0.37), p=0.01), β-carotene (0.05(0.02,0.09), p=0.003), and α-carotene (0.15(0.01,0.30), p=0.04)) and lead (0.54(0.03,1.05), p=0.04) levels when tested as continuous variables. LDL-C had similar associations. Lp(a) did not associate with vitamins A, B12, C, or E retinyl esters, folate, RBC-folate, selenium, ferritin, transferrin saturation, or calcium. With factors as categorical variables, Lp(a) but not LDL-C negatively associated with elevated vitamin B12 (−5.41(−9.50, −1.53), p=0.01) and folate (−2.86(−5.09, −0.63), p=0.01). In conclusion, Lp(a) associated similarly to LDL-C when vitamins, minerals, and lead were tested as continuous variables, while only Lp(a) correlated with vitamin B12 and folate when tested as categorical variables. These observations are hypotheses generating and require further studies to determine causality.

Cystic hydatid disease or cystic echinococcosis (CE) is a globally endemic zoonosis caused by the larval cyst stage of the tapeworm Echinococcus granulosus. Concomitant presence of CE and hepatocellular carcinoma (HCC) is a rare clinical scenario. A 70-year-old male patient presented with acute abdominal pain to the surgical outpatient department. On evaluation, a cystic lesion with solid components and free fluid in the abdomen was observed, which led to multiple differentials in the working diagnosis. A CT showed the mass to have a delayed enhancement. Surgical exploration revealed a partially ruptured hydatid cyst with daughter cysts in the abdominal cavity and a solid-component mass lesion. We proceeded with a right partial hepatectomy. Pathological evaluation revealed a pale mass lesion with a large collapsed cyst. HCC with unusual dense fibrillar fibrosis and cystic interface with normal parenchyma was observed. This case connects the multimodal assessment of radiology, surgery and pathology.

This is a case of a young woman who developed neurological and psychiatric symptoms 3 days after resection of an immature teratoma. She was diagnosed with anti-NMDA receptor encephalitis via positive serum antibody titres, which was later confirmed with cerebrospinal fluid antibody titres. Given her cancer diagnosis, she underwent treatment with bleomycin, etoposide and cisplatin chemotherapy in addition to 5 days of high-dose steroids (1 g of intravenous methylprednisolone) for the encephalitis. This treatment regimen led to significant clinical improvement 3 weeks after completion of one cycle of chemotherapy.

Current literature suggests an increased risk of venous thromboembolism (VTE) in people living with HIV (PLWH) with poorly controlled viraemia and immunodeficiency. VTE treatment guidelines do not specifically address anticoagulation management in PLWH. We report a case of a 33-year-old woman diagnosed with an unprovoked pulmonary embolism (PE) and deemed protein S deficient. Three years later, she was diagnosed with AIDS. Antiretroviral therapy (ART) was promptly initiated with viral suppression and immune reconstitution within 12 months. Eight years after her initial PE, the patient self-discontinued warfarin. Multiple repeat protein S values were normal. ART without anticoagulation has continued for 3 years with no thrombotic events. This case describes a patient with VTE presumably secondary to undiagnosed HIV with possible consequent acquired protein S deficiency. Additional research is needed to understand the characteristics of PLWH with VTE who may warrant long-term anticoagulation as opposed to shorter courses.

Disseminated histoplasmosis is a life-threatening condition in immunocompromised patients. The majority of healthy persons have benign disease not requiring treatment. However, in persons living with HIV, mortality is high and accurate diagnosis is paramount. We present a case of a 48-year-old HIV-positive woman who presented with haematuria and flank pain. She had a history of recurrent urinary tract infection and nephrolithiasis with obstructive hydronephrosis. During cystoscopy, a bladder lesion was found. Pathological evaluation demonstrated abundant intracellular organisms with apparent budding. Subsequent urine histoplasma antigen was negative. Given the high index of suspicion for histoplasmosis based on the surgical pathology findings and epidemiological history, the patient was started immediately on antifungal therapy. One week later, PCR results of the bladder lesion confirmed the presence of Histoplasma capsulatum. This case highlights a rare presentation of genitourinary histoplasmosis and the utility of surgical pathology evaluation and PCR for diagnosis.

We present a case of a 51-year-old immunosuppressed man with underlying chronic lymphoproliferative leukaemia (CLL), who presented to us in emergency with breathlessness, hydrophobia, anxiety and restlessness. He had a history of category 3 dog bite 2 months ago and had received a full course of rabies immunoglobulin and antirabies vaccine (ARV) as per the national schedule. As there were frank clinical reports of rabies, the patient was managed according to Milwaukee regimen. The patients died within a week of the appearance of symptoms. The brain autopsy revealed Negri bodies conforming the mortality due to rabies.Immunosuppressed patients, like our patient who had CLL have low antibody formation after rabies prophylaxis. Antibody titres in immunosuppressed patients need to be measured after the 2–4 weeks of the last injection of ARV to decide whether a booster of ARV needs to be administered or not.

PURPOSE Immunohistochemistry (IHC) is a newer technique for assessing the estrogen receptor (ER) status of breast cancers, with the potential to overcome many of the shortcomings associated with the traditional ligand-binding assay (LBA). The purpose of this study was to evaluate the ability of ER status determination by IHC, compared with LBA, to predict clinical outcome—especially response to adjuvant endocrine therapy—in a large number of patients with long-term clinical follow-up. PATIENTS AND METHODS ER status was evaluated in 1,982 primary breast cancers by IHC on formalin-fixed paraffin-embedded tissue sections, using antibody 6F11 and standard methodology. Slides were scored on a scale representing the estimated proportion and intensity of positive-staining tumor cells (range, 0 to 8). Results were compared with ER values obtained by the LBA in the same tumors and to clinical outcome. RESULTS An IHC score of greater than 2 (corresponding to as few as 1% to 10% weakly positive cells) was used to define ER positivity on the basis of a univariate cut-point analysis of all possible scores and disease-free survival (DFS) in patients receiving any adjuvant endocrine therapy. Using this definition, 71% of all tumors were determined to be ER-positive by IHC, and the level of agreement with the LBA was 86%. In multivariate analyses of patients receiving adjuvant endocrine therapy alone, ER status determined by IHC was better than that determined by the LBA at predicting improved DFS (hazard ratios/ P = 0.474/.0008 and 0.707/.3214, respectively) and equivalent at predicting overall survival (0.379/.0001 and 0.381/.0003, respectively). CONCLUSION IHC is superior to the LBA for assessing ER status in primary breast cancer because it is easier, safer, and less expensive, and has an equivalent or better ability to predict response to adjuvant endocrine therapy.

A 23-year-old man with a history of migraine and focal seizures, developed painless visual loss in the left eye associated with optic disk edema. There was no recent history of cat exposure except for a cat that lives outside. Initial laboratory studies were negative. magnetic resonance imaging brain and orbits without and with fat suppression and intravenous contrast was normal. The patient admitted to routinely skinning, processing and consuming deer while not wearing gloves, and he also frequently had cuts on his hands while doing so. The serum Toxoplasma gondii IgG antibody returned at400 (0-7.1 IU/mL) with the IgM at 10.4 (0-7.9 AU/mL).

Anaemia is a common complication of chronic kidney disease. The most important contributory factor is an abnormally low circulating concentration of erythropoietin, which is produced by the kidney peritubular cells. Anaemia of kidney disease is likely to develop once the glomerular filtration rate (GFR) is

Background: Methadone maintenance treatment (MMT) is an effective treatment for opioid use disorder. However, subtherapeutic dosing may lead to continued opioid use by failing to suppress opioid withdrawal and craving. Preclinical and pilot experimental research suggests that cannabinoids may reduce opioid withdrawal and craving. We sought to test whether the association between low methadone dose and illicit opioid use differs according to concurrent cannabis use patterns. Methods: Data for this study were derived from two community-recruited cohorts of people (≥18 years old) who use illicit drugs in Vancouver, Canada. We used generalized estimating equations to estimate the adjusted association between lower daily MMT dose (

Introduction: Cannabis products containing delta-8-THC became widely available in most of the United States in late 2020 and rapidly became a significant source of revenue for hemp processing companies, especially in states where use of delta-9-THC remains illegal or requires professional authorization for medical use. Scientific research on the use of delta-8-THC is scarce, previous clinical studies included a combined total of 14 participants, leading some state governments to prohibit it until its properties and effects are better understood. Methods: Researchers developed an online survey for delta-8-THC consumers addressing a broad range of issues regarding delta-8-THC, including use for the treatment of health and medical conditions. Previous survey studies on the medical use of cannabis and cannabis products informed survey components. Results: Patterns of delta-8-THC use had both similarities with and differences from the use of delta-9-THC cannabis and products. Administration methods were primarily edibles (64%) and vaping concentrates (48%). About half of the participants (51%) used delta-8-THC to treat a range of health and medical conditions, primarily anxiety or panic attacks (69%), stress (52%), depression or bipolar disorder (46%), and chronic pain (41%). Participants compared delta-8-THC very favorably with both delta-9-THC and pharmaceutical drugs and reported substantial levels of substitution for both. Most participants did not inform their primary care provider of their delta-8-THC use (78%) and were not confident of their primary care provider's ability to integrate medical cannabis into their treatment (70%). Knowledge of effective dosages was low, and participants' knowledge of delta-8-THC was primarily from the Internet and their own experiences. Conclusion: Harm reduction is a central component of public health. Although the legal environment is becoming more restrictive for delta-8-THC in comparison to delta-9-THC, results suggest that delta-8-THC may be equally effective for desired purposes of cannabis use and lower in undesirable or adverse effects. All policies and practices should be informed by empirical evidence. Considerable research will be needed to systematically verify the patterns reported by participants, and collaborations among academic researchers, government, and the cannabis industry may be valuable in developing the knowledge base for delta-8-THC and other cannabinoids.

Patients with angiotensin-converting enzyme inhibitor (ACEI)-induced angioedema (ACEIIA) may visit family physicians. The aim of this article was to describe a case of delayed-onset ACEIIA and to present a concise scoping review. Using a case report and a scoping review study design, we report a case of ACEIIA, with clinically confirmed diagnosis. The symptoms resolved after replacing the offending ACEI with another antihypertensive agent. After excluding other causes of perioral swelling and discontinuation of ACEI, the patient was symptom-free within a few days thereafter. Based on this case presentation, we performed a meta-narrative scoping review including up-todate diagnosis and management of ACEIIA, based on published data in English, French, and German from inception to April 1, 2021. Patients with angioedema of unknown origin should be cautiously examined to rule out oral diseases, including allergy to dental materials and drug-induced angioedema. Clinicopathological aspects and current treatment guidelines for ACEI-associated angioedema are also presented.

Background The rs1344706 single nucleotide polymorphism in the ZNF804A gene has been associated with risk for psychosis in multiple genome-wide association studies, yet mechanisms underlying this association are not known. Given preclinical work suggesting an impact of ZNF804A on dopamine receptor gene transcription and clinical studies establishing dopaminergic dysfunction in patients with schizophrenia, we hypothesized that the ZNF804A risk single nucleotide polymorphism would be associated with variation in dopamine receptor availability in the human brain. Methods In this study, 72 healthy individuals genotyped for rs1344706 completed both [18F]fallypride and [11C]NNC-112 positron emission tomography scans to measure D2/D3 and D1 receptor availability, respectively. Genetic effects on estimates of binding potential for each ligand were tested first with canonical subject-specific striatal regions of interest analyses, followed by exploratory whole-brain voxelwise analyses to test for more localized striatal signals and for extrastriatal effects. Results Region of interest analyses revealed significantly less D2/D3 receptor availability in risk-allele homozygotes (TT) compared with non-risk allele carriers (G-allele carrier group: TG and GG) in the associative striatum and sensorimotor striatum, but no significant differences in striatal D1 receptor availability. Conclusions These data suggest that ZNF804A genotype may be meaningfully linked to dopaminergic function in the human brain. The results also may provide information to guide future studies of ZNF804A-related mechanisms of schizophrenia risk.

Introduction Advances in the development of drugs with novel mechanisms of action have not been sufficient to significantly reduce the percentage of patients presenting drug-resistant epilepsy. This lack of satisfactory clinical results has led to the search for more effective treatment alternatives with new mechanisms of action. Development The aim of this study is to examine epidemiological aspects of the use of cannabis-based products for the treatment of epilepsy, with particular emphasis on the main mechanisms of action, indications for use, clinical efficacy, and safety. We conducted a narrative review of articles gathered from the PubMed, EMBASE, and Google Scholar databases and from the reference sections of relevant publications. Conclusions In recent years there has been growing interest in the use of cannabis-based products for the treatment of a wide range of diseases, including epilepsy. The cannabis plant is currently known to contain more than 100 terpenophenolic compounds, known as cannabinoids. The 2 most abundant are delta-9-tetrahydrocannabinol and cannabidiol. Studies of preclinical models of epilepsy have shown that these cannabinoids have anticonvulsant properties, and 100% purified cannabidiol and cannabidiol-enriched cannabis extracts are now being used to treat epilepsy in humans. Several open-label studies and randomised controlled clinical trials have demonstrated the efficacy and safety of these products.

Introduction During pregnancy, women are at an increased risk of developing iron-deficiency anemia. Objective The objective of this study was to assess the diagnostic performance of the reticulocyte hemoglobin equivalent (RET-He) in the early detection of iron-deficiency anemia in a group of pregnant women and to establish a reference range for this parameter in a group of control individuals. Method: A total of 60 patients and 130 control subjects were included in the study. Blood samples collected from the subjects were submitted to a complete blood count and a serum ferritin test and the data were analyzed by comparing the groups and ROC curves. Results The reference range found for the RET-He was between 29.75pg and 38.24pg, with a median of 35pg. The receiver operating characteristic (ROC) curve analysis for the ferritin parameter showed an area under the curve of 0.732 for the RET-He, 0.586 for hemoglobin, 0.551 for the mean corpuscular hemoglobin concentration and 0.482 for the mean corpuscular volume. Conclusion Early diagnosis of iron deficiency anemia in pregnancy is essential to prevent damage to both maternal and fetal health. The RET-He presents an excellent potential as an auxiliary tool for the diagnosis of iron deficiency in pregnant women.

Neurological paraneoplastic syndrome is a relatively rare condition in patients with malignant tumors. Recently, it has been reported that anti-Aquaporin 4 (AQP4) antibody is highly specific for neuromyelitis optica. The patient was a 76-year-old man. He underwent right upper lobectomy for squamous cell carcinoma of the lung. Although the immediate postoperative course was uneventful, neurological symptoms became apparent from postoperative day (POD) 4. Magnetic resonance imaging showed longitudinally extended edematous lesions in the spinal cord, and a cerebrospinal fluid examination was positive for anti-AQP4 antibody, leading to the diagnosis of paraneoplastic neuromyelitis optica. Despite multiple rounds of steroid pulse therapy and plasma exchange, the neurological symptoms worsened and the patient died on POD 46. The development of neuromyelitis optica in the early postoperative period could be related to the influence of surgical stress or epidural anesthesia.

Helicobacter pylori (H. pylori) is a spiral microorganism considered as a gram-negative, this organism colonize the microenvironment of gastric for more than 50% of world population. The present study involved 78 patients, 39 of them had a clinical diagnosis of gastric ulcer and the remaining 39 had a clinical diagnosis of gastric cancer. Biopsies were taken from December 2018” until the end of July 2019 and the patients were between 25 and 60 years old. The initial diagnosis of H. pylori was performed by the rapid urease test (RUT). The samples also have been tested for IL-17 gene expression by immunihistochemical techniques. All the samples have been investigated for UreA gene, and the results showed the H.pylori positive in 32 (82%) samples and it was negative in 7 (18%) samples in gastric cancer, whereas the gastric ulcer group showed 29 (75%) negative samples and 10 (25%) positive for H.pylori. Furthermore, the sequencing result of gastric cancer group showed 95% compatibility, while gastric ulcer patients showed 98% compatibility with NCBI. The phylogenetic analysis exhibited the genetic dimension among the samples and the world was 96% and 99% compatibility values.

The advent of immunotherapy has revolutionised the treatment of metastatic lung cancer and it has recently been established as the standard of care in the radical treatment of lung cancer. However, immune-related adverse events (IrAEs) frequently occur in patients treated with immunotherapy, and rare IrAEs continue to be identified. We report a case of immunotherapy-induced coeliac disease due to adjuvant durvalumab post-chemoradiotherapy in a patient receiving curative treatment for lung cancer. The patient had raised anti-tissue transglutaminase IgA and histological findings consistent with coeliac disease. This is the first published case report of probable immunotherapy-induced coeliac disease both with the immunotherapy drug durvalumab and in the curative lung cancer setting.

Essential thrombocythaemia (ET) is a myeloproliferative neoplasm where there is a clonal proliferation of thrombocytes. Whilst most often diagnosed incidentally, it can uncommonly present with arterial thrombosis. This is a case presentation of a 36-year-old male who was diagnosed with ET following myocardial infarction caused by multiple thrombotic emboli. The patient was initially misdiagnosed with viral myopericarditis based on an atypical history of chest pain with a viral prodrome. Reattendance a month later with further chest pain, dynamically raised troponin and ECG changes raised suspicions of ACS. Analysis of blood markers from both admissions showed consistently elevated platelet counts. A CMR scan revealed focal ischaemic scars in multiple cardiac segments consistent with an acute coronary event or coronary embolisation. A subsequent coronary angiography demonstrated minimal coronary artery disease. JAK2 gene V617F mutation was detected, confirming ET. The patient was commenced on pegylated interferon-alpha and dual antiplatelet therapy, and discharged with follow-up.

Eight-and-a-half syndrome is a rare entity characterised by conjugate horizontal gaze palsy, ipsilateral internuclear ophthalmoplegia and ipsilateral lower motor neuron type facial palsy. It is due to a lesion affecting median longitudinal fasciculus, paramedian pontine reticular formation and facial nerve fascicle on the same side at the level of pons. The diagnosis is easily missed as it needs detailed ocular movement examination. It is mainly caused due to infarction or demyelinating conditions. We are reporting an interesting case of a 54-year-old man with right-side eight-and-a-half syndrome due to acute ischaemic stroke and ST-elevation myocardial infarction of the inferior wall.

Primary pneumomediastinum is the presence of air in the interstitium of the mediastinum. The exact aetiology is unclear; nevertheless, it has been reported more frequently in patients with asthma and in individuals who use recreational drugs. It is commonly preceded by a sharp rise in intrathoracic pressure as in a Valsalva-like manoeuvre. We describe a rare case of severe pneumomediastinum with a small pneumothorax related to cannabis smoking and aggravated by vigorous sexual intercourse. The patient was successfully treated conservatively due to clinical and radiological stability and the absence of secondary cause.

Background Allergic bronchopulmonary aspergillosis (ABPA) is an allergic reaction to colonisation of the lungs with the fungus Aspergillus fumigatus and affects around 10% of people with cystic fibrosis. ABPA is associated with an accelerated decline in lung function. High doses of corticosteroids are the main treatment for ABPA; although the long-term benefits are not clear, their many side effects are well-documented. A group of compounds, the azoles, have activity against Aspergillus fumigatus and have been proposed as an alternative treatment for ABPA. Of this group, itraconazole is the most active. A separate antifungal compound, amphotericin B, has been employed in aerosolised form to treat invasive infection with Aspergillus fumigatus, and may have potential for the treatment of ABPA. Antifungal therapy for ABPA in cystic fibrosis needs to be evaluated. This is an update of a previously published review. Objectives The review aimed to test the hypotheses that antifungal interventions for the treatment of ABPA in cystic fibrosis: 1. improve clinical status compared to placebo or standard therapy (no placebo); 2. do not have unacceptable adverse effects. If benefit was demonstrated, we aimed to assess the optimal type, duration and dose of antifungal therapy. Search methods We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings. In addition, pharmaceutical companies were approached. Date of the most recent search of the Group's Trials Register: 29 September 2016. Selection criteria Published or unpublished randomised controlled trials, where antifungal treatments have been compared to either placebo or no treatment, or where different doses of the same treatment have been used in the treatment of ABPA in people with cystic fibrosis. Data collection and analysis Four trials were identified by the searches; none of which was judged eligible for inclusion in the review. Main results No completed randomised controlled trials were included. Authors' conclusions At present, there are no randomised controlled trials to evaluate the use of antifungal therapies for the treatment of ABPA in people with cystic fibrosis, although trials in people who do not have cystic fibrosis have shown clinical and serological evidence of improvement and a reduction in the use of corticosteroids with no increase in adverse effects. Trials with clear outcome measures are needed to properly evaluate this potentially useful treatment for cystic fibrosis.

Background Gastric cancer is worldwide the fourth more common cancer type by incidence, and the third by mortality. We analyzed three missense variants of TAS2R38 gene: rs713598 (A49P), rs1726866 (V262A), and rs10246939 (I296V). These variants and their combination in haplotypes (proline, alanine and valine/tasters or alanine, valine and isoleucine/nontasters) and diplotypes are responsible for individual differences in bitter perception. The single-nucleotide polymorphisms and the related phenotypes are known to be associated with susceptibility to Gram-negative bacterial infections, such as Helicobacter pylori, and with risk of various cancer types. An association between intermediate tasters (as defined by TAS2R38 diplotypes) and increased risk of gastric cancer was reported in a Korean population. Methods We analyzed 2616 individuals of Latin American origin, representing the whole spectrum of lesions from gastritis to gastric cancer. Results Comparing cancer cases vs. noncancers we observed a decrease in risk associated with heterozygous carriers of rs10246939 (P = 0.006) and rs1726866 (P = 0.003) when compared with homozygotes of the more common allele. Also, the analysis of diplotypes/phenotypes reflected the same association, with super-tasters showing a borderline increased risk of developing gastric cancer compared to medium-tasters [odds ratio (OR) = 1.63; 95% confidence interval (CI), 1.04-2.56; P = 0.033]. Also, nontasters showed an increased risk when compared to medium-tasters although not reaching statistical significance (OR = 1.58; 95% CI, 0.80-2.87; P = 0.203). We also tested the interactions between the TAS2R38 genotypes and H. pylori cagA status in a subset of samples and found no interaction. Conclusion In conclusion, our results suggest only a modest contribution of TAS2R38 gene genetic variability in gastric cancer etiology.

We present a case of a 7-year-old Afro-Caribbean girl presenting with rapidly progressive bilateral sensorineural hearing loss. She was found to have an elevated Angiotensin converting enzyme (ACE) and mediastinal lymphadenopathy containing non-caseating granulomas with multinucleate giant cells, in keeping with sarcoidosis. Cranial imaging demonstrated labyrinthitis. She underwent urgent bilateral cochlear implantation with rehabilitation of hearing sufficient to restart education within 1 month.

Vancomycin is a widely used antibiotic and rarely can cause drug-induced thrombocytopenia. A patient with hospital-acquired meningitis after neurosurgery was treated with systemic and intrathecal vancomycin. On 9th day of antibiotic treatment, the patient’s platelets dropped to 0.68×109/L. Multiple platelet transfusions had minimal influence on platelet count. After cessation of vancomycin therapy, platelets returned to normal values without any additional interventions. Diagnosis of vancomycin-induced thrombocytopenia was confirmed by detection of drug-dependent antiplatelet IgG antibodies.

Introduction: Cannabis use is common in the setting of inflammatory bowel disease (IBD). Patients frequently use cannabis to treat IBD-associated symptoms, and there is evidence that cannabis and its derivatives are helpful for this purpose. However, it is unclear how the symptom profiles of active IBD cannabis users and nonusers compare and how these symptoms may relate to their underlying disease state and/or complications. Materials and Methods: We performed a retrospective cohort study using a consented IBD natural history registry from a single tertiary care referral center between January 1, 2015 and August 31, 2020. We asked patients about current cannabis use and frequency. We also abstracted demographic and clinical characteristic information, including endoscopic severity, and totals and subscores of surveys assessing IBD characteristics, presence of anxiety/depression, and IBD-associated symptoms. We compared clinical and demographic factors of cannabis users and nonusers and developed a logistic regression model to evaluate for independent associations with cannabis use. Results: Three hundred eighty-three IBD patients met the inclusion criteria (206 females, 177 males; 258 Crohn's disease [CD], 118 ulcerative colitis, and 7 indeterminate colitis). Thirty patients (7.8%) were active cannabis users, consuming it for an average of 2.7 times per week. Cannabis users were more likely to report abdominal pain (83.3% vs. 61.7%), gas (66.7% vs. 45.6%), tenesmus (70.0% vs. 47.6%), and arthralgias (53.3% vs. 20.3%) compared to those that did not use cannabis (p

Objective: The objective of this study was to evaluate the safety and efficacy of medications commonly used in autism spectrum disorder (ASD) and compare this to what current research has shown regarding medical cannabis use in this population. Methods: Searches were performed to collect information surrounding currently used medications and their safety and efficacy profiles, biologic plausibility of cannabis use for symptoms of ASD, and studies detailing cannabis' safety and efficacy profile for use in the ASD population. Results were used to compare medications to cannabis as a proposed treatment. Results: The heterogeneity of ASD produces great difficulties in finding appropriate treatment, leading to many medication changes or treatment trials throughout a patient's life. Commonly prescribed medications display varying levels of efficacy, safety, and tolerability between patients and symptoms targeted. Some of the most common side effects cited are also considered the most troubling symptoms associated with ASD; aggression, anxiety, irritability, and a negative effect on cognition, leading many patients to discontinue use as the side effects outweigh benefits. Recent case reports and retrospective studies have displayed the potential efficacy, safety, and tolerability of cannabidiol (CBD)-rich medical cannabis use for treating both core symptoms of ASD and many comorbid symptoms such as irritability and sleep problems. Studies have also identified circulating endocannabinoids as a possible biomarker for ASD, providing another possible method of diagnosis. Conclusions: Currently, there are no approved medications for the core symptoms of ASD and only two medications Food and Drug Administration approved for associated irritability. Prescribed medications for symptoms associated with ASD display varying levels of efficacy, safety, and tolerability among the heterogeneous ASD population. At the time of this study there are no published placebo-controlled trials of medical cannabis for ASD and the observational studies have limitations. CBD-rich medical cannabis seems to be an effective, tolerable, and relatively safe option for many symptoms associated with ASD, however, the long-term safety is unknown at this time.

Chronic cavitary pulmonary aspergillosis (CCPA) is a slow destructive type of chronic pulmonary aspergillosis, characterised by multiple pulmonary cavities that develop and expand over several months or years. Pleural involvement in the form of pneumothorax has been rarely reported in CCPA. We report such an unusual case of an immunocompromised male, with a history of chronic cough and fever, presenting with acute onset of shortness of breath. Chest imaging showed bilateral multiple cavitating nodules, ground glass opacities and dense right middle lobe consolidations and right-sided pneumothorax. Bronchoalveolar lavage (BAL) showed septate hyaline hyphae on KOH (potassium hydroxide) staining and fungal culture grew Aspergillus fumigatus. BAL and serum galactomanan were positive and serum IgG for A. fumigatus was 58 MgA/L (0–40MgA/L) confirming the cause of spontaneous secondary pneumothorax in our patient as CCPA.

A 42 year-old Caribbean woman with, known type 2 diabetes, was admitted with worsening fatigue, arthritis and rashes. She was diagnosed with multisystem systemic lupus erythematosus and was initially treated with systemic steroids. During this admission, she had persistently elevated capillary glucose levels with insulin requirements over 8 U/kg/day that still did not control her blood glucose levels. Due to her profound hyperglycaemia, serum samples of fasting insulin, C-peptide, paired with blood glucose were analysed, which confirmed significant hyperinsulinaemia. Further analysis confirmed the presence of insulin receptor antibodies consistent with type B insulin resistance.She was started on intravenous cyclophosphamide (Euro-Lupus regimen) along with continuous glucose monitoring system. After completing her six cycles of cyclophosphamide, she no longer required insulin treatment. The goal of therapy for our patient with confirmed type B insulin resistance was to manage hyperglycaemia with high doses of insulin until autoantibodies were eliminated with immunosuppressive therapy.

Infection is a serious adverse event limiting left ventricular assist device (LVAD) therapy in advanced heart failure patients, but a reliable means to identify patients at increased risk of infection is still lacking. We hypothesized that preoperative elevated levels of plasma Oncostatin M (OSM), a cytokine marker of leukocyte activation and inflammation, would be predictive of subsequent infection. We measured plasma OSM in 41 LVAD patients one day before LVAD implantation and postoperatively over two months. Preoperative plasma OSM levels were normal in 27 patients (group A, 4.9 ± 3.2 pg/ml) but elevated in 14 patients (group B, 1649.0 ± 458.9 pg/ml) ( p = 0.003). Early postoperative levels rose in both groups and declined rapidly in group A, with group B declining slowly over two months. Significantly more infections developed in group B than group A patients over two months postimplantation ( p = 0.004). No other routine clinical assessment or laboratory testing afforded this differentiation. These findings suggest that preoperative plasma OSM levels may assist in identifying patients at increased risk of infections after LVAD implantation.

We report a case of vancomycin-induced thrombocytopenia (VIT) with rapid onset after re-exposure to vancomycin. A 58-year-old man with cellulitis was initiated on vancomycin. Approximately 1 hour into the vancomycin infusion, the patient developed an infusion-related reaction. Vancomycin infusion was stopped. A complete blood count obtained 4 hours after discontinuation of the vancomycin infusion revealed a platelet count of 31 ×10­9/L. Investigations ruled out likely causes of thrombocytopenia. VIT was diagnosed based on clinical symptoms and confirmed with drug-dependent platelet antibody testing. Without complications, platelet counts recovered within 7 days after discontinuation of vancomycin. No correlation between vancomycin level and VIT was observed.

The fibronectin type III domain containing 5 (FNDC5)/Irisin, a novel energy-regulating hormone, is associated with lipid and carbohydrate metabolism. It is produced in low amounts by normal hepatic tissue, while in human hepatocellular carcinoma (HCC), in which aberrant de novo lipogenesis (DNL) occurs, the hepatic expression of FNDC5/Irisin is still unknown. The gene expression of FNDC5/Irisin, associated to key regulators of DNL, inflammation and cancer progression was evaluated in liver tissue of 18 patients with HCC undergoing liver transplantation and of 18 deceased donors. Hepatic mRNA expression of FNDC5/Irisin and stearoyl-CoA desaturase (SCD-1), main enzymatic regulator of DNL, were significantly higher in HCC patients than in donors (p, This pre-print version may be used for non-commercial purposes in accordance with CC BY-NC-ND license terms and conditions.

A 49-year-old female emergency room nurse presented with painless papular rash that started on both arms and legs and spread to her palms and soles ([figure 1][1]). She also endorsed fatigue, low-grade fever and transient arthralgia. She was sent home on topical steroids, which improved her pruritus

We describe a case of a 42-year-old man who presented with anginal chest pain. He had objective evidence of ongoing cardiac injury. After initial treatment for coronary arterial disease, cardiac catheterisation revealed diffuse coronary arterial thrombosis with embolisation. Follow-up testing implicated new-onset antiphospholipid antibody syndrome as the aetiology.

Posterior reversible encephalopathy syndrome (PRES) is characterised by headache, altered mental status, seizures and visual loss that resolve spontaneously in a short span of time. The typical radiographic findings include symmetrical hyper intensities in Magnetic Resonance Fluid Attenuated

We reported a case of gnathostomiasis in a 42-year-old woman with an unclear history of eating high-risk foods and had a non-migratory skin lesion, negative serological testing and normal blood eosinophil counts. A diagnosis of gnathostomiasis was based on a live, third-stage Gnathostoma spinigerum larva that was randomly taken from the patient’s skin lesion by herself. The presenting case report demonstrates challenges in correctly diagnose cutaneous gnathostomiasis even in endemic countries due to atypical skin lesions, negative serology testing and the absence of eosinophilia and thus, the widely used classic triad of suggestive evidence of gnathostomiasis is not fulfilled.

We describe antiglomerular basement membrane (anti-GBM) disease with rapidly progressive glomerulonephritis and concurrent parainfluenza pneumonia. Circulating anti-GBM antibodies were barely detectable and disappeared rapidly following corticosteroids, cyclophosphamide and plasma exchange. Kidney biopsy demonstrated strong linear GBM staining for IgG and IgG4 and unusually prominent endocapillary hypercellularity, suggesting ‘atypical anti-GBM disease’, although glomerular necrosis and crescents were also seen. When kidney function deteriorated further, despite persistently absent circulating anti-GBM antibodies, a repeat kidney biopsy was performed, showing crescents in 100% of glomeruli with ongoing endocapillary hypercellularity and strong IgG and IgG4 GBM staining. This case highlights complexities in the diagnosis of anti-GBM disease, with clinical and histological features bridging the atypical to typical anti-GBM disease spectrum. We hypothesise that these findings might be explained by the presence of IgG4 (rather than traditional IgG1 or IgG3) autoantibodies. To our knowledge, this is also the first report of parainfluenza associated with anti-GBM disease.

Morgagni hernia is the rarest type of congenital diaphragmatic hernia, which can present late in adulthood. Here, we report a case of Morgagni hernia in an elderly woman who presented as an acute coronary syndrome with raised troponin level. X-ray of the chest (CXR) showed air–fluid level in the right lower hemithorax with loss of right diaphragmatic outline and subsequently confirmed strangulated Morgagni hernia with CT. She was treated with emergency laparotomy to reduce the hernia content and surgical repair with mesh done. In conclusion, Troponin can be falsely positive in Morgagni hernia patients, possibly due to strain on the heart by herniated bowel contents. Basic imaging such as a (CXR) is useful in the case of chest pain to rule out the non-cardiac causes. Although ‘time is the myocardium’ in the setting of all cases of chest pain with raised troponin, CXR should be done before treatment that poses bleeding risk and unnecessary delay in laparotomy.

PURPOSE: To describe the incidence, prevalence, and clinical characteristics of presumed ocular histoplasmosis syndrome (POHS) in a Histoplasma endemic region. METHODS: The International Classification of Diseases, 9(th) and 10(th) Revision codes were used to search the Rochester Epidemiology Project, a record-linkage system for medical care provided in Olmsted County, MN. Medical records were reviewed to confirm POHS diagnoses in county residents from January 1, 2006 to December 31, 2015. Age- and sex-adjusted incidence rates were calculated and adjusted to the 2010 U.S. White population. RESULTS: There were 18 incident cases (30 eyes) and 87 prevalent cases (131 eyes). The incidence rate was 1.35 per 100,000 per year. The mid-study prevalence rate was 0.064%. Choroidal neovascularization (CNV) occurred in 17.4% of affected eyes. At last follow-up, 16.8% of affected eyes had POHS-related decreased VA (

The ability to distinguish endometrial serous carcinoma (SC) from high-grade endometrioid adenocarcinoma is of great importance given their differences in prognosis and management. In practice, this distinction typically relies upon the use of a focused immunohistochemical panel including p53, p16, and mismatch repair proteins. The expression of p16 is characteristically strong and diffuse in SCs, and weak and/or patchy in many high-grade endometrioid adenocarcinomas. Here, we report a subset of SCs that are entirely negative for p16 immunostaining, a pattern we refer to as "p16 null." This pattern was identified in 2 of 63 cases of SC diagnosed at our institution-1 with histologically classic features and 1 with ambiguous high-grade histologic features. These tumors otherwise showed a SC signature by immunohistochemical and demonstrated an SC pattern of genetic mutations. No mutation in the gene for p16, cyclin-dependent kinase inhibitor 2A (CDKN2A), was identified in either case. However, molecular correlates for the absent p16 expression were present, including homozygous deletion of CDKN2A in one case and hemizygous deletion of CDKN2A with promotor hypermethylation of the remaining allele in the other case. To our knowledge, this constitutes the first report conclusively demonstrating the existence of a small subset of SCs that are completely negative by p16 immunohistochemistry, and the molecular lesions responsible for this pattern. In the context of an otherwise clinically and histologically classic example of SC, we endorse this "null" p16 staining pattern as an alternative aberrant staining pattern that should not deter one from committing to this diagnosis.

Congenital factor V (FV) deficiency is a rare hemorrhagic disorder that can cause excessive bleeding during and after surgery in the affected patient. This report is the case of a patient who had FV deficiency with recurrent posthemorrhoidectomy bleeding treated with the hemostatic procedure and fresh frozen plasma (FFP) transfusions. A 45-year-old male patient had previously undergone hemorrhoidectomy for multiple hemorrhoids at a local hospital. Hemorrhoidectomy was successful; however, he was transferred to our hospital for evaluation of the origin of the recurrent posthemorrhoidectomy bleeding and underwent a hemostatic procedure. This bleeding was treated with coagulation using electrocautery, multiple sutures, and FFP transfusion (1,600 mL/day) for 7 consecutive days. The patient’s plasma FV activity was 23%. Early detection of clotting factor deficiency in patients with hemorrhagic events after surgical treatments may prevent unnecessary procedures such as reoperations and minimize the cost of replacement therapy such as large-volume FFP transfusion.

Background: Men over the age of 40 are more likely to develop benign prostatic hyperplasia (BPH). BPH is characterized by proliferation of the prostatic epithelium and stroma. Selenium nanoparticles (SeNPs), is an essential metalloid mineral and antioxidant. In this study, SeNPs were tested for their potential protective and curative impacts on BPH in rats. Materials and methods: 50 male Sprague-Dawley rats were randomly divided into five groups: Group I (Control group); Group II (Orchiectomized group): bilateral orchiectomy was conducted on rats; Group III (BPH group): testosterone (TE) enanthate injection was used to induce BPH; Group IV (Protective group): rats were given SeNP before subjecting rats to BPH; Group V (Curative group): rats were succumbed to BPH, followed by administration of SeNP. Measurement of prostate specific antigen (PSA) and TE in serum was performed and prostates were weighed and prepared for histological, immunohistochemical and ultrastructural examination. Results: In the BPH group, serum TE- and PSA-levels, as well as prostate weight, increased significantly and significant decreases in the protective and curative groups. Reduced acinar lumen, expansion of stroma and epithelial hyperplasia were noticed in the BPH group, which were ameliorated significantly both in protective and curative groups. There was an increase in PCNA immunoreaction in the BPH group and a decrease in both the protective and curative groups. On TEM of BPH group, the nuclei appeared irregular with dilated endoplasmic reticulum, loss of cell boundaries and apical microvilli. The protective group showed more improvement than the curative group. Conclusions: The effects of SeNPs on BPH induced by TE in rats, were both protective and curative, although the protective effects were more pronounced.

BACKGROUND Burkholderia cepacia complex (BCC) represents a group of multidrug-resistant gram-negative bacteria that cause infections among immunocompromised hosts. Bacteremia occurs in patients who are chronically ill and is associated with substantial morbidity and mortality. The aim of this study was to investigate the clinical characteristics and outcomes of BCC bacteremic patients without cystic fibrosis. METHODS We conducted a retrospective study at the National Taiwan University Hospital. Adults with BCC bacteremia from January 2015 to May 2019 were enrolled. The primary outcome was 14-day mortality. Multivariable logistic regression was performed for outcome analysis. RESULTS One-hundred and ninety-five patients were analyzed and their mean age was 67 years. Over 95% of the BCC isolates were susceptible to trimethoprim/sulfomethoxazole (TMP/SXT). Levofloxacin resistance rates were high, with only 25.1% of isolates being susceptible. Pairwise comparisons were made between different definitive regimens including meropenem-monotherapy, ceftazidime-monotherapy, levofloxacin-monotherapy, TMP/SXT-monotherapy, tigecycline-monotherapy as well as combination versus monotherapy. No regimen was significantly associated with survival in our study. Multivariable logistic regression showed that the Pitt bacteremia score (adjust odds ratio [aOR],1.46; 95% confidence interval [CI],1.19-1.79; p

OBJECTIVES Neonatal rodents and piglets naturally regenerate the injured heart after myocardial infarction. We hypothesized that neonatal rabbits also exhibit natural heart regeneration after myocardial infarction. METHODS New Zealand white rabbit kits underwent sham surgery or left coronary ligation on postnatal day 1 (n = 94), postnatal day 4 (n = 11), or postnatal day 7 (n = 52). Hearts were explanted 1 day postsurgery to confirm ischemic injury, at 1 week postsurgery to assess cardiomyocyte proliferation, and at 3 weeks postsurgery to assess left ventricular ejection fraction and scar size. Data are presented as mean ± standard deviation. RESULTS Size of ischemic injury as a percentage of left ventricular area was similar after myocardial infarction on postnatal day 1 versus on postnatal day 7 (42.3% ± 5.4% vs 42.3% ± 4.7%, P = .9984). Echocardiography confirmed severely reduced ejection fraction at 1 day after postnatal day 1 myocardial infarction (33.7% ± 5.3% vs 65.2% ± 5.5% for postnatal day 1 sham, P = .0001), but no difference at 3 weeks after postnatal day 1 myocardial infarction (56.0% ± 4.0% vs 58.0% ± 3.3% for postnatal day 1 sham, P = .2198). Ejection fraction failed to recover after postnatal day 4 myocardial infarction (49.2% ± 1.8% vs 58.5% ± 5.8% for postnatal day 4 sham, P = .0109) and postnatal day 7 myocardial infarction (39.0% ± 7.8% vs 60.2% ± 5.0% for postnatal day 7 sham, P