Serous cystic neoplasm of the pancreas: a multinational study of 2622 patients under the auspices of the International Association of Pancreatology and European Pancreatic Club (European Study Group on Cystic Tumors of the Pancreas).

OBJECTIVES: Serous cystic neoplasm (SCN) is a cystic neoplasm of the pancreas whose natural history is poorly known. The purpose of the study was to attempt to describe the natural history of SCN, including the specific mortality. DESIGN: Retrospective multinational study including SCN diagnosed between 1990 and 2014. RESULTS: 2622 patients were included. Seventy-four per cent were women, and median age at diagnosis was 58 years (16-99). Patients presented with non-specific abdominal pain (27%), pancreaticobiliary symptoms (9%), diabetes mellitus (5%), other symptoms (4%) and/or were asymptomatic (61%). Fifty-two per cent of patients were operated on during the first year after diagnosis (median size: 40 mm (2-200)), 9% had resection beyond 1 year of follow-up (3 years (1-20), size at diagnosis: 25 mm (4-140)) and 39% had no surgery (3.6 years (1-23), 25.5 mm (1-200)). Surgical indications were (not exclusive) uncertain diagnosis (60%), symptoms (23%), size increase (12%), large size (6%) and adjacent organ compression (5%). In patients followed beyond 1 year (n=1271), size increased in 37% (growth rate: 4 mm/year), was stable in 57% and decreased in 6%. Three serous cystadenocarcinomas were recorded. Postoperative mortality was 0.6% (n=10), and SCN's related mortality was 0.1% (n=1). CONCLUSIONS: After a 3-year follow-up, clinical relevant symptoms occurred in a very small proportion of patients and size slowly increased in less than half. Surgical treatment should be proposed only for diagnosis remaining uncertain after complete workup, significant and related symptoms or exceptionally when exists concern with malignancy. This study supports an initial conservative management in the majority of patients with SCN. TRIAL REGISTRATION NUMBER: IRB 00006477.

Cryptococcosis and Cryptococcal Meningitis: A Narrative Review and the Up-to-Date Management Approach.

Cryptococcosis is a fungal infectious disease that enormously impacts human health worldwide. Cryptococcal meningitis is the most severe disease caused by the fungus Cryptococcus, and can lead to death, if left untreated. Many patients develop resistance and progress to death even after treatment. It requires a prolonged treatment course in people with AIDS. This narrative review provides an evidence-based summary of the current treatment modalities and future trial options, including newer ones, namely, 18B7, T-2307, VT-1598, AR12, manogepix, and miltefosine. This review also evaluated the management and empiric treatment of cryptococcus meningitis. The disease can easily evade diagnosis with subacute presentation. Despite the severity of the disease, treatment options for cryptococcosis remain limited, and more research is needed.

Air quality and mental illness: role of bioaerosols, causal mechanisms and research priorities.

BACKGROUND: Poor air quality can both trigger and aggravate lung and heart conditions, as well as affecting child development. It can even lead to neurological and mental health problems. However, the precise mechanisms by which air pollution affect human health are not well understood. AIMS: To promote interdisciplinary dialogue and better research based on a critical summary of evidence on air quality and health, with an emphasis on mental health, and to do so with a special focus on bioaerosols as a common but neglected air constituent. METHOD: A rapid narrative review and interdisciplinary expert consultation, as is recommended for a complex and rapidly changing field of research. RESULTS: The research methods used to assess exposures and outcomes vary across different fields of study, resulting in a disconnect in bioaerosol and health research. We make recommendations to enhance the evidence base by standardising measures of exposure to both particulate matter in general and bioaerosols specifically. We present methods for assessing mental health and ideal designs. There is less research on bioaerosols, and we provide specific ways of measuring exposure to these. We suggest research designs for investigating causal mechanisms as important intermediate steps before undertaking larger-scale and definitive studies. CONCLUSIONS: We propose methods for exposure and outcome measurement, as well as optimal research designs to inform the development of standards for undertaking and reporting research and for future policy.

In vivo electrophysiology of nigral and thalamic neurons in alpha-synuclein-overexpressing mice highlights differences from toxin-based models of parkinsonism.

Numerous studies have suggested that alpha-synuclein plays a prominent role in both familial and idiopathic Parkinson's disease (PD). Mice in which human alpha-synuclein is overexpressed (ASO) display progressive motor deficits and many nonmotor features of PD. However, it is unclear what in vivo pathophysiological mechanisms drive these motor deficits. It is also unknown whether previously proposed pathophysiological features (i.e., increased beta oscillations, bursting, and synchronization) described in toxin-based, nigrostriatal dopamine-depletion models are also present in ASO mice. To address these issues, we first confirmed that 5- to 6-mo-old ASO mice have robust motor dysfunction, despite the absence of significant nigrostriatal dopamine degeneration. In the same animals, we then recorded simultaneous single units and local field potentials (LFPs) in the substantia nigra pars reticulata (SNpr), the main basal ganglia output nucleus, and one of its main thalamic targets, the ventromedial nucleus, as well as LFPs in the primary motor cortex in anesthetized ASO mice and their age-matched, wild-type littermates. Neural activity was examined during slow wave activity and desynchronized cortical states, as previously described in 6-hydroxydopamine-lesioned rats. In contrast to toxin-based models, we found a small decrease, rather than an increase, in beta oscillations in the desynchronized state. Similarly, synchronized burst firing of nigral neurons observed in toxin-based models was not observed in ASO mice. Instead, we found more subtle changes in pauses of SNpr firing compared with wild-type control mice. Our results suggest that the pathophysiology underlying motor dysfunction in ASO mice is distinctly different from striatal dopamine-depletion models of parkinsonism.

Clinical Conundrum of Acute Hepatitis B With Concurrent Hepatitis E Infection Leading to Severe Acute Liver Injury.

Acute liver injury in the setting of acute fulminant hepatitis caused by the hepatitis B virus (HBV) can occur both during primary infection and after chronic HBV reactivation. Guidelines recommend considering antiviral therapy in both cases. Antiviral therapy with a nucleoside analog may be beneficial in patients with acute liver failure from acute HBV infection, though not all studies have shown a benefit. This is a case of a 53-year-old woman with a past medical history of untreated hepatitis C with undetectable viral load and right breast cancer status post lumpectomy, who presented to the emergency department with complaints of yellowish skin and sclera discoloration with right upper quadrant pain for one week. She was a known intravenous drug abuser and binge alcohol user. Her labs were positive for hepatitis B, hepatitis E, and hepatitis C viruses. She also had elevated liver enzymes with hyperbilirubinemia showing severe acute liver injury. Computed tomography of the abdomen and pelvis with contrast was normal, and the abdominal ultrasound showed homogenous echotexture of the liver without a focal lesion. The patient was diagnosed with acute fulminant hepatitis B. After initial hemodynamic stabilization, N-acetylcysteine (NAC) and tenofovir were started, and transaminases were followed. Liver function tests showed a downtrend, and, in a few weeks, they came to baseline. Hepatitis B viral load became undetectable as well. Acute hepatitis B infection is seldom treated. The presented case depicts the use of tenofovir in the setting of severe acute liver injury due to hepatitis B. Starting antiviral therapy (especially tenofovir disoproxil fumarate) early in the disease course was shown to have very assuring results with complete resolution of symptoms and normalization of liver function tests. The treatment protocol for acute HBV deserves further investigation.

Ceftriaxone-Induced Thrombotic Thrombocytopenic Purpura Treated Successfully With Plasmapheresis and Eculizumab: A Rare Case Report.

Thrombotic Thrombocytopenic Purpura (TTP) is a subtype of thrombotic microangiopathy (TMA) resulting in thrombocytopenia, anemia, fever, renal and neurological deficits. Although many drugs have been associated with drug-induced TTP, ceftriaxone has never been reported. Our case reports a patient who was started on ceftriaxone and developed TTP. Peripheral smear showed schistocytes and thrombocytopenia. Surprisingly, antibody formation against the metalloproteinase (ADAMTS13) levels were low-normal. The patient was treated with plasmapheresis and eczulimab, leading to platelet recovery and symptom resolution. TTP is a rare disorder and can be acquired or idiopathic. TTP can be diagnosed with normal ADAMTS13 as well. Further research is required to assess the mechanism by which ceftriaxone causes TTP. Physicians should consider the possibility of TTP in patients with similar presentations following ceftriaxone therapy and use it for timely diagnosis and treatment. Early diagnosis and treatment of ceftriaxone-induced TTP can prevent devastating consequences.

A Textbook Case of Human T-lymphotropic Virus-1 (HTLV-1)-Induced Adult T-cell Leukemia Treated With Cyclophosphamide, Hydroxydaunorubicin, Oncovin, and Prednisone/Prednisolone (CHOP).

Human T-lymphotropic virus-1 (HTLV-I) is an enveloped, single-stranded RNA virus of the Retroviridae family. The virus causes two well-recognized disease associations: adult T-cell leukemia/lymphoma (ATL) and HTLV-I-associated myelopathy (HAM), also known as tropical spastic paraparesis (TSP). We report a case of HTLV-1-induced adult T-cell lymphoma/leukemia in a 45-year-old female who presented with complaints of swelling on the right side of her neck and rash on her upper and lower extremities and abdomen. The patient also had a history of strongyloidiasis infection and Crohn's disease. She was found to have hypercalcemia and multiple lytic lesions of the bone found on the imaging. She also tested positive for HTLV-1 and T cell-positive for cluster of differentiation (CD) 2, CD3, partial CD5, and minimal CD56, later confirmed by the bone marrow (BM) and skin punch biopsies. ATL is characterized by the clonal proliferation of CD4+ T cells containing randomly integrated HTLV-I provirus, often associated with T-cell receptor gene rearrangements. ATL, in its aggressive forms, has one of the poorest prognoses of non-Hodgkin lymphoma. It is essential to raise awareness of ATL, although further research and trials are needed to solidify the treatment options to prevent mortality.

Necrotizing Autoimmune Myopathy: A Case Report on Statin-Induced Rhabdomyolysis.

Statin-induced necrotizing myopathy (SINM) is an uncommon but severe complication associated with statin medication. SINM can develop at any point after a person starts taking steroids. It is now being acknowledged as a component of the broader category of "statin-induced myopathy." Like other immune-mediated necrotizing muscle diseases, statin-induced myositis is identified by weakness in proximal muscles, increased serum creatine kinase (CK) levels, and, in some cases, dysphagia and respiratory distress. In addition, there is evidence of muscle cell damage when examined under a microscope, occurring with minimal or no infiltration of inflammatory cells. Diagnosing SINM promptly is frequently challenging due to its unpredictable development over time, with symptoms sometimes emerging many years after the initial exposure to statins. One distinctive characteristic of SINM is the continued presence of muscle inflammation and elevated CK levels even after discontinuing statin treatment. Currently, no clinical trials are available to guide how to manage statin-induced immune-mediated necrotizing myopathy (IMNM). Here, we present a case of a 42-year-old woman diagnosed with SINM and was found to have persistently elevated CPK despite discontinuation of statins. Our case also suggests that intravenous (IV) immunoglobins and steroids are an effective and well-tolerated alternative to immunosuppressants.

Fracture Resistance of Different Post-Core Systems: An In vitro Study.

Reasons for the failed endodontic teeth which had an extensive restoration can be attributed to the multiple materials that were used in it. Various post-core materials that are commonly used are compared for fracture resistance in the current study. Fourty maxillary incisors that needed root canal therapy were allocated into four groups of 10 each. Using adhesive resin cement, teeth were repaired in three experimental groups with ceramic fiber post, glass post, and stainless steel post. All these posts with composite post and core. Samples that still had their coronal structure were considered as controls that were without any post-cores. Every sample was ready for the best abutment preparation. Using the universal testing machine, all the specimens were examined for the compressive strength at 130° until fracture was experienced. The data for the force levels at which the fracture occurred were noted and compared for significance using analysis of variance (ANOVA), keeping P < 0.05 as significant. The fracture resistance values were significantly variable among all the groups, with P < 0.05. The stainless steel post exhibited the highest strength before it succumbed to the fracture. The glass posts showed better restorability and were esthetically acceptable. The least fracture resistance was demonstrated by teeth that had no post-core, highlighting the necessity of strengthening the tooth. Among all the experimental groups, the one that demonstrated the highest fracture resistance was composite core and steel posts.

Role of Fecal Microbiota Transplantation in Managing Clostridium Difficile Infection and Inflammatory Bowel Disease: A Narrative Review.

Fecal microbiota transplantation (FMT) has been emerging as an alternate treatment modality in the management of patients with dysbiosis by restoring abnormal gut microbiota composition through the transplantation of normal fecal microbiota from healthy donors. This technique has lately gained a lot of attention in the treatment of recurrent or refractory Clostridium difficile infection (CDI) owing to its high success rates combined with its favorable safety profile. FMT has also been attracting the interest of clinicians as a new treatment option for inflammatory bowel diseases (IBD). Here, we reviewed most of the recent advancements in the use of FMT for CDI as well as its use in the treatment of IBD.

Air quality and mental health: evidence, challenges and future directions.

BACKGROUND: Poor air quality is associated with poor health. Little attention is given to the complex array of environmental exposures and air pollutants that affect mental health during the life course. AIMS: We gather interdisciplinary expertise and knowledge across the air pollution and mental health fields. We seek to propose future research priorities and how to address them. METHOD: Through a rapid narrative review, we summarise the key scientific findings, knowledge gaps and methodological challenges. RESULTS: There is emerging evidence of associations between poor air quality, both indoors and outdoors, and poor mental health more generally, as well as specific mental disorders. Furthermore, pre-existing long-term conditions appear to deteriorate, requiring more healthcare. Evidence of critical periods for exposure among children and adolescents highlights the need for more longitudinal data as the basis of early preventive actions and policies. Particulate matter, including bioaerosols, are implicated, but form part of a complex exposome influenced by geography, deprivation, socioeconomic conditions and biological and individual vulnerabilities. Critical knowledge gaps need to be addressed to design interventions for mitigation and prevention, reflecting ever-changing sources of air pollution. The evidence base can inform and motivate multi-sector and interdisciplinary efforts of researchers, practitioners, policy makers, industry, community groups and campaigners to take informed action. CONCLUSIONS: There are knowledge gaps and a need for more research, for example, around bioaerosols exposure, indoor and outdoor pollution, urban design and impact on mental health over the life course.

Comparison of PapType to Digene Hybrid Capture 2, Roche linear array, and Amplicor for detection of high-risk human papillomavirus genotypes in women with previous abnormal pap smears.

PapType human papillomavirus (HPV) assay was compared to Hybrid Capture 2 (HC2), Amplicor (Amp), and Linear Array (LA) HPV tests in 894 women undergoing management for a high-grade Pap smear abnormality. The sensitivity in detection of underlying high-grade histological diagnosis by PapType was 90.3% and by HC2 was 79.8%, while by Amp and LA it was 92.4% and 91.6%, respectively. The specificities were 52.5%, 55.3%, 49.4%, and 51.7% for PapType, HC2, Amp, and LA, respectively.

Expression of glia maturation factor in neuropathological lesions of Alzheimer's disease.

AIMS: The pathology of Alzheimer's disease (AD) is characterized by the presence of amyloid plaques (APs), neurofibrillary tangles (NFTs), degenerating neurones, and an abundance of reactive astrocytes and microglia. We aim to examine the association between glia maturation factor (GMF) expression, activated astrocytes/microglia, APs and NFTs in AD-affected brain regions. METHODS: Brain sections were stained with Thioflavin-S to study AD pathology and sequentially immunolabeled with antibodies against GMF, glial fibrillary acidic protein (marker for reactive astrocytes), and Ionized calcium binding adaptor molecule 1 (Iba-1, marker for activated microglia) followed by visualization with avidin-biotin peroxidase complex. RESULTS: Our double immunofluorescence labelling with cell-specific markers demonstrated the glial localization of GMF. The immunohistochemical data showed that APs and NFTs are associated with increased expression of GMF in reactive glia of AD brains compared with non-AD controls. CONCLUSIONS: This is the first report that shows GMF, a mediator of central nervous system inflammation, is expressed in the brain regions affected in AD and that GMF is mainly localized in reactive astrocytes surrounding APs/NFTs. The distribution of GMF-immunoreactive cells in and around Thioflavin-S stained APs and NFTs suggests involvement of GMF in inflammatory responses through reactive glia and a role of GMF in AD pathology.

Furosemide-Induced Thrombotic Thrombocytopenic Purpura: A Report of a Rare Case.

Drug-induced immune thrombocytopenia (DITP) refers to drug-dependent, antibody-mediated platelet destruction. Although several drugs have been implicated as the cause of DITP, the most commonly encountered are heparin, sulfonamides, quinine, vancomycin, and beta-lactam antibiotics. However, furosemide has been rarely reported as the cause of thrombocytopenia. We present a unique case of furosemide-induced thrombotic thrombocytopenia in a 64-year-old female referred by her primary care provider for low platelets, rash, and bleeding. She was recently started on oral furosemide for diastolic heart failure two weeks before this presentation. She was admitted to the intensive care unit and was worked up for new-onset thrombocytopenia. Labs revealed anemia, thrombocytopenia, elevated lactate dehydrogenase, and low haptoglobin with normal serum creatinine. Peripheral smear showed schistocytes, low platelets, and ADAMTS13 level was 0.03. The patient was diagnosed with thrombotic thrombocytopenic purpura and treated with steroids, rituximab, and plasmapheresis, which led to rapid recovery of the platelet count to normal. Based on this case report, clinicians should consider furosemide as one of the drugs potentially causing thrombotic thrombocytopenia. Early detection and prompt management can be lifesaving.

Percutaneous Tracheostomy: A Bedside Procedure.

Percutaneous tracheostomy is a bedside surgical procedure that creates an opening in the anterior tracheal wall. Tracheostomy is performed in patients expected to require mechanical ventilation for longer than seven to 10 days. This bedside percutaneous tracheostomy has been used since the late 1990s. Tracheotomy tubes are of various kinds like cuffed vs. uncuffed, fenestrated vs. unfenestrated, single lumen vs. double lumen, and metal vs. plastic. Its indications are categorized into emergency vs. elective. The most common emergency indication is acute airway obstruction, and the elective indication is prolonged intubation. There is no absolute contraindication, but a physician should consider severe hypoxia requiring high oxygen and coagulopathy. Percutaneous tracheostomy is a new technique requiring different skills. Advantages of percutaneous tracheostomy are as follows - it is performed at the bedside, procedural time is less, the cost is less, does not need operating schedule time. Percutaneous tracheostomy is generally performed by otolaryngologists, general surgeons, interventional pulmonologists, thoracic surgeons, or intensivists.

Mitomycin-Induced Thrombotic Thrombocytopenic Purpura Treated Successfully With Plasmapheresis and Steroid: A Case Report.

Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy (TMA) caused by severely reduced ADAMTS13 or the von Willebrand factor-cleaving protease (VWFCP) enzyme resulting in low platelet and red blood cell counts along with severe renal, cardiac, and neurological dysfunction. Plasmapheresis is the treatment of choice. Mitomycin, a widely used chemotherapeutic agent for gastrointestinal (GI) cancers anal and breast cancers, has been reported to occasionally cause severe TTP and hemolytic uremic syndrome (HUS) cases. Here, we present a case of a 57-year-old African American transgender patient who presented with worsening kidney function, thrombocytopenia, and anemia following mitomycin therapy for her anal squamous cell carcinoma. Peripheral smear showed numerous schistocytes, and the patient was diagnosed with TTP because of low ADAMTS13 levels. The patient was started on plasmapheresis and steroid with ultimate improvement in condition. TTP is a rare condition that can be idiopathic or acquired. Further research is required to assess the complexity of the underlying mechanism. Early diagnosis and aggressive management often lead to a favorable outcome.

A Preemptive Living Donor Renal Transplant in an HIV Positive Patient from an HIV Positive Donor.

With recent advances in the treatment of human immunodeficiency virus (HIV), renal transplantation is no longer considered a contraindication in properly selected HIV-positive patients. Several studies have demonstrated comparable patient and graft outcomes between HIV-negative and HIV-positive renal transplant recipients. Most of the information on outcomes of HIV-positive to HIV-positive transplantation is based on data from deceased donors. There are only a handful of case reports about living donor renal transplantation in an HIV-positive patient from an HIV-positive donor. Furthermore, there is no report in the world of preemptive living donor renal transplantation in this setting. Here, we report a case of successful preemptive renal transplantation in an HIV-positive recipient from an HIV-positive living donor performed at our center.

A Case of Severe Epstein-Barr Virus-Associated Hemophagocytic Lymphohistiocytosis Successfully Treated With High Dose Steroids and Ganciclovir.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hematological disorder characterized by immune dysregulation with multiple organ involvement and carries a poor prognosis. The occurrence of HLH can be familial or sporadic, which is triggered by causes like infection or malignancy. This case report is about a 47-year-old male who presented to the hospital with a fever, chills, night sweats, and unintentional weight loss. He was found to have severely elevated ferritin, and computed tomography showed cirrhosis, a normal sized spleen, and retroperitoneal lymphadenopathy. He underwent an extensive battery of tests to identify the etiology. Meanwhile, he had recurrent fevers with worsening transaminitis and septic shock, requiring admission to the ICU. Blood tests for Epstein-Barr virus (EBV) deoxyribonucleic acid (DNA) and immunoglobulin G (IgG) were positive. Due to high suspicion of HLH, he was started on intravenous methylprednisone 1000 mg daily for three days with clinical improvement. A bone marrow biopsy showed hemophagocytosis and he was diagnosed with EBV-associated HLH. He was continued on steroids with oral prednisone and continued to clinically improve. He was later tapered off steroids over the course of five months. HLH is a rapidly progressive and fatal condition that requires prompt treatment, and thus a high index of suspicion is needed to make a timely diagnosis.

An Atypical Presentation of a Severe Case of Anaplasma Phagocytophilum.

We report a case of a 79-year-old male presenting to a South Bronx hospital with complaints of fever, shortness of breath, severe thrombocytopenia, hematuria, elevated liver enzymes, and acute renal failure. The patient rapidly progressed to acute hypoxic respiratory failure requiring mechanical ventilation. Treatment was delayed for six days because the tick-borne disease was not considered in the differential. Empirical treatment of tick-borne illnesses should be considered in the proper clinical setting, and travel history should be relevant in any patient presenting with fever. Delay in appropriate treatment results in the onset of more severe illness.

Ophthalmoparesis and Bilateral Ptosis as a Rare Manifestation of Todd's Phenomenon: Case Report and Review.

Todd's paresis or phenomenon (TP) is a focal weakness in a part of the body after a seizure. Seizure is an abrupt change in behavior caused by the cerebral cortex's electrical hyper-synchronization of neuronal networks. After the seizure, there is usually a transition period from the ictal state to the pre-seizure baseline level of awareness and function, referred to as the postictal period. Postictal symptoms include many systems, including sensory, motor, and psychosis. This phenomenon is named after Robert Bentley Todd, who first described it. Todd's paresis can be confused with other conditions, most commonly a stroke. Postictal ocular manifestation may be accompanied by aphasia or hemiplegia, but isolated gaze palsy is rarely reported. We are reporting a rare and first known isolated ophthalmoparesis and ptosis as postictal findings with no structural abnormalities present in imaging studies and complete resolution over three weeks on its own as an atypical postictal phenomenon. Patients with an underlying structural abnormality of the brain are more susceptible to Todd's phenomenon. Unusual manifestations of Todd's phenomenon are rare but clinically relevant and are decisive in therapeutic decision-making. Our patient presents a rare manifestation of Todd's phenomenon as ptosis and ophthalmoparesis in an elderly male with no underlying structural brain abnormalities that resolved within three weeks. Further research into the causes is needed to distinguish it from a stroke.