Four-Way Wada: SEEG-based mapping with electrical stimulation, high frequency activity, and phase amplitude coupling to complement traditional Wada and functional MRI prior to epilepsy surgery.

Presurgical evaluation of refractory epilepsy involves functional investigations to minimize postoperative deficit. Assessing language and memory is conventionally undertaken using Wada and fMRI, and occasionally supplemented by data from invasive intracranial electroencephalography, such as electrical stimulation, corticortical evoked potentials, mapping of high frequency activity and phase amplitude coupling. We describe the comparative and complementary role of these methods to inform surgical decision-making and functional prognostication. We used Wada paradigm to standardize testing across all modalities. Postoperative neuropsychological testing confirmed deficit predicted based on these methods.

Oncology clinical trial disruption during the COVID-19 pandemic: a COVID-19 and cancer outcomes study.

BACKGROUND: COVID-19 disproportionately impacted patients with cancer as a result of direct infection, and delays in diagnosis and therapy. Oncological clinical trials are resource-intensive endeavors that could be particularly susceptible to disruption by the pandemic, but few studies have evaluated the impact of the pandemic on clinical trial conduct. PATIENTS AND METHODS: This prospective, multicenter study assesses the impact of the pandemic on therapeutic clinical trials at two large academic centers in the Northeastern United States between December 2019 and June 2021. The primary objective was to assess the enrollment on, accrual to, and activation of oncology therapeutic clinical trials during the pandemic using an institution-wide cohort of (i) new patient accruals to oncological trials, (ii) a manually curated cohort of patients with cancer, and (ii) a dataset of new trial activations. RESULTS: The institution-wide cohort included 4756 new patients enrolled to clinical trials from December 2019 to June 2021. A major decrease in the numbers of new patient accruals (-46%) was seen early in the pandemic, followed by a progressive recovery and return to higher-than-normal levels (+2.6%). A similar pattern (from -23.6% to +30.4%) was observed among 467 newly activated trials from June 2019 to June 2021. A more pronounced decline in new accruals was seen among academically sponsored trials (versus industry sponsored trials) (P < 0.05). In the manually curated cohort, which included 2361 patients with cancer, non-white patients tended to be more likely taken off trial in the early pandemic period (adjusted odds ratio: 2.60; 95% confidence interval 1.00-6.63), and substantial pandemic-related deviations were recorded. CONCLUSIONS: Substantial disruptions in clinical trial activities were observed early during the pandemic, with a gradual recovery during ensuing time periods, both from an enrollment and an activation standpoint. The observed decline was more prominent among academically sponsored trials, and racial disparities were seen among people taken off trial.

Manifestaciones orales y disfunción olfativa y gustativa en el síndrome respiratorio agudo severo por corona virus 2 (VIRUS SARS-COV-2): una revisión sistemáticaA / Oral Manifestations and Olfactory and Gustatory Dysfunction in Severe Acute Respiratory Syndrome Corona Virus 2 (SARSCov-2 Virus) Disease: A Systematic Review

La enfermedad del corona virus 2 del síndrome respiratorio agudo severo (virus SARS-CoV-2) apareció por primera vez en diciembre de 2019 en Wuhan, China, y desde entonces se ha extendido rápidamente por todo el mundo. Desde entonces, el brote de esta grave enfermedad viral se ha convertido en una amenaza global para la humanidad. El diagnóstico precoz y el aislamiento son las medidas más importantes necesarias para prevenir su propagación. La evidencia anecdótica reciente ha sugerido manifestaciones orales con o sin deterioro olfativo y gustativo en asociación con la enfermedad por coronavirus (COVID-19). La enzima convertidora de angiotensina-2 (ECA-2) se expresa en la mucosa oral en grandes cantidades y, por tanto, puede contribuir a las primeras manifestaciones de esta enfermedad viral mortal. Las manifestaciones bucales de la enfermedad por coronavirus pueden presentarse en forma de lesiones ulcerativas irregulares en relación con diferentes partes de la cavidad oral y, en particular, en relación con la mucosa adherida en la región del paladar duro, así como inflamación y posterior atrofia de las diversas papilas de la lengua. La disfunción olfativa y gustativa asociada también puede conducir a una pérdida parcial y / o incluso completa de la capacidad para oler y saborear en las primeras etapas del inicio de la enfermedad. La evidencia también ha sugerido la presencia de ácido nucleico del SARS-CoV-2 en la saliva humana, lo que la convierte en portadora de la enfermedad viral infecciosa y ayuda en su diagnóstico. Hemos buscado sistemáticamente la base de datos médica para el mismo y hemos revisado toda la literatura disponible hasta el 29 de junio de 2020

Severe acute respiratory syndrome corona virus 2 (SARS-CoV-2 virus) disease had first appeared in December 2019 in Wuhan, China and has been spreading quickly throughout the world since then. Since then, the outbreak of this severe viral disease has become a global threat to humanity. An early diagnosis and isolation are the most significant measures required to prevent its spread. Recent anecdotal evidence has suggested oral manifestations with or, without olfactory and gustatory impairment in association with corona virus disease (COVID-19). Angiotensin converting enzyme-2 (ACE-2) is expressed in oral mucosa in large amounts and can, thus, contribute in the early manifestations of this deadly viral disease. The oral manifestations of corona virus disease can occur in the form of irregular ulcerative lesions in relation to different parts of the oral cavity and particularly, in relation to the attached mucosa in the hard palate region as well as inflammation and subsequent, atrophy of the various tongue papilla. The associated olfactory and gustatory dysfunction can, also, lead to partial and/or, even a complete loss of the ability to smell and taste in the early stages of the disease onset. Evidence has, also, suggested the presence of SARS-CoV-2 nucleic acid in human saliva making it the carrier of the infectious viral disease as well as aiding in its diagnosis. We have systemically searched medical database for the same and have reviewed all the literature available up to 29th of June 2020.

A seven-month-old with chronic intermittent biphasic stridor.

Paediatric stridor can indicate serious pathology and requires prompt evaluation and management. Causes range from laryngomalacia to aerodigestive tract foreign bodies. We report on a chronic presentation of paediatric stridor, discuss the workup, management and lessons learned. A seven-month-old boy presented with chronic intermittent biphasic stridor for the previous five months. Diagnostic microlaryngoscopy and bronchoscopy revealed significant localised tracheomalacia. Urgent chest computed tomography was performed to investigate further. Radiological findings revealed an oesophageal foreign body prompting immediate rigid oesophagoscopy and removal of an embedded pistachio shell. The patient had an uneventful recovery. Foreign bodies in the airway and oesophagus are quite common in children, causing symptoms from the aerodigestive tract. It is uncommon for oesophageal foreign bodies to present with stridor in the absence of digestive tract symptoms. The otolaryngologist should consider this as a diagnosis, particularly in young children with an atypical presentation and symptoms.

Non-canonical Wnt signalling regulates scarring in biliary disease via the planar cell polarity receptors.

The number of patients diagnosed with chronic bile duct disease is increasing and in most cases these diseases result in chronic ductular scarring, necessitating liver transplantation. The formation of ductular scaring affects liver function; however, scar-generating portal fibroblasts also provide important instructive signals to promote the proliferation and differentiation of biliary epithelial cells. Therefore, understanding whether we can reduce scar formation while maintaining a pro-regenerative microenvironment will be essential in developing treatments for biliary disease. Here, we describe how regenerating biliary epithelial cells express Wnt-Planar Cell Polarity signalling components following bile duct injury and promote the formation of ductular scars by upregulating pro-fibrogenic cytokines and positively regulating collagen-deposition. Inhibiting the production of Wnt-ligands reduces the amount of scar formed around the bile duct, without reducing the development of the pro-regenerative microenvironment required for ductular regeneration, demonstrating that scarring and regeneration can be uncoupled in adult biliary disease and regeneration.

Pleural tumours and tumour-like lesions.

There are various neoplasms and tumour-like conditions of the pleura. Mesothelioma is perhaps the most widely recognised; however, there are many others that are more common and should be considered. Understanding the similarities and differences can be helpful in managing the patient with a newly found pleural lesion. We will discuss clinical symptoms at presentation and describe the imaging findings associated with these tumours, starting with conventional radiology, and correlating with computed tomography and combined positron-emission tomography (PET)/computed tomography (CT). Finally, imaging characteristics that help differentiation between the benign and malignant varieties will be reviewed.

Extramedullary haematopoiesis: radiological imaging features.

Extramedullary haematopoiesis (EMH) is defined as the production of blood cells outside of the bone marrow, which occurs when there is inadequate production of blood cells. The most common causes of EMH are myelofibrosis, diffuse osseous metastatic disease replacing the bone marrow, leukaemia, sickle cell disease, and thalassemia. The purpose of this article is to review the common and uncommon imaging appearances of EMH by anatomical compartment. In the thorax, EMH most commonly presents as paravertebral fat-containing masses, and typically does not present a diagnostic dilemma; however, EMH in the abdomen most commonly manifests as hepatosplenomegaly with or without focal soft-tissue masses in the liver, spleen, perirenal space, and in the peritoneum. Hepatosplenomegaly, a non-specific feature, most often occurs without an associated focal mass, which makes suggestion of EMH difficult. EMH manifesting as visceral soft-tissue masses often requires biopsy as the differential diagnosis can include lymphoma, metastatic disease, and sarcoma. Many of these soft-tissue masses do not contain adipose elements, making the diagnosis of EMH difficult. Clinical history is crucial, as EMH would likely not otherwise be in the differential in patients with non-specific abdominal masses. Careful biopsy planning is necessary when EMH is a diagnostic consideration, given the propensity for haemorrhage. Understanding the typical imaging appearances of EMH based on its site of manifestation can help the radiologist when encountered with a finding that is diagnostic for EMH, and can help the radiologist suggest the need and plan appropriately for image-guided biopsy.

Human epidermal growth factor receptor 2 expression in gastric carcinoma and its association with histopathological parameters in Indian population.

INTRODUCTION: Gastric carcinoma is a leading cause of death worldwide with a five year survival of 10-15% even after curative resection. Trastuzumab has emerged as a potential targeted therapy in treatment of Her 2 positive gastric cancer. Her2 positivity ranges from 7-34% in studies across the world. There is a paucity of Indian studies hence a need for determination of Her2 expression in Indian population for better patient management. This study was carried out to determine the frequency of Her 2 expression in gastric carcinoma by immunohistochemistry (IHC) technique and to evaluate its association with histopathological parameters. MATERIAL AND METHODS: A total of 110 cases of gastric adenocarcinoma diagnosed on histopathological examination from July 2013 to June 2015 were included. Of these, 40 cases were resection specimens and 70 were biopsies. Histological typing of gastric carcinoma was done on the basis of Lauren classification. IHC for Her2 was done in all 110 cases. Her 2 expression was correlated with various histopathological parameters. RESULTS: Positive Her 2 expression (IHC 3+) was seen in 24.5% cases of gastric carcinoma. Patients in older age group(> 60 years) showed higher Her 2 positivity rate as compared to middle age (40-60 years) and younger population (<40 years). Higher percentage of Her 2 positivity was noted in male patients as compared to female patients. Her 2 positivity was seen more commonly in intestinal type of tumor as compared to diffuse and mixed types. Her 2 positivity was seen more in well differentiated carcinoma and higher stage tumors (pT3 and pT4). However, out of all, a statistically significant association of Her2 expression was found only with (intestinal) type of tumors (p= 0.005) and no significant association was seen with age, gender, site of tumor, tumor stage, lymph node status, lymphovascular, perineural and perinodal invasion or survival. CONCLUSION: Inspired by promising results of Trastuzumab therapy in Her 2 positive gastric carcinoma worldwide, it is recommended to routinely test all cases of gastric carcinoma for Her 2 expression and to use the targeted therapy with curative intentions in Indian population.

Cost-minimization analysis for Portugal of five doublet chemotherapy regimens from two phase III trials in the treatment of advanced non-small cell lung cancer.

OBJECTIVES: Economic evaluations of chemotherapy regimens for stage IIIB or IV non-small cell lung cancer (NSCLC) have been conducted for many European countries, but not for Portugal. This study evaluates the total health care costs of five commonly used doublet regimens with similar efficacy results. METHODS: Using the methodology reported by Schiller [Schiller JH, Tilden D, Aristides M, Lees M, Kielhorn A, Maniadakis N, et al. Restropective cost analysis of gemcitabine in combination with cisplatin in non-small cell lung cancer compared to other combination therapies in Europe. Lung Cancer 2004;43:101-12], we conducted a cost-minimization analysis to compare vinorelbine-cisplatin (Vin/Cis), gemcitabine-cisplatin (Gem/Cis), paclitaxel-carboplatin (Pac/Carb), docetaxel-cisplatin (Doc/Cis), and paclitaxel-cisplatin (Pac/Cis). The perspective was that of the Portuguese National Health Service and included only direct medical costs (reimbursed costs plus co-payments): chemotherapy acquisition, chemotherapy administration, hospitalizations due to adverse events, and other medical resources. Unit costs were drawn from official sources (Diagnosis Related Groups and retail/hospital costs) (2003 value [Diagnosis Related Groups (DRG) published at Diário da República; 2003]). Resource use was estimated from two multicenter randomized phase III trials [Comella P, Frasci G, Panza N, Manzione L, De Cataldis G, Cioffi R, et al. Randomized trial comparing cisplatin, gemcitabine, and vinorelbine with either cisplatin and gemcitabine or cisplatin and vinorelbine in advanced non-small-cell lung cancer: interim analysis of a phase III trial of the Southern Italy Cooperative Oncology Group. J Clin Oncol 2000;18:1451-7; Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, et al. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med 2002;346:92-8]. A time horizon of a full course of therapy was adopted. One-way sensitivity analyses were performed. RESULTS: The least and the most costly chemotherapy regimens were Gem/Cis and Pac/Carb, respectively. Total mean cost per patient was estimated at euro7083 for Gem/Cis and euro10,008 for Pac/Carb, a mean cost savings of euro2925 per patient for Gem/Cis. The differences were mainly due to the higher chemotherapy acquisition costs of Pac/Carb than for Gem/Cis. Gem/Cis was less costly in all sensitivity analyses except when 100% inpatient chemotherapy administration was assumed. CONCLUSION: Gem/Cis should be considered as a cost-saving alternative to the other four regimens in treating NSCLC patients in Portugal.

Leucocytoclastic vasculitis as a presentation of adenocarcinoma rectum.

Vasculitis has been linked to several processes, like infections, drugs and allergic, rheumatologic and neoplastic diseases. Neoplasm-associated vasculitis described in the medical literature has mostly been reported in association with haemotological neoplasms. Adenocarcinoma of rectum presenting as leucocytoclastic vasculitis is rare. We present a case of a 43-year-old male with paraneoplastic leucocytoclastic vasculitis preceding the manifestation of adenocarcinoma rectum. The vasculitis subsided on resection of the rectal malignancy and the patient did not require steroid therapy thereafter.

Determining patient preferences for improved chemotoxicity during treatment for advanced bladder cancer.

Determining patient preferences for improved chemotoxicity during treatment for advanced bladder cancer Conventional treatment for advanced bladder cancer is methotrexate, vinblastine, doxorubicin plus cisplatin (MVAC), with a median survival of 1 year but significant toxicity. The newer combination of gemcitabine plus cisplatin (GC) has demonstrated comparable survival and an improved toxicity profile (Von der Maase et al. 2000). At present, the importance to patients of the toxicity of chemotherapy has not been widely studied. An earlier study in bladder cancer indicated that toxicity was an important determinant of treatment preference (Davey et al. 2000). A study of preferences for advanced bladder cancer therapy in the UK was proposed.

Isolated submandibular gland metastasis from an occult papillary thyroid cancer.

A case of an isolated submandibular gland metastasis from a clinically occult papillary thyroid carcinoma is described in a 46-year old lady. Initial surgery was done based on the fine needle aspiration cytology (FNAC) report of adenocarcinoma of the submandibular gland. Histopathologic examination of the specimen suggested a metastatic papillary carcinoma. Occult papillary carcinoma in the thyroid was found by multiple blind FNACs. Subsequently to near-total thyroidectomy, no other site of metastasis was found on radio-iodine scanning.

The effect of recent trauma on serum complement activation and serum C3 levels correlated with the injury severity score.

PURPOSE: The objective of this prospective pilot study was to estimate serum C3 levels and complement activation within 12 hours of injury and to correlate them with abbreviated injury score (AIS) so as to predict the outcome of injury in terms of mortality or sepsis. METHODS: The test group (n=30) of patients with < 12 hours of injury were assessed by the AIS-80 and compared with a control group (n=10). Serum C3 levels were estimated by the single radial immunodiffusion technique and complement activation by both two-dimensional and counter immuno-electrophoresis. Statistical analysis was performed using the correlation regression analysis and the minimum discrimination information statistics (MDIS) analysis. RESULTS: Serum C3 levels were not reduced in patients with injury severity score (ISS) < 12 (n=7). There was a statistically significant difference of serum C3 levels in patients with ISS between 12 and 29 (n=15) and in patients with ISS more than 29 (n=9). Complement activation also correlated well with ISS (p < 0.05). Complement activation and serum C3 levels were found to influence subsequent development of septic complications in the post injury period, being significantly lower in patients who developed septic complications. Complement alterations in trauma patients were a direct result of the trauma since they were not seen in patients undergoing surgery. CONCLUSIONS: ISS is a good prognosticator of outcome of trauma and serum C3 levels and complement activation are good predictors for mortality and development of septic complications in recently injured patients. These may prove to be effective parameters in the management of the patients with injury.

Sixth nerve schwannoma: a case report with literature review.

A 40-year-old woman presented with diplopia and left VI nerve palsy. After investigations, diagnosis of a meningioma in the parasellar-prepontine region was considered. Following angiography and embolization, near-total excision of the tumour attached to abducens nerve was performed. Histological examination was consistent with the diagnosis of schwannoma. This is the thirteenth case report of a schwannoma of cranial nerve VI and the first such case where embolization of feeding tumour vessels was performed.

Hodgkin's disease and scleroderma.

We report here the uncommon association between scleroderma and Hodgkin's disease in a 42 years male.

Malignant peripheral nerve sheath tumor of the cauda equina.

Only one case of malignant peripheral nerve sheath tumor (MPNST) affecting the cauda equina region has been reported earlier. A 32-year-old male with congenital multiple subcutaneous swellings presented with low back pain, progressive paraparesis and bladder-bowel dysfunction. Magnetic resonance imaging (MRI) demonstrated a heterogeneously enhancing intradural lesion at L2-L4. At operation, on opening the dura, multiple nodular, firm matted masses attached to the lumbosacral nerve roots were encountered. Peripheral lesions were partially excised. Histopathological exam revealed varied cellularity with necrosis and pleomorphic nuclei suggestive of MPNST. MRI features, pathophysiological characteristics and the literature are reviewed.

Fine needle aspiration cytology of a dedifferentiated liposarcoma: report of a case with histologic and immunohistochemical follow-up.

BACKGROUND: Dedifferentiation is a histologic progression of a neoplasm from low grade to high grade histology. It occurs in tumors of the retroperitoneum and in those undergoing treatment. This usually occurs in the setting of radiation or chemotherapy or as a spontaneous process over a long period. The features of dedifferentiation can be toward any mesenchymal element of the underlying neoplastic process. CASE: We report the cytologic features of a dedifferentiated liposarcoma arising in a 76-year-old man who had a history of well-differentiated liposarcoma. Papanicolaou- and Diff-Quik-stained smears from a radiologically guided fine needle aspiration biopsy showed a hypercellular sample. The smears showed a mixed population of cells. There were multinucleated, pleomorphic giant cells with abundant cytoplasm, smaller clusters of cells with a high nuclear/cytoplasmic ratio and cells with spindled and elongated nuclear features. The follow-up surgical resection specimen showed a dedifferentiated liposarcoma with strong and diffuse immunoreactivity to vimentin, desmin and CD68 in the large, pleomorphic cells; focal and weak immunoreactivity to smooth muscle actin and S-100 in these cells; and strong and focal immunoreactivity to desmin, smooth muscle actin and muscle-specific actin in the spindle cells. This supports the dedifferentiated components of this tumor to be of fibrohistiocytic and leiomyosarcomatous differentiation. CONCLUSION: Dedifferentiation of a well-differentiated liposarcoma should be entertained in the setting of a mass lesion in the retroperitoneum in patients with prior histories of well-differentiated liposarcoma. The radiologic features of a particular neoplastic process can be very helpful in determining the nature of this process.

Newly synthesized human delta opioid receptors retained in the endoplasmic reticulum are retrotranslocated to the cytosol, deglycosylated, ubiquitinated, and degraded by the proteasome.

We have previously shown that only a fraction of the newly synthesized human delta opioid receptors is able to leave the endoplasmic reticulum (ER) and reach the cell surface (Petäjä-Repo, U. E, Hogue, M., Laperrière, A., Walker, P., and Bouvier, M. (2000) J. Biol. Chem. 275, 13727-13736). In the present study, we investigated the fate of those receptors that are retained intracellularly. Pulse-chase experiments revealed that the disappearance of the receptor precursor form (M(r) 45,000) and of two smaller species (M(r) 42,000 and 39,000) is inhibited by the proteasome blocker, lactacystin. The treatment also promoted accumulation of the mature receptor form (M(r) 55,000), indicating that the ER quality control actively routes a significant proportion of rescuable receptors for proteasome degradation. In addition, degradation intermediates that included full-length deglycosylated (M(r) 39,000) and ubiquitinated forms of the receptor were found to accumulate in the cytosol upon inhibition of proteasome function. Finally, coimmunoprecipitation experiments with the beta-subunit of the Sec61 translocon complex revealed that the receptor precursor and its deglycosylated degradation intermediates interact with the translocon. Taken together, these results support a model in which misfolded or incompletely folded receptors are transported to the cytoplasmic side of the ER membrane via the Sec61 translocon, deglycosylated and conjugated with ubiquitin prior to degradation by the cytoplasmic 26 S proteasomes.