Medicine

Electrophysiological grading scale for polyneuropathy severity

Objective To establish a simple electrophysiological scale for patients with distal symmetric axonal polyneuropathy, in order to promote standardized and informative electrodiagnostic reporting, and understand the complex relationship between electrophysiological and clinical polyneuropathy severit...
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Objective To establish a simple electrophysiological scale for patients with distal symmetric axonal polyneuropathy, in order to promote standardized and informative electrodiagnostic reporting, and understand the complex relationship between electrophysiological and clinical polyneuropathy severity. Methods We included 76 patients with distal symmetric axonal polyneuropathy, from a cohort of 151 patients with polyneuropathy prospectively recruited from November 2016 to May 2017. Patients underwent nerve conduction studies (NCS), were evaluated by the Toronto Clinical Neuropathy Score (TCNS), and additional tests. The number of abnormal NCS parameters was determined, within the range of 0–4, considering low amplitude or conduction velocity in the sural and peroneal nerve. Results Higher number of NCS abnormalities was associated with higher TCNS, indicating more severe polyneuropathy. Polyneuropathy severity per the TCNS was most frequently (63%-70%) mild in patients with a low (0–1) number of NCS abnormalities, and most frequently (57%-67%) severe in patients with a high number (3–4) of NCS abnormalities, while patients with an intermediate (2) number of NCS abnormalities showed mainly mild and moderate severity with equal distribution (40%). Conclusions A simple NCS classification system can objectively grade polyneuropathy severity, although significant overlap exists especially at the intermediate range, underscoring the importance of clinical based scoring.
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Reducing low-value imaging - stakeholders’ assessment of an intervention to improve imaging services

Abstract Background An intervention to reduce low-value magnetic resonance imaging (MRI) was designed and implemented in private imaging centres in Norway in October 2022. The intervention used return letters for poor referrals of MRI of the lower back, brain and kn...
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Abstract Background An intervention to reduce low-value magnetic resonance imaging (MRI) was designed and implemented in private imaging centres in Norway in October 2022. The intervention used return letters for poor referrals of MRI of the lower back, brain and knee at private imaging centres in Norway. The study aimed to investigate key stakeholders’ experiences and assessment of the intervention and the specific research questions were: • How many return letters were sent during the study period? • What were the medical directors’ and managers’ experiences with and reflection on success factors for the intervention implementation and using return letters? Methods The number of return letters sent was collected directly from Norway’s two main private imaging providers. Two semi-structured individual interviews were conducted with the medical directors of the imaging providers, as well as two focus group interviews with nine managers from the various private imaging centres operated by the two imaging providers. Results In total, 1,182 return letters were sent for patients undergoing one of the three types of MRI examinations, and the number of return letters was highest at the beginning of the intervention. The interview analysis resulted in five categories: general experience, anchoring, organisation, return letter procedure and outcome. Sufficient information, anchoring and support were identified as crucial success factors. Conclusions This study provides insights into the practical and crucial details of implementing interventions to reduce low-value imaging. The intervention was generally well received, and the high initial number of return letters decreased rapidly over the course of the study. Several key success factors were identified.
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Rural household vulnerability and COVID-19: Evidence from India

The coronavirus disease 2019 (COVID-19) pandemic has affected vulnerable households’ livelihoods in developing countries. Using high-frequency phone survey data from the World Bank, we assess rural Indian households’ vulnerability and poverty status during the pandemic. Results reveal that over ...
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The coronavirus disease 2019 (COVID-19) pandemic has affected vulnerable households’ livelihoods in developing countries. Using high-frequency phone survey data from the World Bank, we assess rural Indian households’ vulnerability and poverty status during the pandemic. Results reveal that over three-fifths of Indian rural households are vulnerable to poverty in the context of COVID-19, despite India’s evident progress in mitigating poverty in the pre-pandemic era. Poverty plays a major role in accounting for variations in household vulnerability; however, the impact of risks on household welfare is not negligible. On average, households with more members, older household heads, and more outmigrants are more vulnerable to poverty during the pandemic. The impacts of the gender of the household head, access to masks, consumption loans, and COVID-related information are nevertheless insignificant. Results stress the urgent necessity of deploying concerted interventions to strengthen household vulnerability in rural India.
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Growth and Progression of TRAMP Prostate Tumors in Relationship to Diet and Obesity

To clarify effects of diet and body weight on prostate cancer development, three studies were undertaken using the TRAMP mouse model of this disease. In the first experiment, obesity was induced by injection of gold thioglucose (GTG). Age of prostate tumor detection (~33 wk) and death (~43 wk) w...
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To clarify effects of diet and body weight on prostate cancer development, three studies were undertaken using the TRAMP mouse model of this disease. In the first experiment, obesity was induced by injection of gold thioglucose (GTG). Age of prostate tumor detection (~33 wk) and death (~43 wk) was not significantly different among the groups. In the second study, TRAMP-C2 cells were injected into syngeneic C57BL6 mice and tumor progression was evaluated in mice fed either high-fat or low-fat diets. The high fat fed mice had larger tumors than did the low-fat fed mice. In the third study, tumor development was followed in TRAMP mice fed a high fat diet from 6 weeks of age. There were no significant effects of body weight status or diet on tumor development among the groups. When the tumors were examined for the neuroendocrine marker synaptophysin, there was no correlation with either body weight or diet. However, there was a significant correlation of the expression of synaptophysin with earlier age to tumor detection and death. In summary, TRAMP-C2 cells grew faster when the mice were fed a high-fat diet. Further synaptophysin may be a marker of poor prognosis independent of weight and diet.
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A Gene Therapy for Hereditary Nonpolyposis Colorectal Cancer using CRISPR-Cas9 Nickase

Hereditary non-polyposis colorectal cancer (HNPCC) is an inherited disorder characterized by an increased risk of developing colorectal cancer before age 50. HNPCC is predominantly caused by genetic mutations in MLH1 and MSH2, which are involved in DNA mismatch repair. Current standard practice is t...
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Hereditary non-polyposis colorectal cancer (HNPCC) is an inherited disorder characterized by an increased risk of developing colorectal cancer before age 50. HNPCC is predominantly caused by genetic mutations in MLH1 and MSH2, which are involved in DNA mismatch repair. Current standard practice is to perform prophylactic colectomy, resulting in debilitating aftereffects for life. Though the genetic cause of HNPCC is well-known, there are currently no available treatments that target these mutations. Herein we describe a novel treatment protocol using a CRISPR-Cas9n-based genetic therapy to restore DNA mismatch repair. First, gRNA and template DNA targeting the most prevalent mutation clusters in MLH1 and MSH2 as well as CRISPR-Cas9n elements will be packaged into an integrase-deficient lentiviral vector. Then, the viral vector will be used to transduce human colonic tumor-derived organoids as well as administered systemically in mouse models of HNPCC. Mice will be monitored clinically and for signs of disease progression. At termination, colonic tissue will be harvested and analyzed for restoration of the wild-type MLH1 and MSH2 sequence and biochemical markers of HNPCC. This protocol offers an alternative strategy using CRISPR-Cas9n-based gene therapy to prevent tumor formation in patients, avoid morbid surgery, and significantly improve quality of life.
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Review of Hereditary non-polyposis colorectal cancer

The purpose of this paper is to provide a review of hereditary non-polyposis colorectal cancer. This paper covers the causes, epidemiology, pathophysiology, histology, diagnosis, and treatment for the disease.

Clear cell and papillary renal cell carcinomas in hereditary papillary renal cell carcinoma (HPRCC) syndrome: a case report

Background Hereditary papillary renal cell carcinoma (HPRCC) is a rare autosomal dominant disease characterized by the development of multiple and bilateral papillary type I renal cell carcinomas (RCC) and papillary adenomas caused by activating mutations in the MET proto-oncogene. Classically, dis...
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Background Hereditary papillary renal cell carcinoma (HPRCC) is a rare autosomal dominant disease characterized by the development of multiple and bilateral papillary type I renal cell carcinomas (RCC) and papillary adenomas caused by activating mutations in the MET proto-oncogene. Classically, distinctive histological features of RCC are described according to the familial renal cell carcinoma syndrome. To date, no clear cell RCC has been reported in HPRCC syndrome. Case presentation We describe the case of a 51-year-old man with a germline MET mutation detected on peripheral blood testing, and no germline VHL mutation, who developed numerous papillary tumors but also unexpectedly clear cell renal cell carcinomas. During the follow-up, an adrenal metastasis was observed 7 years after the initial diagnosis corresponding to a clear cell RCC metastasis. By immunohistochemistry, clear cell tumors showed focal cytokeratin 7, moderate racemase, and diffuse and membranous CAIX expression, while papillary tumors expressed strong diffuse cytokeratin 7 and racemase without CAIX positivity. Using FISH, VHL deletion was observed in one of the clear cell tumors, and the metastatic clear cell tumor presented a trisomy of chromosomes 7 and 17. These last genomic alterations are usually detected in papillary RCC, highlighting the potential link between both histological subtypes of tumors and the HPRCC syndrome. Conclusions The pathologist must be aware that the presence of a non-papillary RCC associated with numerous papillary tumors should not exclude the diagnostic suspicion of HPRCC and thus to perform a thorough genomic study.
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Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC) Syndrome

In hereditary leiomyomatosis and renal cell carcinoma syndrome, fumarate hydratase–deficient renal cell carcinomas typically present as aggressive, unilateral, often cystic masses with heterogeneous enhancement. These tumors can metastasize early, making appropriate imaging and staging critical fo...
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In hereditary leiomyomatosis and renal cell carcinoma syndrome, fumarate hydratase–deficient renal cell carcinomas typically present as aggressive, unilateral, often cystic masses with heterogeneous enhancement. These tumors can metastasize early, making appropriate imaging and staging critical for diagnosis and management. Teaching point: When a renal lesion suspected of RCC is identified in a patient with cutaneous and uterine leiomyomas, HLRCC should be evaluated, which is important for future genetic counseling.
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A Non-Hereditary Case of Hereditary Leiomyomatosis and Renal Cell Carcinoma Syndrome

Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome is believed to result from an autosomal dominant mutation in the fumarate hydratase (FH) gene on chromosome 1. It is characterized by leiomyomas, mainly uterine or cutaneous, and renal cell carcinoma (RCC). The most common type of R...
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Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome is believed to result from an autosomal dominant mutation in the fumarate hydratase (FH) gene on chromosome 1. It is characterized by leiomyomas, mainly uterine or cutaneous, and renal cell carcinoma (RCC). The most common type of RCC associated with HLRCC is type II papillary RCC although other types are seen. Of note, chromophobe RCC has not been described in previously documented cases of HLRCC. HLRCC is typically associated with germline mutations with occasional somatic mutations reported, however, to the best of our knowledge, none have yielded the full phenotype until now. Herein, we report a case of a 45-year-old woman who underwent a hysterectomy following a year of heavy vaginal bleeding, yielding a diagnosis of uterine leiomyomas. Eight months later, the patient presented with hematuria and was subsequently found to have a left renal mass. Following a left radical nephrectomy, histologic exam revealed a chromophobe RCC with FH deficiency.
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A Case of Metastatic Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome-Associated Renal Cell Carcinoma Treated with a Sequence of Axitinib and Nivolumab Following Cytoreductive Nephrectomy

Hereditary leiomyomatosis and renal cell cancer syndrome (HLRCC) associated renal cell carcinoma (RCC) is an aggressive form of type 2 papillary RCC caused by deficiency of the fumarate hydratase gene. For patients with metastatic disease, no standard treatment has been established with dismal progn...
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Hereditary leiomyomatosis and renal cell cancer syndrome (HLRCC) associated renal cell carcinoma (RCC) is an aggressive form of type 2 papillary RCC caused by deficiency of the fumarate hydratase gene. For patients with metastatic disease, no standard treatment has been established with dismal prognosis. We report a case of metastatic HLRCC-associated RCC in a 65-year-old Japanese male whose clinical features mimicked advanced renal pelvic cancer. A durable response was achieved with a sequence of axitinib and nivolumab after cytoreductive and diagnostic nephrectomy. Their potential therapeutic roles in the management of metastatic HLRCC-associated RCC have been discussed based on its molecular and biological backgrounds.
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