Incidence of Colorectal Cancer After Intestinal Infection Due to Clostridioides difficile.

Background: Clostridioides difficile (C. difficile or C. diff) is a toxin-producing bacteria that is notorious for causing life-threatening diarrhea. Recent literature has investigated various effects of Clostridioides difficile infection (CDI) in cancer patients, but research into the impact of CDI on the development of cancer and its effects on the microbiome is limited. CDI predominately affects the colon, which urges consideration into the sequalae of infection. This study investigated the correlation between CDI and the incidence of colorectal carcinoma (CRC). Methods: A retrospective study (2010 - 2020) was conducted using a Health Insurance Portability and Accountability Act (HIPAA) compliant national database. The International Classification of Disease ninth and 10th Codes (ICD-9, ICD-10), Current Procedural Terminology (CPT), and National Drug Codes were used to identify CRC diagnosis, CDI, and matching or control parameters. Patients were matched for age, sex, Charlson Comorbidity Index (CCI), region of residence, and CDI treatment. An additional, but separate, query was executed to include obese patients with and without CDI, who were similarly matched and assessed for CRC. Statistical analyses were implemented to assess significance and estimate odds ratios (ORs). Results: CDI was associated with a decreased incidence of CRC (OR = 0.59, 95% confidence interval (CI): 0.55 - 0.63), and the difference was statistically significant (P < 2.2 × 10-16). CDI treatment, including appropriate antibiotics and fecal microbiota transplant (FMT), was controlled for in both infected and noninfected populations. Patients with a prior CDI who received relevant treatment were compared to patients with no history of CDI and received analogous treatment. Both populations subsequently developed CRC. Results remained statistically significant (P < 2.2 × 10-16) with a relative risk (RR) of 0.57 (95% CI: 0.54 - 0.60). Obesity was explored as a controlled variable in relation to CRC development in patients with and without prior CDI. Obese patients without a history of CDI were found to have a decreased risk of developing CRC. Results were statistically significant (P < 4.3 × 10-13) with an OR of 0.70 (95% CI: 0.63 - 0.77). Conclusions: This study shows a statistically significant correlation between CDI and decreased incidence of CRC. Additionally, there is a statistically significant correlation between obese patients with CDI and an increased incidence of CRC. Further research is needed to explore the mechanism of this striking relationship and the implications of CDIs on the microbiome.

Enteric Dysbiosis in Children With Autism Spectrum Disorder and Associated Response to Stress.

Background Microbiome studies in humans, though limited, have facilitated the evaluation of the potential connection between the microbiome and brain function. Children with autism spectrum disorder (ASD) have several behavioral challenges and avoidant/restrictive food intake disorder, which may contribute to gut microbiome dysbiosis. Aim The aim of this study is to examine the extent to which the gut microbiome of children with ASD differs in comparison to children with neurotypical development (CWND) and to assess whether a probiotic intervention has the potential to influence the gut microbiome in mediating positive behavior change and stress regulation. Methods This pilot study collected data from three children with ASD and four CWND before and after a four-week probiotic intervention. Data collection included microbiome diversity screening from stool samples as well as the following biophysiological measures: salivary alpha-amylase (sAA) levels, response to simulated stressor and calming stimulus (behavior), including pulse rate, galvanic skin response, and pupil diameter (PD). In addition, telomere length was assessed. All measures, except for telomere length, were repeated after the four-week intervention on the ASD and CWND groups for pre-/post-comparison. Data analysis consisted of multivariate analyses, including ANOVA. Results While greater heterogeneity in the ASD group was evident in all measures, the gut microbiome of participants who received probiotic intervention differed from pretreatment results within and across the groups investigated. Further, the biophysiological parameter sAA displayed a significant increase between baseline and exposure to stress in both groups, whereas PD increased in both groups from baseline, F(11, 26615) = 123.43, p = 0.00. Conclusion Though gut microbiome diversity is diminished in children with ASD compared to CWND, the gap is narrowed following a brief probiotic intervention. The results suggest that probiotic interventions have the potential to rescue microbiome diversity and abundance, potentially supporting stress regulation in pediatric populations.

The Role of Crohn Disease on Breast Cancer Incidence: A Clinical Analysis.

Background: Crohn disease is a chronic inflammatory disease that can affect the entire gastrointestinal tract. The pathophysiology of this disease characteristically involves transmural inflammation, which predisposes patients to various gastrointestinal cancers such as colon cancer. Although the increased risk of gastrointestinal cancers in Crohn disease has been well established, the risk of extra-gastrointestinal cancers remains unknown. We sought to study the risk of breast cancer in patients with Crohn disease. Methods: The data for this retrospective study were compiled using the International Classification of Disease Ninth Revision (ICD-9) and ICD 10th Revision (ICD-10) codes from the national Health Insurance Portability and Accountability Act (HIPAA)-compliant PearlDiver database from 2010 to 2019. Patients were matched for age, sex, and Charlson Comorbidity Index (CCI). Statistical analyses were implemented to assess Chi-squared, logistic regression, and odds ratio. Results: The database query resulted in 70,027 patients in both the control and Crohn disease groups. The incidence of breast cancer was 4,087 in the control group compared to 654 in the Crohn disease group. The P value was < 2.2 × 10-16 and the odds ratio was 0.15 (95% confidence interval (CI)). Patients without Crohn disease had an increased prevalence of breast cancer throughout all age ranges compared to patients with Crohn disease. Additionally, patients without Crohn disease had higher rates of breast cancer throughout the four major regions of the United States. In terms of healthcare costs, patients with breast cancer and a history of Crohn disease paid $23.87 more per hospital visit compared to patients with breast cancer and no history of Crohn disease. Conclusions: The results of this study indicate a statistically significant correlation between Crohn disease and a reduced incidence of breast cancer. This finding is true across all age groups and across the United States. Further study is required to investigate a possible mechanism between the pathophysiology of Crohn disease ultimately leading to reduced tumorigenesis in the breast.

Pneumocephalus With Stroke-Like Symptoms: A Rare Complication of Mastoiditis.

Pneumocephalus is defined as the presence of gas or air in the intracranial space and typically arises as a result of neurotrauma. Clinically, pneumocephalus most often presents asymptomatically but may cause headache, nausea, vomiting, and confusion. Pneumocephalus arising from mastoiditis is an unforeseen complication with only a handful of cases reported. We report a case of an elderly male who presented with stroke-like symptoms in the setting of erosive mastoiditis with pneumocephalus.

Role Modeling in Medical Education: A Twenty-First Century Learner's Perspective.

Traditional role modeling is a complex process of observation and emulation delivered by experienced senior physicians with an unknown outcome. Role modeling through organized modalities has been utilized as an educational tool in medical school for years. However, effects of parenting, near peers, gender, race, and social media on role modeling in medical education have not been well characterized yet play a significant role in the development of modern clinicians. The aim of this paper is to encourage students as future medical and clinical educators through an in-depth analysis of role modeling, with the goal of improving their "role modeling consciousness."

Defining Advising, Coaching, and Mentoring for Student Development in Medical Education.

Medical school curricula integrate classroom academic teaching, hands-on clinical training, longitudinal professional development, and identity formation to prepare students to enter the healthcare workforce as residents. Mentorship, coaching, and advising are well-recognized approaches used by educators to help young learners accomplish their personal and professional goals and objectives. However, undergraduate medical education literature has not clearly articulated the distinctions between the roles and core responsibilities of each guidance approach. Attempts to describe each role and responsibility have generated ambiguity and steered institutions towards implementing their own role-specific functions. The purpose of this paper is to establish a functional framework that may be used to differentiate the principal duties of a mentor, coach, and advisor in the context of undergraduate medical education (UME). Four key components are necessary to achieve this goal: (1) adopting a singular definition for each form of guidance; (2) characterizing each role based on unique skills; (3) describing the interplay between learner needs and educator capabilities; (4) training educators on how to effectively distinguish each form of guidance. Creating clear distinctions between mentors, coaches, and advisors in medical education will bolster students' academic experience and improve the educator-learner relationship. These definitions may also benefit faculty members by providing a clear framework for their responsibilities, which can be used for evaluations or determining future promotions.

Repeated Prenatal Exposure to Valproic Acid Results in Auditory Brainstem Hypoplasia and Reduced Calcium Binding Protein Immunolabeling.

Auditory dysfunction is a common occurrence in individuals with autism spectrum disorder (ASD). While most cases of ASD are of unknown etiology, in utero exposure to the antiepileptic valproic acid (VPA) significantly increases risk. We have previously identified significant dysmorphology and hypoplasia in the auditory brainstem of humans with ASD and rodents exposed to VPA in utero. Further, we have identified abnormal c-Fos immunolabeling patterns after exposure to pure tone stimuli in VPA-exposed animals. Herein, we describe the impact of repeated exposure to VPA on key components of the auditory hindbrain, the ventral cochlear nucleus (VCN) and superior olivary complex (SOC). Specifically, we examined neuronal number, neuronal morphology, immunolabeling for the calcium binding proteins calbindin (CB) and calretinin (CR), dopaminergic innervation and the structure of calyx terminals in the medial nucleus of the trapezoid body (MNTB). VPA-exposed animals had significantly fewer neurons in both the VCN and SOC. VPA had a differential impact on the size of neurons in the VCN and SOC. VPA-exposed animals have reduced CB and CR immunolabeling and a lower density of dopaminergic terminals. Finally, we saw no difference in the surface area or volume of calyx terminals in the MNTB, although there was a relative increase in the surface area and volume of calyces in VPA-exposed animals. These results indicate hypotrophy of the auditory brainstem, abnormal calcium regulation and reduced dopaminergic input. Together, such alterations suggest abnormal brainstem circuitry and significant auditory dysfunction in VPA-exposed animals.

Medical mirroring: granulomatosis with polyangiitis (formerly Wegener's) mimicking immunoglobulin-G4 related disease.

Granulomatosis with polyangiitis (GPA; formerly Wegener's) can present with clinical and histopathological features similar to those of immunoglobulin-G4 related disease (IgG4-RD), a recently described fibro-inflammatory condition. The ability of these two distinct entities to mimic each other closely creates significant pitfalls in diagnosis. We present a unique case in which GPA presented as a peri-aortic fibrotic mass in the retroperitoneum. The patient's other clinical features also overlapped with classic IgG4-RD disease manifestations, but the histopathology in two organs and the serological data confirmed the diagnosis of GPA. Rigorous histopathological review remains the gold standard for the diagnosis of GPA and the distinction of this entity from IgG4-RD and other mimickers.

Squamous cell lung carcinoma presenting as melena: a case report and review of the literature.

Lung cancer has a predilection to widely metastasize to the liver, bone, brain and adrenal glands. Metastasis of primary lung tumors to the stomach is infrequent, with only sporadic cases reported. Most cases are asymptomatic and diagnosed post-mortem on autopsy. The incidence of symptomatic gastrointestinal metastases is extremely rare. Herein, we describe a case of gastric metastasis by squamous cell lung carcinoma, presenting as melena and diagnosed by esophagogastroduodenoscopy. To the best of our knowledge, only twenty other cases in the English literature have reported symptomatic gastric metastasis of lung cancer diagnosed by endoscopic biopsy. A brief review of the literature shows gastric metastasis of lung cancer to have a predilection to occur most frequently in male smokers with the most common type of tumor likely to be squamous cell carcinoma.

Isolated splenic metastasis in a patient with two distinct genitourinary malignancies.

Splenic metastasis is rare, occurring in 2.3%- 7.1% of cases, of which 95% are carcinomas.1 The lung is the most common primary tumor site (21% of cases), followed by the gastrointestinal system, breast, ovaries, and skin. In a retrospective study evaluating the clinical and pathological impact of splenic metastases during a 25-year period in China, it was found that about 5.3% of metastases were isolated splenic metastasis.2 Isolated splenic metastasis from kidney cancer is very rare and is often an incidental finding. Here we report a case with isolated splenic metastasis in a patient with both primary renal cell carcinoma and prostate cancer, which turned out to be metastatic renal cell carcinoma in the spleen.

Neuroendocrine carcinoma of the larynx with metastasis to the eyelid.

Neuroendocrine tumors are a rare type of neoplasms that comprise only 0.5% of all malignancies.¹ They usually arise from the gastrointestinal tract and the lung.¹,² Neuroendocrine carcinoma of the head and neck is a relatively rare malignancy described in the literature. The larynx is the most commonly affected region of the head and neck.³,4 Nevertheless, small-cell carcinoma comprises only 0.5% of all laryngeal cancers.5 Neuroendocrine carcinoma of the larynx carries variable prognosis depending on the histological subtype.6 Typical carcinoid rarely metastasizes, but atypical carcinoid and small-cell carcinoma have high rates of metastasis, usually in the lung and liver.² Cutaneous metastasis from neuroendocrine carcinoma is an extremely rare entity, with only few cases reported in the English literature.7,8 We report the case of an elderly man with recurrent laryngeal neuroendocrine carcinoma with metastasis to the eyelid.

Gemicitabine-induced radiation recall phenomenon in 2 distinctive sites on the same patient.

Radiation recall phenomenon is an acute inflammatory reaction that develops in previously irradiated areas after administration of inciting agents systemically. The most common agents are anticancer drugs. Gemcitabine, a fluorine-substituted deoxycytidine analog, is widely used as a chemotherapy medication. Its antitumor effect results from the blockade of DNA synthesis and DNA repair. It has been used in advanced pancreatic, non-small-cell lung, bladder, and ovarian cancers; soft-tissue sarcoma; and non-Hodgkin lymphoma. It has occasionally been reported to cause radiation recall phenomenon. The time between radiation and recall may range from weeks to almost a year.

Metastases to the thyroid presenting as a metabolically inactive incidental thyroid nodule with stable size in 15 months.

Though the thyroid gland has a rich vascular supply, incidence of metastatic disease from distant organs is rare. Here we present an unusual case of metastases to the thyroid with several interesting features. A 63-year-old male with history of adenocarcinoma of the right lobe lung (5 years prior to presentation), treated with surgery and chemotherapy, followed by new adenosquamous lung cancer in the left lobe of the lung (one year prior to presentation), treated surgically followed by adjuvant chemotherapy, was referred to Endocrinology section for evaluation of an incidental thyroid nodule on CT chest. Ultrasound (US) of the thyroid revealed a complex, predominantly hypoechoic lesion measuring 1.8 cm within the lower pole of the right thyroid lobe and a subcentimeter lesion in the left lobe of the thyroid. Review of prior CT chests showed that the lesion in the right lobe was stable for 15 months, with no evidence of a hypermetabolic lesion on PET scan. The subcentimeter lesion was not seen on prior CT scans. US guided fine needle aspiration (FNA) and pathology of the lobectomy of the thyroid confirmed adenosquamous carcinoma. Interesting features in this case are that the thyroid metastases occurred without any evidence of synchronous lesions elsewhere, the size was stable over 15 months, and the lesions were metabolically inactive.

Gemcitabine-induced gouty arthritis attacks.

In this case report, we review the experience of a patient who presented with early stage pancreatic cancer (Stage IIb) who underwent a Whipple procedure and adjuvant chemoradiation. The patient's past medical history included early stage colon cancer in remission, post-traumatic-stress-disorder, hypertension, hyperlipidemia, osteoarthritis, gout, and pre-diabetes. Chemotherapy initially consisted of weekly gemcitabine. The patient developed acute gouty attacks after his second dose of gemcitabine, which brought him to the emergency room for emergent treatment on several occasions. Gemcitabine was held and treatment began with fluorouracil and concurrent radiation. After completion of his chemoradiation with fluorouracil, he was again treated with weekly gemcitabine alone. As soon as the patient started gemcitabine chemotherapy the patient developed gouty arthritis again, requiring discontinuation of chemotherapy. The patient received no additional treatment until his recent recurrence 8 months later where gemcitabine chemotherapy was again introduced with prophylactic medications consisting of allopurinol 100 mg by mouth daily and colchicine 0.6 mg by mouth daily throughout gemcitabine chemotherapy, and no signs of gouty arthritis occurred. To our knowledge, this is the first case report describing gout attacks associated with gemcitabine therapy. There is limited data available describing the mechanism that gouty arthritis may be precipitated from gemcitabine chemotherapy. Further monitoring and management may be required in patients receiving gemcitabine chemotherapy with underlying gout.

Signaling through CD14 attenuates the inflammatory response to Borrelia burgdorferi, the agent of Lyme disease.

Lyme disease is a chronic inflammatory disorder caused by the spirochetal bacterium, Borrelia burgdorferi. In vitro evidence suggests that binding of spirochetal lipoproteins to CD14, a pattern recognition receptor expressed on monocytes/macrophages and polymorphonuclear cells, is a critical requirement for cellular activation and the subsequent release of proinflammatory cytokines that most likely contribute to symptomatology and clinical manifestations. To test the validity of this notion, we assessed the impact of CD14 deficiency on Lyme disease in C3H/HeN mice. Contrary to an anticipated diminution in pathology, CD14(-/-) mice exhibited more severe and persistent inflammation than did CD14(+/+) mice. This disparity reflects altered gene regulation within immune cells that may engender the higher bacterial burden and serum cytokine levels observed in CD14(-/-) mice. Comparing their in vitro stimulatory activity, live spirochetes, but not lysed organisms, were a potent CD14-independent stimulus of cytokine production, triggering an exaggerated response by CD14(-/-) macrophages. Collectively, our in vivo and in vitro findings support the provocative notion that: 1) pattern recognition by CD14 is entirely dispensable for elaboration of an inflammatory response to B. burgdorferi, and 2) CD14-independent signaling pathways are inherently more destructive than CD14-dependent pathways. Continued study of CD14-independent signaling pathways may provide mechanistic insight into the inflammatory processes that underlie development of chronic inflammation.