Microbial Influences on Immune Checkpoint Inhibitor Response in Melanoma: The Interplay between Skin and Gut Microbiota.

Immunotherapy has revolutionized the treatment of melanoma, but its limitations due to resistance and variable patient responses have become apparent. The microbiota, which refers to the complex ecosystem of microorganisms that inhabit the human body, has emerged as a promising area of research for its potential role in melanoma development and treatment response. Recent studies have highlighted the role of microbiota in influencing the immune system and its response to melanoma, as well as its influence on the development of immune-related adverse events associated with immunotherapy. In this article, we discuss the complex multifactorial mechanisms through which skin and gut microbiota can affect the development of melanoma including microbial metabolites, intra-tumor microbes, UV light, and the immune system. In addition, we will discuss the pre-clinical and clinical studies that have demonstrated the influence of different microbial profiles on response to immunotherapy. Additionally, we will explore the role of microbiota in the development of immune-mediated adverse events.

The impact of young age (< 40 years) on the outcome of a cohort of patients with primary non-metastatic breast cancer: analysis of 10-year survival of a prospective study.

BACKGROUND: The role of young age (< 40 years) at diagnosis as an independent risk factor for adverse outcomes in female patients with breast cancer has been highlighted in several studies. In this prospective study, we assessed the difference in 10-year survival between two groups of patients diagnosed with non-metastatic breast cancer based on an age cutoff of 40 years. We also assessed the impact of factors including tumor characteristics, molecular markers and immunohistochemical markers on survival outcomes, highlighting the interaction of those variables with age. METHODS: A total of 119 female patients with newly diagnosed non-metastatic breast cancer were recruited at the American University of Beirut Medical Center (AUBMC) between July 2011 and May 2014. Patients were recruited and divided into 2 age groups (< 40 and ≥ 40 years). In addition to clinical characteristics, we assessed immunohistochemistry including estrogen, progesterone and HER2 receptors, p53, cyclin B1, vascular endothelial growth factor receptor (VEGFR), and ki-67. Germline BRCA mutations were also performed on peripheral blood samples. Patient and tumor characteristics were compared between the age groups. 10-year overall survival (OS) and disease-free survival (DFS) were estimated accordingly. Cox regression analysis was performed in order to assess the effect of the different variables on clinical outcomes. RESULTS: After a median Follow-up of 96 (13-122) months, the estimated 10-year OS was 98.6% for patients ≥40 as compared to 77.6% in patients < 40 (p = 0.001). A similar trend was found for 10-year DFS reaching 90% for patients ≥40 and 70.4% for those < 40 (p = 0.004). On multivariate analysis for DFS and OS, only younger age (< 40 years), higher stage and triple negative phenotype among other parameters assessed significantly affected the outcome in this cohort. CONCLUSION: This prospective study confirms the association between younger age and adverse survival outcomes in patients with non-metastatic breast cancer. Future studies of the whole genome sequences may reveal the genomic basis underlying the clinical differences we have observed.

A phase II single arm study of Nivolumab with stereotactic Ablative radiation Therapy after induction chemotherapy in CHOlangiocarcinoma (NATCHO).

BACKGROUND: Intrahepatic cholangiocarcinoma (CCA) is amongst the most common primary liver tumors worldwide. CCA carries a bad prognosis prompting research to establish new treatment modalities other than surgery and the current chemotherapeutic regimens adopted. Hence, this trial explores a new therapeutic approach, to combine stereotactic body radiation therapy (SBRT) and immunotherapy (Nivolumab), and asses its clinical benefit and safety profile after induction chemotherapy in CCA. METHODOLOGY: This is a Phase II open-label, single-arm, multicenter study that investigates Nivolumab (PD-1 inhibitor) treatment at Day 1 followed by SBRT (30 Gy in 3 to 5 fractions) at Day 8, then monthly Nivolumab in 40 patients with non-resectable locally advanced, metastatic or recurrent intrahepatic or extrahepatic CCA. Eligible patients were those above 18 years of age with a pathologically and radiologically confirmed diagnosis of non-resectable locally advanced or metastatic or recurrent intrahepatic or extrahepatic CCA, following 4 cycles of cisplatin-based chemotherapy with an estimated life expectancy of more than 3 months, among other criteria. The primary endpoint is the progression free survival (PFS) rate at 8 months and disease control rate (DCR). The secondary endpoints are overall survival (OS), tumor response rate (TRR), duration of response, evaluation of biomarkers: CD3 + , CD4 + and CD8 + T cell infiltration, as well as any change in the PD-L1 expression through percutaneous core biopsy when compared with the baseline biopsy following 1 cycle of Nivolumab and SBRT. DISCUSSION: SRBT alone showed promising results in the literature by both inducing the immune system locally and having abscopal effects on distant metastases. Moreover, given the prevalence of PD-L1 in solid tumors, targeting it or its receptor has become the mainstay of novel immunotherapeutic drugs use. A combination of both has never been explored in the scope of CCA and that is the aim of this study. TRIAL REGISTRATION: ClinicalTrials.gov NCT04648319 , April 20, 2018.

Metabolic Syndrome: Updates on Pathophysiology and Management in 2021.

Metabolic syndrome (MetS) forms a cluster of metabolic dysregulations including insulin resistance, atherogenic dyslipidemia, central obesity, and hypertension. The pathogenesis of MetS encompasses multiple genetic and acquired entities that fall under the umbrella of insulin resistance and chronic low-grade inflammation. If left untreated, MetS is significantly associated with an increased risk of developing diabetes and cardiovascular diseases (CVDs). Given that CVDs constitute by far the leading cause of morbidity and mortality worldwide, it has become essential to investigate the role played by MetS in this context to reduce the heavy burden of the disease. As such, and while MetS relatively constitutes a novel clinical entity, the extent of research about the disease has been exponentially growing in the past few decades. However, many aspects of this clinical entity are still not completely understood, and many questions remain unanswered to date. In this review, we provide a historical background and highlight the epidemiology of MetS. We also discuss the current and latest knowledge about the histopathology and pathophysiology of the disease. Finally, we summarize the most recent updates about the management and the prevention of this clinical syndrome.

Metabolic Factors Affecting Tumor Immunogenicity: What Is Happening at the Cellular Level?

Immunotherapy has changed the treatment paradigm in multiple solid and hematologic malignancies. However, response remains limited in a significant number of cases, with tumors developing innate or acquired resistance to checkpoint inhibition. Certain "hot" or "immune-sensitive" tumors become "cold" or "immune-resistant", with resultant tumor growth and disease progression. Multiple factors are at play both at the cellular and host levels. The tumor microenvironment (TME) contributes the most to immune-resistance, with nutrient deficiency, hypoxia, acidity and different secreted inflammatory markers, all contributing to modulation of immune-metabolism and reprogramming of immune cells towards pro- or anti-inflammatory phenotypes. Both the tumor and surrounding immune cells require high amounts of glucose, amino acids and fatty acids to fulfill their energy demands. Thus, both compete over one pool of nutrients that falls short on needs, obliging cells to resort to alternative adaptive metabolic mechanisms that take part in shaping their inflammatory phenotypes. Aerobic or anaerobic glycolysis, oxidative phosphorylation, tryptophan catabolism, glutaminolysis, fatty acid synthesis or fatty acid oxidation, etc. are all mechanisms that contribute to immune modulation. Different pathways are triggered leading to genetic and epigenetic modulation with consequent reprogramming of immune cells such as T-cells (effector, memory or regulatory), tumor-associated macrophages (TAMs) (M1 or M2), natural killers (NK) cells (active or senescent), and dendritic cells (DC) (effector or tolerogenic), etc. Even host factors such as inflammatory conditions, obesity, caloric deficit, gender, infections, microbiota and smoking status, may be as well contributory to immune modulation, anti-tumor immunity and response to immune checkpoint inhibition. Given the complex and delicate metabolic networks within the tumor microenvironment controlling immune response, targeting key metabolic modulators may represent a valid therapeutic option to be combined with checkpoint inhibitors in an attempt to regain immune function.

The Role of Gut Microbiota in Overcoming Resistance to Checkpoint Inhibitors in Cancer Patients: Mechanisms and Challenges.

The introduction of immune checkpoint inhibitors has constituted a major revolution in the treatment of patients with cancer. In contrast with the traditional cytotoxic therapies that directly kill tumor cells, this treatment modality enhances the ability of the host's immune system to recognize and target cancerous cells. While immune checkpoint inhibitors have been effective across multiple cancer types, overcoming resistance remains a key area of ongoing research. The gut microbiota and its role in cancer immunosurveillance have recently become a major field of study. Gut microbiota has been shown to have direct and systemic effects on cancer pathogenesis and hosts anti-tumor immune response. Many studies have also shown that the host microbiota profile plays an essential role in the response to immunotherapy, especially immune checkpoint inhibitors. As such, modulating this microbial environment has offered a potential path to overcome the resistance to immune checkpoint inhibitors. In this review, we will talk about the role of microbiota in cancer pathogenesis and immune-system activity. We will also discuss preclinical and clinical studies that have increased our understanding about the roles and the mechanisms through which microbiota influences the response to treatment with immune checkpoint inhibitors.

Thrombotic Microangiopathy in the Setting of Colorectal Cancer: A Therapeutic Challenge with a Bad Prognosis.

While most cases of thrombotic microangiopathic hemolytic anemias are idiopathic, some can occur in the setting of a malignancy. Differentiating both conditions is crucial to initiate the appropriate treatment. In this case report and literature review, we discuss the occurrence of a thrombotic microangiopathy in a 61-year-old male patient with a treatment-refractory metastatic colorectal cancer invading his bone marrow. Plasmapheresis does not constitute the mainstay of treatment in this setting, as targeting the primary disease is the ultimate management. Treating the condition of our patient has been challenging as multiple lines of treatments of his primary disease had been exhausted. The discrepancy in KRAs status obtained between PCR and later NGS offered a new treatment line with Cetuximab. In this article, we will discuss the different factors that differentiate between idiopathic and cancer-induced microangiopathy. We will emphasize on the fact that the treatment of the primary disease constitutes the most important step in the treatment of cancer-induced thrombotic microangiopathy. We will also raise several explanations to target the disagreement in KRAS status obtained by the different technical modalities.

Insights of Medical Students and Graduates Toward Electronic Learning During the COVID-19 Pandemic in Lebanon: A National Cross-Sectional Study.

OBJECTIVE: This study examines the perceptions of Lebanese medical students and graduates regarding the switch to electronic learning (e-learning) and measures their psychological distress amid the COVID-19 pandemic, compounded by an unprecedented financial collapse and the August 4 Beirut blast. METHODS: This is a national cross-sectional descriptive study, consisting of a 48-item questionnaire, diffused online to Lebanese medical students between February 8 and 21, 2021. The survey divided into 5 sections assesses for (1) Sociodemographic information, (2) implemented changes in medical education delivery precipitated by the pandemic, (3) students' perceptions regarding the effectiveness, advantages, and barriers of e-learning, and (4) role of e-learning in clinical training. Finally, students' psychological distress was measured, using the Kessler 10-item distress scale (K10). Descriptive analyses were performed using Stata version 13 and Excel. RESULTS: 1060 responses were recorded (27% response rate) across all Lebanese medical schools. Although 71.6% of participants found e-learning to be stimulating, half of the participants thought it was not equally effective to face-to-face learning. Around 73.1% of students felt they were not able to learn hands-on clinical skills. Lebanese students identified cost savings (food, transportation etc) and poor internet connectivity are the most common advantage and barrier, respectively; 77.8% of participants showed high/very high levels of distress (K10 score ≥22). CONCLUSIONS: Ensuring accessibility and availability of resources such as electricity and internet is of utmost priority. Lebanese medical schools need to incorporate clinical training experiences to their virtual platforms to maintain the quality of medical education to their students. A particular attention to students' mental health is warranted, by increasing awareness and access to mental health services.

Systemic AL amyloidosis: current approach and future direction.

Systemic Light chain (AL) amyloidosis is a monoclonal plasma cell proliferative disorder characterized by deposition of amyloidogenic monoclonal light chain fragments causing organ dysfunction. It is a fatal disease and if not diagnosed and treated early can lead to organ failure and potentially death. The renal system along with the cardiovascular system are the most common organs involved but other organs such as gut and liver can be involved as well. The initial evaluation of patients requires confirming the diagnosis with tissue biopsy and staining with Congo red followed by confirmatory typing with mass spectrometry of the Congo red positive tissue. Then establishing the extent of the organs involvement by various staging and biomarkers testing. The treatment options and the tolerability of therapy depend on the disease staging, frailty, and co-morbidities. The autologous hematopoietic cell transplantation (HCT) after high dose melphalan therapy is an effective strategy which is usually done after initial bortezomib induction therapy. Unfortunately, most systemic AL amyloidosis patients are not candidate for HCT due to frailty, old age, multi-organ involvement, renal and heart failure at the time of diagnosis. While it is widely accepted that the patients need to be treated until they achieve complete hematologic response, the maintenance therapy after HCT is not well established in AL amyloidosis. In this review, we report the literature on the latest treatment updates of AL amyloidosis and the ongoing clinical trials highlighting the future treatments.

Fertility in multiple recurrent bilateral ovarian teratomas: A case report.

Very few cases of bilateral and recurrent teratomas have been reported. We present the case of a 21-year-old nulliparous female who presented to an outside facility complaining of left flank pain and was found to have bilateral ovarian teratomas. The physician proceeded with a laparotomy. Five years later, the patient presented to our facility complaining of abdominal pain. Imaging revealed a second incidence of bilateral dermoid cysts for which she underwent a bilateral laparoscopic cystectomy. The patient retained her fertility and was able to deliver a newborn 2 years later. At the age of 31, and during a regular check-up, the patient was found again to have a third incidence of bilateral dermoid cysts for which she underwent bilateral laparoscopic cystectomy with preservation of her ovaries. In conclusion, laparoscopic removal of dermoid cysts is of utmost importance to retain the fertility of young patients. Regular check-up by ultrasound post-operatively is necessary to screen for recurrences and prevent painful presentations.

Everolimus in poorly differentiated neuroendocrine carcinoma of unknown primary: A case report.

Malignancies with unknown primaries contribute to a small yet significant percentage of overall tumors. Neuroendocrine carcinomas, a rare disease with a poor prognosis, have been known to present as an unknown primary. Treatment consists of cytotoxic chemotherapy but given the latter's high toxicity profile new treatment options are being explored. In this case report, we describe a case of a patient with poorly differentiated neuroendocrine carcinoma of unknown primary treated with compassionate oral everolimus after his refusal of intravenous chemotherapy.

From Tumor Cells to Endothelium and Gut Microbiome: A Complex Interaction Favoring the Metastasis Cascade.

Metastasis is a complicated process through which tumor cells disseminate to distant organs and adapt to novel tumor microenvironments. This multi-step cascade relies on the accumulation of genetic and epigenetic alterations within the tumor cells as well as the surrounding non-tumor stromal cells. Endothelial cells constitute a major player in promoting metastasis formation either by inducing the growth of tumor cells or by directing them towards dissemination in the blood or lymph. In fact, the direct and indirect interactions between tumor and endothelial cells were shown to activate several mechanisms allowing cancer cells' invasion and extravasation. On the other side, gastrointestinal cancer development was shown to be associated with the disruption of the gut microbiome. While several proposed mechanisms have been investigated in this regard, gut and tumor-associated microbiota were shown to impact the gut endothelial barrier, increasing the dissemination of bacteria through the systemic circulation. This bacterial dislocation allows the formation of an inflammatory premetastatic niche in the distant organs promoting the metastatic cascade of primary tumors. In this review, we discuss the role of the endothelial cells in the metastatic cascade of tumors. We will focus on the role of the gut vascular barrier in the regulation metastasis. We will also discuss the interaction between this vascular barrier and the gut microbiota enhancing the process of metastasis. In addition, we will try to elucidate the different mechanisms through which this bacterial dislocation prepares the favorable metastatic niche at distant organs allowing the dissemination and successful deposition of tumor cells in the new microenvironments. Finally, and given the promising results of the studies combining immune checkpoint inhibitors with either microbiota alterations or anti-angiogenic therapy in many types of cancer, we will elaborate in this review the complex interaction between these 3 factors and their possible therapeutic combination to optimize response to treatment.

Single Cell RNA Sequencing: A New Frontier in Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma is a malignancy with a high mortality rate. It exhibits significant heterogeneity in metabolic pathways which are associated with its progression. In this review, we discuss the role of single cell RNA sequencing in unraveling the metabolic and clinical features of these highly malignant tumors.

The Gut Microbiome and Alzheimer's Disease: A Growing Relationship.

Evidence that the gut microbiota plays a key role in the pathogenesis of Alzheimer's disease is already un-ravelling. The microbiota-gut-brain axis is a bidirectional communication system that is not fully understood but includes neural, immune, endocrine, and metabolic pathways. The progression of Alzheimer's disease is supported by mechanisms related to the imbalance in the gut microbiota and the development of amyloid plaques in the brain, which are at the origin of Alzheimer's disease. Alterations in the composition of the gut microbiome led to dysregulation in the pathways governing this system. This leads to neurodegeneration through neuroinflammation and neurotransmitter dysregulation. Neurodegeneration and disruption of the blood-brain barrier are frontiers at the origin of Alzheimer's disease. Furthermore, bacteria populating the gut microbiota can secrete large amounts of amyloid proteins and lipopolysaccharides, which modulate signaling pathways and alter the production of proinflammatory cytokines associated with the pathogenesis of Alz-heimer's disease. Importantly, through molecular mimicry, bacterial amyloids may elicit cross-seeding of misfolding and induce microglial priming at different levels of the brain-gut-microbiota axis. The potential mechanisms of amyloid spreading include neuron-to-neuron or distal neuron spreading, direct blood-brain barrier crossing, or via other cells such as astrocytes, fibroblasts, microglia, and immune system cells. Gut microbiota metabolites, including short-chain fatty acids, pro-inflammatory factors, and neurotransmitters may also affect AD pathogenesis and associated cognitive decline. The purpose of this review is to summarize and discuss the current findings that may elucidate the role of gut microbiota in the development of Alzheimer's disease. Understanding the underlying mechanisms may provide new insights into novel therapeutic strategies for Alzheimer's disease, such as probiotics and targeted oligosaccharides.

Pathophysiology, clinical findings, and management of Fox-Fordyce disease: A systematic review.

BACKGROUND: Fox-Fordyce (FFD), also known as apocrine military, is an uncommon chronic inflammation of the apocrine sweat glands. It is characterized by pruritic, papular eruptions in apocrine-gland-bearing regions. FFD was described a century ago, but the exact pathogenesis of the disease and the management are not well understood. AIMS: This paper provides a wide understanding of the pathophysiology, clinical findings, and management of Fox-Fordyce disease. Its aim is to help the physician to diagnose and manage this entity accordingly. METHODS: A research was done using PubMed database on 12 April 12, 2020, and in order to retrieve all case reports, case series, cohort studies, randomized, and nonrandomized clinical trials were included describing FFD among patients. RESULTS: A total of 43 articles and 68 patients were included in the study. The majority of patients were young females. The disease was bilateral in 90%, affected the axillae and to a lesser extent the pubic and the periareolar areas and rarely the thoracic area, the abdominal area, and the face. FFD followed a relapsing and remitting course, and an evident improvement in disease course was noted after menopause. CONCLUSION: The typical FFD patient is a post-pubertal female and pre-menopause, presenting with pruritic papules in apocrine-gland-bearing regions. FFD can be sporadic or occurs in family, and it can be asymptomatic in 1/(3-4) of patients and can be triggered by laser hair removal and hormonal changes. Further randomized clinical trials assessing different treatment of FFD are now warranted.

Comparison Between Liver Stiffness Measurement by Fibroscan and Splenic Volume Index as NonInvasive Tools for the Early Detection of Oxaliplatin-induced Hepatotoxicity.

Background: Oxaliplatin remains an essential component of many chemotherapy protocols for gastrointestinal cancers; however, neurotoxicity and hepatotoxicity may be dose-limiting. The gold standard for the diagnosis of oxaliplatin-induced hepatotoxicity is liver biopsy, which is invasive and costly. Splenomegaly has also been used as a surrogate for liver biopsy in detecting oxaliplatin-induced sinusoidal obstruction syndrome (SOS), but splenic measurement is not routine and can be inaccurate and complex. We investigated the correlation between increased liver elasticity assessed by Fibroscan and the increase in spleen volume on cross-sectional imaging after oxaliplatin as a noninvasive technique to assess liver stiffness associated with oxaliplatin-induced SOS. Methods: Forty-six patients diagnosed with gastrointestinal cancers and planned to take oxaliplatin containing regimens were included in this prospective study at the American University of Beirut Medical Center (AUBMC). Measurement of spleen volume using cross-sectional imaging and of liver elasticity using Fibroscan was performed at baseline, 3 and 6 months after starting oxaliplatin. Mean liver elasticity measurements were compared between patients stratified by the development of splenomegaly using the Student t-test. Splenomegaly was defined as 50% increase in spleen size compared with baseline. Results: Patients who developed splenomegaly after oxaliplatin use had significantly higher mean elasticity measurements as reported by Fibroscan at 3 (16.2 vs. 7.8 kPa, P = 0.036) and 6 (9.3 vs. 6.7 kPa, P = 0.03) months. Conclusion: Measurement of elasticity using Fibroscan could be potentially used in the future as a noninvasive test for predicting oxaliplatin-induced hepatotoxicity.

Complete Radiological Response of Recurrent Metastatic Adrenocortical Carcinoma to Pembrolizumab and Mitotane.

Adrenocortical carcinoma (ACC) is a rare malignancy with a poor prognosis. Treatment options for ACC are limited, with resection the main intervention. Most cases present in late metastatic cases, and data regarding effective therapies is limited. We report a case of ACC in a 40-year-old woman with history of ACC postadrenalectomy, who presented with recurrent metastatic ACC in the left perinephric space. She was started on pembrolizumab which was added to her mitotane maintenance therapy. Complete radiological response was achieved after 4 cycles of pembrolizumab. As far as we know, this is the first case to achieve complete radiological response with mitotane and pembrolizumab in recurrent metastatic ACC, with negative prognostic markers and no prior radiotherapy. As our findings are in the setting of one clinical case, we suggest the need to perform a trial to assess the benefit of combining mitotane and pembrolizumab in treating metastatic ACC.

Management of colorectal cancer in the era of COVID-19: Challenges and suggestions.

The Coronavirus (COVID-19) pandemic had a huge impact on all sectors around the world. In particular, the healthcare system has been subject to an enormous pressure that has surpassed its ability in many instances. Additionally, the pandemic has called for a review of our daily medical practices, including our approach to colorectal cancer management where treatment puts patients at high risk of virus exposure. Given their higher median age, patients are at an increased risk for severe symptoms and complications in cases of infection, especially in the setting of immunosuppression. Therefore, a review of the routine colorectal cancer practices is needed to minimize risk of exposure. Oncologists should weigh risk of exposure versus the patient's oncologic benefits when approaching management. In addition, treatment protocols should be modified to minimize hospital visits and admissions while maintaining the same treatment efficacy. In this review, we will focus on challenges that colorectal cancer patients face during the pandemic, while highlighting the priority in each case. We will also discuss the evidence for potential modifications to existing treatment plans that could reduce infectious exposure without compromising care. Finally, we will discuss the impact of the socio-economic difficulties faced by Lebanese patients due to a poor economy toppled by an unexpected pandemic.

Neurobrucellosis: Brief Review.

BACKGROUND: Brucella are small, nonmotile, intracellular, and aerobic gram-negative bacteria. Of the 10 species that currently form the genus Brucella, 5 were shown to be pathogenic in humans. REVIEW SUMMARY: The epidemiology, clinical manifestations, diagnosis and imaging, and treatment of neurobrucellosis will be reviewed.Brucellosis's transmission to humans occurs by direct contact with contaminated animals. Older patients are at increased risk of nervous system involvement in brucellosis. Brucella spp. can lead to central nervous system involvement through direct damage via invasion of neural tissue or indirect damage caused by endotoxins or immune inflammatory reactions elicited by the presence of the bacteria in the body. Patients can have general nonspecific symptoms in addition to neurological and psychiatric symptoms. There are 4 diagnostic criteria for the diagnosis of neurobrucellosis, which include signs and symptoms suggestive of neurobrucellosis, a positive finding of Brucella spp. in the cerebrospinal fluid (CSF), and/or a positive titer of antibodies targeting brucella in the CSF, lymphocytosis with high protein levels and low glucose levels in CSF, and imaging findings (either cranial magnetic resonance imaging or computed tomography) peculiar to neurobrucellosis. For the treatment, a combined therapy is favored over monotherapy for the eradication of Brucella. Moreover, a multirouted therapy has been associated with increased treatment efficacy. The prognosis of neurobrucellosis is dependent on patients' clinical presentation: brucellar meningitis is associated with a good prognosis, whereas diffuse central nervous system involvement is associated with the development of long-term sequelae. CONCLUSIONS: Neurobrucellosis affects patients globally and in endemic areas. Neurologists should familiarize themselves with its clinical presentation, diagnosis, and treatment to provide optimal care for their patients.

Total neoadjuvant therapy in patients with locally advanced rectal cancer: A tertiary medical center experience.

The current standard of care for locally advanced rectal cancer (LARC) includes preoperative chemoradiation, followed by total mesorectal excision and adjuvant chemotherapy. This multimodality treatment improves local control but is associated with low compliance rates without clear beneficial effects on overall survival (OS) and distant metastasis. In this retrospective study, the charts of patients diagnosed with cT3/4 or cT2-node-positive rectal cancer between January 2011 and June 2019 were reviewed. The chemoradiation therapy (CRT) group received a long course of CRT with capecitabine followed by surgery and adjuvant chemotherapy. The total neoadjuvant therapy (TNT) group received 6 cycles mFOLFOX and a short course of radiation therapy followed by surgery. A total of 81 patients were included, among which 55 (67.9%) received CRT and 26 (32.1%) received TNT. In the CRT group, 15 (27.3%) patients achieved pathologic complete response (pCR) compared with 10 (38.5%) in the TNT group (P=0.22). A total of 19 (35.8%) cases in the CRT group downstaged to pT0N0 or pT1N0 compared with 11 (42.3%) in the TNT group (P=0.33). The 2-year disease-free survival (DFS) rate was 81.0% in the TNT group and 84.0% in the CRT group (P=0.15). Out of 55 patients in the CRT group, 30 patients received adjuvant chemotherapy, 22 (40.0% of CRT cases) of which completed a full course. All 26 patients in the TNT group received neoadjuvant chemotherapy, where 22 (84.6%) patients took a full course (P<0.001). In conclusion, the present study revealed that patients treated with TNT were more compliant to chemotherapy than those treated with CRT. A numerically higher pCR rate, and nodal and tumor downstaging were noted in the TNT group without significance. No difference was noted in the 2-year DFS. Longer follow-up is required.