Supplement Use and Increased Risks of Cancer: Unveiling the Other Side of the Coin.

There is a rising trend in the consumption of dietary supplements, especially among adults, with the purpose of improving health. While marketing campaigns tout the potential health benefits of using dietary supplements, it is critical to evaluate the potential harmful effects associated with these supplements as well. The majority of the scarce research on the potential harmful effects of vitamins focuses on the acute or chronic toxicities associated with the use of dietary supplements. Quality research is still required to further investigate the risks of long-term use of dietary supplements, especially the risk of developing cancers. The present review concentrates on studies that have investigated the association between the risk of developing cancers and associated mortality with the risk of dietary supplements. Such an association has been reported for several vitamins, minerals, and other dietary supplements. Even though several of these studies come with their own shortcomings and critics, they must draw attention to further investigate long-term adverse effects of dietary supplements and advise consumers and healthcare providers to ponder the extensive use of dietary supplements.

A case report of challenges in distinguishing gastroesophageal junction hepatoid adenocarcinoma from testicular germ cell tumor: Insights for improved diagnosis with gene expression profiling.

Gastroesophageal junction hepatoid adenocarcinoma is a rare form of gastroesophageal cancer. We present a case of a 38-year-old man with no significant medical history who was diagnosed with gastroesophageal junction hepatoid adenocarcinoma but initially misdiagnosed with a testicular germ cell tumor, given the elevated alpha-feto protein and poorly differentiated pathology. We will elaborate on the importance of gene expression profiling in modern oncology to better define the tumor of origin in patients with cancer of unknown primary origin, how it helped us to diagnose gastroesophageal junction hepatoid adenocarcinoma and how it can help identify potential additional therapeutic targets in some cases. Due to the rarity of this subtype of gastroesophageal junction cancer there is a lack of standard therapeutic options, and we will discuss the most commonly used treatment regimens. The patient underwent three lines of antineoplastic therapy and unfortunately passed after 51 weeks of follow-up.

A comparative study of spinal cord compression management in metastatic prostate cancer: Teaching versus non-teaching hospitals in the United States.

BACKGROUND: Spinal cord compression (SCC) in metastatic prostate cancer (MPC) is a critical complication and multiple factors influence the optimal therapeutic strategy. We investigated the differences in practice patterns between teaching hospitals (TH) and non-teaching hospitals (NTH) across the United States. METHOD: Using the National Inpatient Sample Database (NIS), we performed a retrospective study on hospitalizations with MPC and SCC between 2016 and 2020 in US. We compared demographic factors, comorbidities, treatment modalities, duration of hospitalization, financial expenditures, and mortality between TH and NTH. We also examined the patients' characteristics and outcomes in TH and NTH based on their chosen therapeutic strategy. RESULTS: We identified 11,380 admissions with metastatic prostate cancer and SCC; 9610 in TH and 1770 in NTH. The median cost of hospitalization was $21,922 in TH and $15,141 in NTH. Although the median age and Charlson comorbidity score did not differ between two groups, patients in TH were more likely to receive intervention (radiation or surgery) compared to NTH (Surgery: 28.2% in TH vs. 23.0% in NTH & Radiation: 12.1% in TH vs. 8.2% in NTH). Mortality was lower in TH than NTH (4.5% vs. 7.9%). In both TH and NTH, a higher proportion of patients with private insurance underwent surgery (TH: Surgery 25.1% vs. Radiation 18.8% & NTH: Surgery 27.0% vs. 6.9%). Black patients were more likely to receive radiation than surgery in TH (34.2% vs. 26.8%). CONCLUSION: This study showed a greater percentage of patients underwent surgical intervention at TH compared to NTH. Additionally, the type of insurance and racial background were associated with distinctive treatment approaches.

Prostate Cancer in Sexual Minorities: Epidemiology, Screening and Diagnosis, Treatment, and Quality of Life.

Prostate cancer has the highest incidence among all cancers in men. Sexual minorities, including gay and bisexual men, as well as transgender, were previously a "hidden population" that experienced prostate cancer. Although there continues to remain a paucity of data in this population, analyses from studies do not reveal whether this population is more likely to endure prostate cancer. Nonetheless, several qualitative and quantitative studies have established worse quality-of-life outcomes for sexual minorities following prostate cancer treatment. Increased awareness of this previously "hidden population" among healthcare workers, as well as more research, is warranted to gain further understanding on potential disparities faced by this growing population.

Comparison of Carboplatin With Cisplatin in Small Cell Lung Cancer in US Veterans.

Importance: The current standard of care for the treatment of small cell lung cancer (SCLC) is concurrent chemoradiation for patients with limited-stage SCLC (LS-SCLC) and chemoimmunotherapy for extensive-stage SCLC (ES-SCLC). The backbone of chemotherapy regimens in both is a platinum-etoposide doublet: cisplatin is traditionally the preferred platinum agent in the curative intent setting, whereas carboplatin is preferred in ES-SCLC because of its favorable toxicity profile. Objective: To determine whether cisplatin is associated with better survival outcomes than carboplatin in treating LS-SCLC and ES-SCLC. Design, Setting, and Participants: In this cohort study, data were compiled from the National Veterans Affairs Central Cancer Registry for patients with SCLC who received platinum-based multiagent chemotherapy between 2000 and 2020 for ES-SCLC and 2000 and 2021 for LS-SCLC. Only patients with pathologically confirmed cases of LS-SCLC who received concurrent chemoradiation and ES-SCLC who received chemotherapy were included. Main Outcomes and Measures: The primary end point was overall survival (OS). The secondary end points included OS by Eastern Cooperative Oncology Group performance status, age, and laterality. Interval-censored Weibull and Cox proportional hazard regression models were used to estimate median OS and hazard ratios (HRs), respectively. Survival curves were compared by a Wald test. Results: A total of 4408 SCLC cases were studied. Most patients were White (3589 patients [81.4%]), male (4252 [96.5%]), and non-Hispanic (4142 [94.0%]); 2262 patients (51.3%) were 60 to 69 years old, followed by 1476 patients (33.5%) aged 70 years or older, 631 patients (14.3%) aged 50 to 59 years, and 39 patients (0.9%) aged 30 to 49 years. Among 2652 patients with ES-SCLC, 2032 were treated with carboplatin-based therapy and 660 received cisplatin; the median OS was 8.45 months (95% CI, 7.75-9.20 months) for cisplatin and 8.51 months (95% CI, 8.07-8.97 months) for carboplatin (HR, 1.01; 95% CI, 0.91-1.12; P = .90). Subset analysis showed no survival difference between the 2 agents in different age or performance status groups except for patients aged 70 years and older, for whom the median OS was 6.36 months (95% CI, 5.31-7.56 months) for cisplatin and 8.47 months (95% CI, 7.79-9.19 months) for carboplatin (HR, 0.77; 95% CI, 0.61-0.96; P = .02). Multivariable analysis of performance status and age did not show a significant difference in survival between the 2 groups (HR, 0.96; 95% CI, 0.83-1.10; P = .54). Of 1756 patients with LS-SCLC, 801 received carboplatin, and 1018 received cisplatin. The median OS was 26.92 months (95% CI, 25.03-28.81 months) for cisplatin and 25.58 months (95% CI, 23.64-27.72 months) for carboplatin (HR, 1.04; 95% CI, 0.94-1.16; P = .46). The median OS was not significantly different between 2 agents according to cancer stage (I-III), performance status, and age groups. A multivariable analysis of factors associated with OS accounting for stage (I-III), performance status, and age did not demonstrate a significant difference in survival between carboplatin and cisplatin in patients with LS-SCLC (HR, 0.995; 95% CI, 0.86-1.15; P = .95). Conclusions and Relevance: Cisplatin is not associated with a survival advantage over carboplatin among patients with either ES-SCLC or LS-SCLC, irrespective of performance status and age. The favorable toxicity profile of carboplatin and comparable OS support its use in both LS-SCLC and ES-SCLC in clinical practice and may allow more room for combination with novel treatment strategies in clinical trials.

Binocular Diplopia: An Unusual Presentation of Squamous Cell Carcinoma of the Lung.

Here, we discuss the case of a 72-year-old male with a known history of COPD who presented with one month of binocular diplopia and headache. The initial clinical investigation discovered destructive intraosseous lesions within the sellar and para-sellar (SPS) regions, suggesting primary versus metastatic intracranial lesions. Further examination revealed a mass in the right lung, with subsequent biopsy confirming squamous cell carcinoma (SCC) of the lung as the primary site of malignancy. The SPS regions of the basicranium, while well-documented to be associated with various primary neoplasms, rarely serve as sites of metastasis. Throughout this article, we will review the pathophysiology of squamous cell lung cancer, current understandings of SPS metastasis, and considerations of metastatic lung SCC management.

A Resident-driven Quality Improvement Project to Increase Primary Care Follow-up after Congestive Heart Failure Exacerbation: Use of a Quality and Safety Award.

OBJECTIVES: Congestive heart failure (CHF) is the most common cause of 30-day inpatient readmission. Studies have found that early follow-up with primary care physicians (PCP) within 7 days of discharge may improve 30-day readmission rates; however, many have used a multidisciplinary discharge coordination team, which is not a resource at all centers. Here, the authors present a resident-driven quality improvement initiative using a monthly quality and safety award to increase early PCP follow-up for veterans discharged following admissions due to a CHF exacerbation. Primary outcomes were percentage of PCP follow-up within 7 days and median time to PCP follow-up. Secondary outcomes included percentage of patients attending a PCP visit within 7 days, 30-day readmission, and 30-day mortality. METHODS: This prepost quasi-experimental cohort study evaluated 3 concurrent quality improvement interventions to increase PCP follow-up after CHF exacerbation. Process maps and Ishikawa diagrams examined the discharge process. Interventions included a standardized discharge scheduling order, monthly education on the process, and monthly aggregated performance feedback for each medical resident. A patient safety and quality award was given to the team with the highest rate of PCP appointments scheduled within 7 days. Patient characteristics and outcomes were gathered for a 6-month historic period and 6-month intervention period. Test of proportions and Wilcoxon Rank-Sum test were used to compare groups. RESULTS: A total of 294 patients were discharged (161 in historic group and 133 in intervention group). Appointments scheduled within 7 days of discharge increased from 43% to 79% ( P < 0.001). Median time to PCP follow-up decreased from 8 to 6 days ( P < 0.001). Patients who completed (showed up to) a PCP appointment within 7 days increased from 16% to 41% ( P < 0.001). There was no impact on 30-day readmission or mortality; however, the number of study subjects was too small to rule out an effect. CONCLUSIONS: A standardized discharge scheduling order, more robust resident education, and a monthly patient safety and quality award resulted in a significant increase in the rate of primary care follow-up within 7 days of CHF exacerbation.

Lipid metabolism reprogramming in renal cell carcinoma.

Metabolic reprogramming is recognized as a hallmark of cancer. Lipids are the essential biomolecules required for membrane biosynthesis, energy storage, and cell signaling. Altered lipid metabolism allows tumor cells to survive in the nutrient-deprived environment. However, lipid metabolism remodeling in renal cell carcinoma (RCC) has not received the same attention as in other cancers. RCC, the most common type of kidney cancer, is associated with almost 15,000 death in the USA annually. Being refractory to conventional chemotherapy agents and limited available targeted therapy options has made the treatment of metastatic RCC very challenging. In this article, we review recent findings that support the importance of synthesis and metabolism of cholesterol, free fatty acids (FFAs), and polyunsaturated fatty acids (PUFAs) in the carcinogenesis and biology of RCC. Delineating the detailed mechanisms underlying lipid reprogramming can help to better understand the pathophysiology of RCC and to design novel therapeutic strategies targeting this malignancy.

Rectal Invasion by Metastatic Prostate Adenocarcinoma.

In men, prostate cancer is the second most diagnosed cancer worldwide. Typical sites for metastasis include bone, lung, and liver. Prostate cancer with gastrointestinal involvement, particularly rectal, has been rarely reported in the literature. As patients with prostate cancer with rectal invasion may present with symptoms similar to those of other gastrointestinal pathologies, such as anal fissures and rectal carcinoma itself, misdiagnosis and delays in care can result. Direct visualization of the rectum via endoscopy, along with biopsy, allows clinicians to make an accurate and timely diagnosis in patients with prostate cancer with rectal involvement, which in turn leads to broader available treatment options.

Hemophagocytic Lymphohistiocytosis Following Skin and Soft Tissue Infection in a Patient With Human Immunodeficiency Virus.

Hemophagocytic lymphohistiocytosis (HLH) is a systemic inflammatory syndrome of inappropriate immune cell activation which can be rapidly fatal if not recognized and treated. Here we discuss a case of a 26-year-old male with HIV on antiretroviral therapy who presented with sepsis secondary to soft tissue infection and ultimately progressed to multi-organ dysfunction despite broad-spectrum antibiotics and an improvement in soft tissue infection. Continued fever and pancytopenia without an explanation found during additional infectious and rheumatologic testing eventually led to bone marrow biopsy and laboratory criteria consistent with HLH. Although pancytopenia is a common finding in patients with HIV, here it marked a more rapidly progressing and fatal disease, HLH. Here we highlight the difficulty in identifying and diagnosing this rare condition, including a discussion of the characteristics, outcomes, underlying etiologies, and treatment of HLH in patients with HIV.

BRCA mutations in pancreatic cancer and progress in their targeting.

Introduction: Genomic instability resulting from DNA damage repair (DDR) deficiencies is a hallmark of cancer and offers treatment opportunities. Homologous recombination DDR defect is a result of multiple critical gene mutations, including BRCA1/2. Targeting DNA DDR defects in pancreatic cancer (PC) is emerging as a potential treatment strategy with current focus on BRCA mutations.Areas covered: Challenges in treating patients with PC are explained. We review DDR defects as a treatment target in PC, specifically, germline BRCA mutation and sensitivity to platinum compounds and exploiting the strategy of synthetic lethality using poly (ADP-ribose) polymerase (PARP) inhibition. Literature review was undertaken through PubMed, Google Scholar, and Clinicaltrials.gov website.Expert opinion: DDR defects are promising targets for novel therapies in PC. Early application of such strategy is in patient subgroup with BRCA germline mutation, which is seen in only 5-7% of the PC population. The oral PARP inhibitor olaparib in the maintenance setting represents the first targeted therapy in metastatic PC based on a phase 3 study. There is a very modest benefit for patients with PC using PARP inhibitors. Future work must improve our understanding of mechanisms of sensitivity and resistance to PARP inhibitors in PC and enhance the molecular selection of patients for such therapy.

Diagnosis and Management of Gastrointestinal Neuroendocrine Tumors: A Comprehensive Literature Review.

Neuroendocrine tumors (NETs) are epithelial neoplasms with predominant neuroendocrine differentiation and the ability to synthesize and secrete variable hormones and monoamines. They are relatively rare, accounting for 2% of all malignancy cases in the United States. The most common system affected by NETs is the gastrointestinal tract. Clinical presentation depends on the organ being involved and the hormone being secreted. It can be variable from asymptomatic incidental findings on imaging to intestinal obstruction, or carcinoid syndrome (CS). Several biochemical testings are developed to help with the diagnosis of NETs including 5-hydroxyindoleacetic acid (5-HIAA) and chromogranin A (CgA). Computerized tomography (CT) scans and magnetic resonance imaging (MRI) are the most commonly used modalities to localize the primary tumor and evaluate for metastasis. However, radionuclide imaging using somatostatin receptor-based imaging techniques has improved accuracy to detect smaller neoplasm. Surgical removal is the mainstay of treatment for locoregional tumors. Several medical managements are available for non-respectable NETs which include SSAs, peptide receptor radionuclide therapy (PRRT), and platinum-based chemotherapy agents.

Ocular Toxoplasmosis Mimicking Lymphoma: Exploring the Correlation and Distinction.

We present a case of a 74-year-old woman with chronic lymphocytic leukemia (CLL) who presented with unilateral blurry vision that had progressively worsened over a few weeks. Ophthalmic examination revealed unilateral anterior chamber, vitreous body inflammation along with retinal infiltration which was initially diagnosed with posterior uveitis. Analysis of vitreous fluid aspiration was negative for bacteria, fungal and viral etiologies. Despite the broad-spectrum intraocular antibiotics, her vision continued to decline, and she later developed retinal detachment. Cytology for lymphoma was negative. However, polymerase chain reaction (PCR) with internal transcribed spacer-specific (ITS) primer set detected Toxoplasma gondii, and the patient was diagnosed with intraocular toxoplasmosis. Treatment with systemic clindamycin, pyrimethamine, leucovorin, prednisone, and topical clindamycin for four weeks successfully prevented further ocular damage.

Meigs' Versus Pseudo-Meigs' Syndrome: A Case of Pleural Effusion, Ascites, and Ovarian Mass.

Meigs' syndrome is classically characterized as the triad of ascites, pleural effusion, and ovarian fibroma. The incidence is not easily determined but has been described in medical literature. We report a case of a patient who presented for shortness of breath and was found to have pleural effusion, ascites, and an ovarian mass. Investigative measures were consistent with Meigs' syndrome; however, definitive diagnosis was not able to be determined as our patient opted for symptomatic treatment rather than pursue surgical options. We discuss the pathophysiology of pleural effusion, ascites, and management of Meigs' and pseudo-Meigs' syndrome. Ultimately, we discuss palliative options for patients who are not ideal candidates for surgery.

Diplopia as the initial symptom of multiple myeloma in a patient with sarcoidosis.

We present the case of a 45-year-old man with a known history of sarcoidosis who presented with double vision and headache. On examination, he was found to have left abducens and hypoglossal nerve palsy. CT and then MRI demonstrated extensive osseous lesions with a large expansile mass involving the clivus bone and sphenoid sinus. Laboratory data were remarkable for normocytic anaemia, low anion gap and elevated total protein which raised the suspicion for multiple myeloma. Subsequent protein electrophoresis and immunofixation illustrated monoclonal spike of IgG lambda present in the gamma zone. This was followed by a bone marrow biopsy that demonstrated plasma cells compromising around 80% of marrow cellularity. Left sphenoidal mass biopsy was consistent with plasmacytoma. Based on these findings, the patient was initially started on palliative radiation to shrink the intracranial tumour and is currently undergoing induction chemotherapy.

The Contribution of NMDA Receptors in Antinociceptive Effect of Pregabalin: Comparison of Two Models of Pain Assessment.

BACKGROUND: Pregabalin has shown remarkable antinociceptive effects in neuropathic pain; however, its efficacy against acute and visceral pain remained controversial. OBJECTIVES: The present study aimed at investigating the involvement of N-methyl-D-aspartate (NMDA) receptors in the antinociceptive effect of pregabalin in both acute and visceral pain using and comparing hot plate test and writhing test in male mice. METHODS: NMDA (15 and 30 mg/kg), as an agonist or MK801 (0.02 and 0.05 mg/kg) as an NMDA receptor (NMDAR) antagonist, were injected intraperitoneally either alone or 15 minutes before a dose of pregabalin that produced almost 30% antinociception (100 mg/kg in hot plate test and 5 mg/kg in writhing tests). Then, the percentage of maximal possible effect (MPE%) at the 30th and 60th minutes in hot plate test and effect percentage (E%) in writhing test were measured and compared as antinociceptive indexes. RESULTS: In hot plate test, pretreatment with MK801 (0.05 mg/kg) significantly increased antinociceptive effect of 100 mg/kg pregabalin, but pretreatment with NMDA did not result in any effect. Pretreatment with MK801 in writhing test significantly increased the antinociceptive effect of 5 mg/kg pregabalin (In contrast to 30 mg/kg NMDA that significantly decreased it.). NMDA induced antinociception reduction or MK801 increased antinociception in writhing test were significantly higher than what was observed in hot plate test. CONCLUSIONS: Our results suggested that pregabalin antinociception in acute and visceral pain is mediated through NMDA receptors. Although this effect depends on the dose of NMDAR ligand, it is more pronounced in the behavioral response in the writhing test.

Comparison of Double and Single Leg Weight-Bearing Radiography in Determining Knee Alignment.

BACKGROUND: Knee malalignment is an important modifiable cause of osteoarthritis (OA). Surgical therapeutic procedures depend on proper knee alignment assessment. The purpose of this study was to compare knee alignment parameters between double and single leg weight-bearing radiographs and to evaluate the reproducibility of inter- and intra-observer measurements. METHODS: One hundred eight patients (59 male and 49 female) with knee deformity visited at Kerman Knee Clinic were selected. Full limb anteroposterior (AP) Radiographs were taken for each participant in double and single leg weight-bearing positions. Hip-Knee-Ankle Angle (HKAA), Medial-Proximal-Tibial Angle (MPTA), Lateral-Distal-Femoral Angle (LDFA) and Joint-Line-Convergence Angle (JLCA) measured. Images stored on PC were examined by three observers to assess inter and intra observer reproducibility. Data analysis was done by SPSS software. RESULTS: The mean age of patients was 48.4 (±6.84) years, mean BMI was 26.55 (±1.94) Kg/m2. The mean HKAA and JLCA were significantly different between double and single leg weight-bearing radiographs. Intraclass correlation coefficient (ICC) test showed high (0.99) inter-reproducibility between three observers in all cases, except one (ICC=0.92). Intra-observer reproducibility indicated a strong correlation between the observer's measurements at different times (ICC > 0.99). CONCLUSION: HKAA and JLCA were affected by the patient's position. Observer and time interval had no effect on either of HKAA, MPTA, LDFA, and JLCA. Also the measurement of knee alignment parameters was not dependent on observer's experience. In conclusion single leg weight-bearing radiography is more representative of knee alignment and is inter and intra-observer reproducible.

The effects of co-administration of pregabalin and vitamin E on neuropathic pain induced by partial sciatic nerve ligation in male rats.

OBJECTIVE: This study was performed to evaluate the effect of pregabalin co-administration with vitamin E in Partial Sciatic Nerve Ligation (PSNL)-induced neuropathic pain in rats. METHODS: Male Wistar rats were randomly allocated as control, sham, and PSNL groups (n = 8). PSNL was induced by tight ligation of the sciatic nerve with a copper wire. On day 14th, the PSNL and sham operated rats received either pregabalin (1, 3, and 30 mg/kg), vitamin E (100 and 200 mg/kg), or their combination intraperitoneally. An antinociceptive effect was evaluated as latency times and Maximum possible Effect Percent (%MPE) using tail-flick test. Locomotor activity was evaluated by open-field test before PSNL surgery and then twice at the 14th days (before and after drug injection). Ligated nerves were removed on the 28th days after surgery for histological examinations. RESULTS: The time course of latency times and %MPE showed significant decrease in PSNL but not in sham and control groups. Pregabalin (3 and 30 mg/kg) and vitamin E (100 and 200 mg/kg) caused significant increases in latency time in PSNL (but not sham) group compared to control group. Vitamin E 200 mg/kg increased significantly %MPE in PSNL group compared to sham group. In addition, the %MPE following combination treatment of pregabalin (30 mg/kg) and vitamin E (100 mg/kg) was significantly higher than both vitamin E and control group. Also combination of pregabalin with 100 mg/kg of vitamin E reversed Wallerian degeneration of sciatic nerve and the inflammatory responses to almost similar to sham group. Pregabalin and vitamin E did not affect locomotor activity. CONCLUSION: Our results showed antinociceptive effects of both vitamin E and pregabalin alone or in combination in PSNL rats and also neuroprotective properties without affecting locomotor activity.