Advancements in Targeted Therapies for the Management of Crohn's Disease: A Comprehensive Review.

Crohn's disease (CD) is a complex clinical condition characterized by persistent gastrointestinal inflammation that leads to episodes of flare-ups and subsequent healing. The treatment options for this disease are heterogeneous as its impact on different patients is also different. This study aims to evaluate the effectiveness of recently approved drugs that specifically target certain pathways within cells that are involved in CD pathogenesis. These medicines include biologics like anti-TNF agents, interleukin inhibitors, and small molecule inhibitors; they work by altering the modulation of immune responses and reducing inflammation. These drugs seem promising in terms of inducing remission in moderate to severe CD among various patient populations. Conversely, it is possible to examine how well these drugs perform using gene expression and molecular markers. By understanding these results along with other ongoing trials, personalized medicine can be used more frequently by doctors who will adopt a strategy for an individual patient, maximizing benefits while minimizing adverse effects. There are still some issues that need to be worked out like the high cost associated with these drugs or immunogenicity risk and infectious complications too. In conclusion, there has been a remarkable improvement in CD management over the past decade with customized drugs leading toward a precision medical era. Further understanding of molecular mechanisms implicated in CD pathogenesis and new therapeutic approaches could potentially improve treatment outcomes among affected individuals. This research is crucial in understanding how CD therapeutics are changing, thus facilitating selection by doctors on the most appropriate methods for individualized patient care.

Bevacizumab Combination Therapy Versus Standard Chemotherapy for Ovarian Cancer in Shorter and Longer Follow-Up Duration: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: This systematic review and meta-analysis aims to evaluate the efficacy and safety of bevacizumab in patients with ovarian cancer over a shorter and longer follow-up period. METHODS: We searched Medline, Cochrane CENTRAL, Scopus, and Google Scholar for all phase 3 randomized controlled trials (RCTs) that administered bevacizumab to women with ovarian cancer. Review Manager 5.4 was used to calculate risk ratios (RR) and hazard ratios (HR) with 95% CIs. We assessed the quality of the included studies using version 2 of the Cochrane Risk of Bias tool (RoB 2). RESULTS: After screening the titles, abstracts, and full texts, we included nine RCTs in our systematic review and meta-analysis. Four RCTs had a low risk of bias, while 5 had some concerns. Bevacizumab was associated with a progression free survival benefit for <36 months (HR: 0.59, 95% CI: 0.45-0.76, P<0.0001, I2=90%) and >36 months (HR: 0.66, 95% CI: 0.55-0.80, P<0.0001, I2=80%), and an overall survival benefit for <36 months (HR: 0.87, 95% CI: 0.78-0.98, P=0.02, I2=0%) but not for >36 months (HR: 0.98, 95% CI: 0.89-1.09, P=0.77, I2=30%). There was no difference in deaths between intervention and control groups <36 months (RR: 0.95, 95% CI: 0.86-1.04, P=0.26, I2=10%) or >36 months (RR: 1.02, 95% CI: 0.97-1.06, P=0.50, I2=0%). Bevacizumab reduced disease progression <36 months (RR: 0.82, 95% CI: 0.72-0.92, P=0.0008, I2=82%) but not at >36 months (RR: 0.83, 95% CI: 0.58-1.19, P=0.30, I2=94%). The adverse events reported with Bevacizumab use included thrombocytopenia, neutropenia, leukocytopenia, anemia, hypertension, bleeding or hemorrhage, and gastrointestinal, cardiac, and dermatological adverse events. CONCLUSION: Bevacizumab may improve progression-free survival within and after 36 months, overall survival within 36 months, and reduce disease progression within 36 months.

Sociodemographic Disparities in the Diagnosis and Prognosis of Patients With Cervical Cancer: An Analysis of the Surveillance, Epidemiology, and End Results Program.

Background While the incidence and mortality rates of cervical cancer are declining due to improved prevention, screening, and treatment, inequitable access to care may contribute to worse patient outcomes. Therefore, we sought to evaluate sociodemographic disparities in the diagnosis and prognosis of patients with cervical cancer. Methodology The Surveillance, Epidemiology, and End Results (SEER) database was queried for adult women diagnosed with cervical cancer from 2010 to 2015. Sociodemographic groups of interest included patient race/ethnicity (non-Hispanic White/Hispanic White/Black/Other), residential setting (rural/urban), and county median household income (<$45,000/$45,000-59,999/$60,000-74,999/≥$75,000). Outcomes of interest included stage at diagnosis, receipt of hysterectomy, and overall survival (OS). Outcomes were evaluated using Pearson's chi-square test, multivariable logistic regression, and multivariable Cox proportional hazards. Results A total of 5,726 patients were identified with an average age of 50.1 years (SD = 14.6). Significant differences in cancer stage at diagnosis were identified based on race/ethnicity (p < 0.001) and household income (p = 0.012). On adjusted analysis, Black patients were found to be significantly less likely to receive a hysterectomy compared to non-Hispanic White patients (odds ratio (OR) = 0.46; 95% confidence interval (CI) = 0.37-0.56). Lower household income was associated with poorer survival for stage I (<$45,000 vs. >$75,000: hazard ratio (HR) = 1.53; 95% interquartile range (IQR) = 1.00-2.33), II ($45,000-59,999 vs. >$75,000: HR = 1.67; 95% IQR = 1.19-2.35), and IV (<$45,000 vs. >$75,000: HR = 1.64; 95% IQR = 1.22-2.29) disease. Black race was associated with poorer OS for stage IV disease (HR = 1.29; 95% IQR = 1.06-1.56). Conclusions This study highlights significant disparities in disease progression at diagnosis and OS for cervical cancer patients based on race/ethnicity and household income. These findings may assist policymakers in developing strategies for mitigating these disparities.

Prostatitis As An Initial Presentation For Granulomatosis With Polyangiitis.

Granulomatosis with polyangiitis (GPA) is an uncommon pauci-immune small-vessel necrotising granulomatous vasculitis mostly seen in age 45-60 years. We present the case of a formerly healthy 44 years old male presenting with dysuria and intermittent urinary retention for 8 months, not responding to empirical antibiotic therapy and TURP. A prostate biopsy showed necrotising granulomatous prostatitis. Urinalysis demonstrated persistent pyuria and haematuria, but cultures showed no growth. Subsequently he complained of fever, cough, dyspnoea and skin ulcers. CT of the chest showed multiple cavitatory lesions and pleural effusion. On work up, c-ANCA was positive and a diagnosis of granulomatosis with polyangiitis was established. This depicts a rarely seen presentation of prostatitis as the initial feature of GPA.

SARS-CoV-2 Antibody Prevalence and Population-Based Death Rates, Greater Omdurman, Sudan.

In a cross-sectional survey in Omdurman, Sudan, during March-April 2021, we estimated that 54.6% of the population had detectable severe acute respiratory syndrome coronavirus 2 antibodies. Overall population death rates among those >50 years of age increased 74% over the first coronavirus disease pandemic year.

Mitochondria in Diabetic Kidney Disease.

Diabetic kidney disease (DKD) is the leading cause of end stage renal disease (ESRD) in the USA. The pathogenesis of DKD is multifactorial and involves activation of multiple signaling pathways with merging outcomes including thickening of the basement membrane, podocyte loss, mesangial expansion, tubular atrophy, and interstitial inflammation and fibrosis. The glomerulo-tubular balance and tubule-glomerular feedback support an increased glomerular filtration and tubular reabsorption, with the latter relying heavily on ATP and increasing the energy demand. There is evidence that alterations in mitochondrial bioenergetics in kidney cells lead to these pathologic changes and contribute to the progression of DKD towards ESRD. This review will focus on the dialogue between alterations in bioenergetics in glomerular and tubular cells and its role in the development of DKD. Alterations in energy substrate selection, electron transport chain, ATP generation, oxidative stress, redox status, protein posttranslational modifications, mitochondrial dynamics, and quality control will be discussed. Understanding the role of bioenergetics in the progression of diabetic DKD may provide novel therapeutic approaches to delay its progression to ESRD.

Patterns of Peripheral Nerve and Tendon Injury in Hand Trauma Patients in a Tertiary Care Hospital of Pakistan.

Introduction Traumatic injury to peripheral nerves is a major medical problem worldwide. Moreover, injury to the hand and wrist can lead to extreme morbidity and disable the injured for life. In this study, we highlight the most commonly damaged nerves and tendons that get ruptured in different types of hand trauma patients. No recent study has been done to document the etiologies and quantify the patterns of nerve and tendon involvement in hand injuries to the best of our knowledge. Methodology This was a cross-sectional study conducted at the largest trauma center in the city and the Plastic and Reconstructive Surgery ward of Civil Hospital, Karachi. A convenient sampling of 200 patients was done with the help of a preformed, well-structured questionnaire. Patients whose hand was injured solely were included in the study and those with the involvement of the whole limb or other parts of the body were excluded. Results We found that most males between the ages of 11 and 20 years presented predominantly with right-hand injury while working with machines. Nerve injury proved to be a rare occurrence. However, combined nerve injury of the ulnar, median, and radial nerve was seen in poly digit trauma. The median nerve was the most commonly damaged nerve in poly digit trauma. Among the tendon injuries, the incidence of combined tendon injury was the greatest. The flexor digitorum superficialis was the most common tendon injured overall. Conclusion This study significantly states that tendons are frequently injured in hand accidents. Plastic surgeons must also be aware of optimal nerve repair and reconstruction techniques to limit the physical disabilities and economic burden arising from nerve injury of the dominant hand.

Endoscopic Findings and Their Association With Gender, Age and Duration of Symptoms in Patients With Dysphagia.

Introduction Dysphagia is highly prevalent in patients with a history of recurrent acid peptic disease. Endoscopy is the mainstay of diagnostic workup of these patients to reach underlying cause and appropriate subsequent treatment. The objective of the study was to determine the frequency of various types of endoscopic findings in patients with dysphagia and the association of these findings with gender, age and duration of symptoms. Methods This cross-sectional study was carried out in the Department of Gastroenterology of a tertiary care hospital in Rawalpindi, Pakistan. A total of 137 patients who presented with a history of dysphagia for at least two weeks were enrolled in the study. Duration of symptoms was noted, and all patients underwent upper gastrointestinal endoscopy to find out the cause of dysphagia. Tissue biopsies were obtained, and further histopathological examination was performed to correlate the findings with symptoms of dysphagia.  Results A total of 137 patients were enrolled for six months. The mean age of the patients was 56.9 ± 17.44 years, and the mean duration of symptoms was 15.96 ± 12.31 weeks. There were 65 (47.4%) males and 72 (52.6%) females in the study. Majority of them, 123 (89.8%), presented with a short duration of symptoms that varied between 2-24 weeks and were mainly middle-aged (31-60 years) and old-aged (61-80 years). The most commonly observed endoscopic findings were esophageal stricture in 25 (18.2%), achalasia cardia in 20 (14.6%), esophageal mass in 12 (8.8%) and reflux esophagitis in 7 (5%) patients. No association was seen between age, gender and duration of symptoms and findings on the endoscopy. Conclusion Dysphagia is associated with many endoscopic findings that are not related to demographic variables and must be evaluated earlier to reduce further morbidity and mortality.

Acid treated biochar enhances cadmium tolerance by restricting its uptake and improving physio-chemical attributes in quinoa (Chenopodium quinoa Willd.).

Heavy metals contamination of soil especially with cadmium (Cd) is a serious environmental concern in the current industrial era. Biochar serves as an excellent ameliorating agent depending upon its properties and application rates. In the pot scale study, effect of acid treated (AWSB) and untreated wheat straw biochar (WSB) was studied on physiology, grain yield, Cd accumulation, and tolerance of quinoa with possible health risks. Different levels of Cd (0, 25, 50 and 75 mg kg-1), AWSB and WSB (1% and 2% (w/w)) were applied in soil. Accumulation of Cd in control plant tissues led to oxidative stress which was shown in terms of increased lipid peroxidation. While biochar application relieved the oxidative damage as confirmed by the low production of H2O2 and TBARS contents. Application of AWSB improved plant growth, pigment contents and gas exchange attributes by limiting the accumulation of Cd in root, shoot and grain of quinoa. Results revealed a significant improvement in the activity of superoxide (SOD), catalase (CAT), ascorbate peroxidase (APX) and peroxidase (POD) with biochar at elevated levels of Cd in soil. Target Hazard Quotient (THQ) remained < 1 in the quinoa grains with WSB and AWSB under Cd stress. These results revealed that AWSB most effectively alleviated Cd toxicity in quinoa thereby decreasing Cd accumulation and regulation of Cd induced oxidative stress triggered by the antioxidant enzymatic system.

Primary Acquired Toxoplasma Retinochoroiditis: Choroidal Neovascular Membrane as an Early Complication.

Ocular toxoplasmosis occurs subsequently after systemic infection with the protozoan parasite, Toxoplasma gondii (T. gondii). The parasite has a high affinity for retinal microvascular endothelium with the retina being the primary site of infection in the eye. Choroidal neovascular membrane (CNVM) is a late complication of ocular toxoplasmosis, mostly occurring in healed, inactive lesions and may be a cause of sudden loss of vision, especially in young patients. However, we report a case of a 22-year-old female who presented to our clinic with CNVM as an early complication. She complained of metamorphopsia and diminished vision in her right eye. Ocular examination, serological investigation and fundoscopy, fundus fluorescein angiography (FFA), axial optical coherence tomography (OCT), and optical coherence tomography angiography (OCTA) were carried out and a diagnosis of primary acquired Toxoplasma retinochoroiditis with active CNVM was made. Treatment was commenced with sulfamethoxazole and trimethoprim. Oral prednisolone and intravitreal injection of the anti-vascular endothelial growth factor (anti-VEGF), bevacizumab, were also given. This report describes the rare presentation of ocular toxoplasmosis as a primary lesion in which adjacent pre-existing fundal scarring was absent. The lesion had an acquired etiology in an immunocompetent patient and was complicated early by CNVM.

Transient receptor potential vanilloid 4 channels are important regulators of parenchymal arteriole dilation and cognitive function.

OBJECTIVE: Hypertension-associated PA dysfunction reduces cerebral perfusion and impairs cognition. This is associated with impaired TRPV4-mediated PA dilation; therefore, we tested the hypothesis that TRPV4 channels are important regulators of cerebral perfusion, PA structure and dilation, and cognition. METHODS: Ten- to twelve-month-old male TRPV4 knockout (WKY-Trpv4em4Mcwi ) and age-matched control WKY rats were studied. Cerebral perfusion was measured by MRI with arterial spin labeling. PA structure and function were assessed using pressure myography and cognitive function using the novel object recognition test. RESULTS: Cerebral perfusion was reduced in the WKY-Trpv4em4Mcwi rats. This was not a result of PA remodeling because TRPV4 deletion did not change PA structure. TRPV4 deletion did not change PA myogenic tone development, but PAs from the WKY-Trpv4em4Mcwi rats had severely blunted endothelium-dependent dilation. The WKY-Trpv4em4Mcwi rats had impaired cognitive function and exhibited depressive-like behavior. The WKY-Trpv4em4Mcwi rats also had increased microglia activation, and increased mRNA expression of GFAP and tumor necrosis factor alpha suggesting increased inflammation. CONCLUSION: Our data indicate that TRPV4 channels play a critical role in cerebral perfusion, PA dilation, cognition, and inflammation. Impaired TRPV4 function in diseases such as hypertension may increase the risk of the development of vascular dementia.

Neuro-imaging evaluation after the first afebrile seizure in children: A retrospective observational study.

PURPOSE: To evaluate the role of neuro-imaging in children presenting with the first afebrile seizure and determine factors that influence the outcome of imaging in a large paediatric emergency centre. METHOD: This is a retrospective review of the medical records of all patients presenting with the first non-febrile seizure to a large paediatric emergency centre in the state of Qatar. Seizure classification followed the current ILAE classification system. Imaging was undertaken in our tertiary hospital and all images were reviewed by experienced neuro-radiologists. Student t test was used for statistical analysis. RESULTS: Ninety-six children underwent neuro-imaging following the first afebrile seizure. Of them, thirty-two patients (33%) were reported to have abnormalities. Children below the age of two demonstrated a significantly higher percentage of abnormal imaging (59%); (p=0.002). Children presenting with prolonged seizures showed a high percentage of imaging abnormalities (58%); (p=0.003). Children with focal seizures demonstrated a higher percentage of imaging abnormality compared to those presenting with generalized seizures (35% vs 31%). This difference did not reach statistical significance. CONCLUSION: Children below the age of two demonstrated significantly higher percentages of abnormal imaging (59%), as did children presenting with status epilepticus (58%). Neuro-imaging should be considered in infants and those with focal or prolonged seizures. Neuro-imaging informed decision making in 6-8% of children.

Primary sigmoid adenocarcinoma metastasis to the breast in a 28-year-old female: a case study and a review of literature.

Metastasis to the breast from colorectal carcinoma is rare, only a few cases have been reported in the literature, and no cases have been reported in a young, 28-year-old patient. This report confirms the occurrence of the disease in a younger age group. The patient was referred to the Breast Clinic with a history of a gradually increasing lump in her right breast for two weeks' duration. On clinical examination, a 2-cm firm lump was noted in the upper inner quadrant of the right breast, which was clinically benign; however, histological examination of the breast core biopsy together with immunohistochemistry confirmed metastatic colorectal adenocarcinoma. The primary colorectal carcinoma was later confirmed to be a stage pT4N2M1 tumor, and the Duke stage was C1. Histology with immunohistochemistry is very important in the diagnosis of cases of this nature, but the clinical correlation should be taken into consideration at multidisciplinary team meetings to decide the final management of the patient.

Intracystic papillary carcinoma of breast: report of three cases and review of the literature.

Intracystic papillary carcinoma (IPC) of the breast is a rare malignant tumour, found mainly but not exclusively in elderly women. IPC may be asymptomatic or presents with a palpable mass or blood-stained nipple discharge. The tumour is encysted within a dilated duct with arborisation of the fibrovascular stroma and contains nodules of papillary carcinoma surrounded by a thick fibrous capsule. Frequently excisional biopsy is required for diagnosis. The mainstay of treatment is breast-conserving surgery or mastectomy. Sentinel node biopsy could be considered in invasive cases. Adjuvant radiotherapy (XRT) and/or endocrine therapy is considered in appropriate cases. Prognosis is excellent. We report three such cases of IPC, in elderly women, which were successfully treated.