Chronic Kidney Disease of Unknown Origin: A Mysterious Epidemic.

Amongst the many threats to health in our world, the most challenging ones are the ones with unknown causes. There is a mysterious epidemic of kidney disease called chronic kidney disease of unknown etiology (CKDu) that is occurring in many parts of the world. Unrelated to known risk factors such as diabetes and hypertension, CKDu mostly affects the young and middle-aged, with slight preponderance in males. It mostly occurs in people living in rural areas, especially working in agricultural jobs. Worldwide, the number of people with chronic kidney disease, and those who need dialysis and renal replacement, is increasing every year as compared to other chronic conditions like diabetes and AIDS. It's not just alarming but a great challenge to healthcare systems across the world, especially in resource-poor countries. CKDu has become a silent killer for most patients. The occurrence of end-stage renal disease (ESRD) in CKDu can be catastrophic for individuals, especially in countries with limited medical facilities, causing a significant socio-economic burden. Even within these economically developing nations, people affected by CKDu usually are from the most vulnerable and underserved populations. As a definitive etiology has not been postulated for CKDu to date, this comprehensive review was undertaken to throw light on the poorly understood epidemiologic risk factors and the course of the disease.

Virtual Reality Intervention to Help Improve Motor Function in Patients Undergoing Rehabilitation for Cerebral Palsy, Parkinson's Disease, or Stroke: A Systematic Review of Randomized Controlled Trials.

There are many successful interventions in medicine, especially in neurology and rehabilitation. The neurosciences represent an area of medicine with tremendous recent research innovations, one of which is virtual reality. This paper aims to discover the powerful relationship between virtual reality and rehabilitation. We assessed the effectiveness of virtual reality-based rehabilitation compared to conventional rehabilitation on motor function recovery of three patient groups: patients with a diagnosis of cerebral palsy, Parkinson's disease, or stroke. We conducted a systematic review using PubMed and included only articles that were randomized controlled trials that were published in the last five years. We used a general search in combination with a more focused Medical Subject Headings (MeSH) search. After thorough assessment and risk of bias evaluation using the Cochrane risk of bias tool, we included thirteen studies in this review. The majority of the clinical trials showed a statistically significant effect for improved motor function. More specifically, improvements in upper extremity motor function, gait, and balance in patients diagnosed with stroke were seen. Similarly, when evaluating patients with Parkinson's disease, improved gait and posture were also seen. When it came to cerebral palsy, however, there were no significant differences between the experimental group and the control. The level of improvement in motor function with a virtual reality intervention was striking, particularly since a few studies demonstrated sustained motor improvement a few months post-trial as well. Virtual reality-based rehabilitation has promising results for adult patients diagnosed with stroke or Parkinson's disease. For pediatric patients, on the other hand, a larger number of clinical trials would still need to be conducted to validate if virtual reality interventions have the capability of providing improved motor function recovery.

Surgical and Patient Outcomes of Robotic Versus Conventional Laparoscopic Hysterectomy: A Systematic Review.

Hysterectomy is a commonly performed gynecologic surgery that can be associated with significant morbidity and mortality. However, the evolution of the surgical approach, from open to minimally invasive gynecologic surgery (MIGS), has substantially improved patient outcomes by reducing perioperative complications, pain, and length of hospitalization. The evident advantages and the approval of the da Vinci Surgical System by the Food and Drug Administration led to the exponential rise in the use of MIGS. In particular, robotic hysterectomy (RH) witnessed unparalleled popularity compared to other MIGS despite the lack of strong evidence demonstrating its superiority. Therefore, we conducted a systematic review of the literature to evaluate and compare various patient and surgical outcomes of RH with conventional laparoscopic hysterectomy (CLH), including operating time, estimated blood loss, length of hospitalization, overall complications, survival, and cost. Overall, the outcomes were comparable between RH and CLH except concerning cost. RH is significantly more expensive than CLH due to the higher costs of robotic equipment, including disposable instruments, equipment maintenance, and sterilization. Although RH demonstrated comparable outcomes and higher costs, its technical advantages such as improved ergonomics, three-dimensional view, a wider range of wristed mobility, mechanical lifting of robot's hand, and greater stability might benefit patient subsets (e.g., obesity, large uterine weights >750 g). Therefore, large and multicentered randomized control trials are imperative to determine the most effective surgical approach between RH and other MIGS for different patient subsets.

Correlation Between the Gut Microbiome and Immunotherapy Response in Inflammatory Bowel Disease: A Systematic Review of the Literature.

Inflammatory bowel disease (IBD) is an autoimmune disease associated with dysbiosis within the gastrointestinal tract. Characteristic taxonomic shifts of microbial populations are observed in disease progression and remission; however, despite similarities, there are many differences among individuals presenting with IBD including IBD subset, clinical course, and response to therapy. Much is still unknown about how these taxonomic shifts interact with immunotherapy and how genetic variants contribute. In this systematic review, we aimed to compile information on the interactions of the gut microbiome with immunotherapy in the course of disease and treatment of IBD patients. This systematic review was conducted as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and the PubMed database was methodically screened for literature search including keywords and Medical Subject Headings (MeSH) terms for relevant articles. The quality appraisal was completed using the Cochrane Tool, Newcastle-Ottawa checklist, and the Scale for the Assessment of Narrative Review Articles (SANRA) checklist, as appropriate, and 11 relevant articles were included in this systematic review. Our review concludes that although there are characteristic taxonomic shifts between diseased and healthy patients, genetic variants are an important consideration in the predictive quality of disease and treatment decisions. The comparison between interactions of microbial populations and treatment in addition to the role of genetic variants may provide insight into treatment non-responders. Due to our limitations in current knowledge including the complexity of the microcosm, ethnic genetic variations among human populations, and our focus on relevant articles published in English over the past six years, we may have missed relevant studies. Future studies should focus on the comparison between Western and other cultural populations as well as further implementation of Genome-Wide Association Studies (GWAS) in clinical predictability.

Do COVID-19 and SARS Gene Complexities and Variations Help Overcome the Knowledge Gap?

A whole new pathogen, to which humans have virtually no pre-existing immunity, has caused fear all over the world. Severe acute respiratory syndrome coronavirus (SARS CoV-2) is one of the types of human novel-coronavirus of the family coronavirus. The nature of transmission of the virus makes it one of the most infectious pathogenic diseases that has ever existed. Though the human coronaviruses have existed since the discovery of the human coronavirus 229E (HCoV-229E) and human coronavirus OC43 (HCoV-OC43) in 1960, it has been a challenge to develop an effective cure as well as vaccine for the diseases associated with coronaviruses. Commonly, human coronaviruses cause illnesses such as intestinal and respiratory tract illnesses. Nevertheless, the symptoms reflected after infection from the coronaviruses take some time before being identified. Thus, viruses can replicate and cause more harm to the human body before being detected. Moreover, research continues to explain why some gene variations in some individuals increase the risk of some infectious diseases, while others are not affected. Looking at gene variations in people infected with Coronavirus Disease 2019 (COVID-19) and studying how genes influence people's response to infection will help to develop a vaccine that will help strengthen the immune system. Knowing how the human genes respond to the virus COVID-19 will help to cure people more effectively.

HIV, Antiretroviral Therapy and Metabolic Alterations: A Review.

The introduction of antiretroviral therapy (ART) has caused some metabolic problems to people who suffer from HIV. ART probably is not the sole reason for these metabolic disorders. Most likely, HIV itself affects the metabolism as well. We conducted research to find the prevalence of the different types of metabolic disorders among HIV(+) patients. Female gender, high BMI, and older age are among the risk factors for the occurrence of metabolic disorders. Regarding dyslipidemia, hypertriglyceridemia and low high-density lipoproteins (HDLs) are the most common types of dyslipidemia in the studies we included. Protease inhibitors (PIs) are widely known as the most common class of antiretroviral drugs that cause metabolic disorders, and some studies in our review also demonstrated this knowledge. In our review, we concluded that HIV and ART concurrently alter the metabolism, but further research is required about this substantial topic.

Immune Checkpoint Inhibitors in Lung Cancer: Role of Biomarkers and Combination Therapies.

Lung cancer is the leading cause of cancer-related death worldwide, with a poor prognosis. Despite aggressive treatment, progression-free survival (PFS) and overall survival are limited. Recently, various kinds of immune checkpoint inhibitors (ICIs) have emerged for several cancers, targeting PD1, PDL1, and CTLA-4. ICIs have made a significant breakthrough in cancer and revolutionized the management of cancer including lung cancer. However, there are a lot of controversies regarding which group of patients is most suitable to be treated with ICIs in terms of monotherapy, combination, and predictive biomarkers. We reviewed various kinds of studies, such as meta-analysis, randomized control trials, multi-center cohort studies, and case-control studies from PubMed written in English from the last five years. ICIs have significant benefits in the overall survival compared with traditional chemotherapy. Patients with a higher level of PDL1 expression and high tumor mutational burden (TMB) have a higher response rate, and those with EGFR-/ALK- were better than those with EGFR+/ALK+. The patient who responded to immunotherapy completely can still maintain the efficacy after two years of treatment. Neoadjuvant immunotherapy in patients with resectable non-small cell lung cancer resulted in a 45% major pathology response (MPR) and 40% downstaging. Combined therapy (ICIs + chemotherapy) was better than chemotherapy alone, irrespective of PD-L1 expression. A combination of ICIs such as CTLA-4 and PD-1/PD-L1 improved PFS as well. Radiochemotherapy ahead of ICIs is promising as well. However, ICIs combined with EGFR/ALK-TKI (tyrosine kinase inhibitor) are not suggested for the time being. PDL1 expression, TMB, and EGFR/ALK mutations are promising predictive biomarkers. Gut microbiota, galectin-3, and intensity of CD8 cell infiltration are other potential predictive biomarkers. These are very important in the future management of lung cancers as they can prevent unnecessary toxicities and cost of treatment.

Is routine ureteral stenting necessary after uncomplicated ureteroscopic lithotripsy for lower ureteral stones larger than 1 cm?

We evaluated the need for routine ureteral stenting after uncomplicated ureteroscopic lithotripsy (URSL) without dilation for lower ureteral stones larger than 1 cm. A total of 43 patients underwent URSL for lower ureteral stones larger than 10 mm. They were randomized into a stented (21) or an unstented (22) group. URSL was performed by using a semirigid ureteroscope and pneumatic lithotripter without ureteral dilation. Additional forceps application (AFA) was used to remove fragments > or =4 mm. Patients in each group were assessed for stone-free rate, stone size, operative time, AFA, hospitalization time, postoperative pain, irritative voiding symptoms, hematuria, re-hospitalization and stricture formation. The stone-free rate was 100% in each group. There were no statistical differences in the two groups regarding stone size, operative time, AFA, postoperative pain, hematuria and hospitalization time. However, irritative voiding symptoms of the stented group were significantly higher than those in the unstented group (P < 0.05). One patient (4.5%) in the unstented group required re-hospitalization for severe flank pain with fever (>38 degrees C) compared to one patient (4.7%) in the stented group for proximal stent migration (P > 0.05). Stricture formation was not demonstrated in either group at 3 months follow-up excretory urography (EXU). Our results demonstrate that ureteral stenting after uncomplicated URSL without dilation for lower ureteral stones larger than 1 cm does not appear to be necessary if AFA is used to remove fragments > or =4 mm, thereby reducing morbidity of patients and risk of re-hospitalization.

Management of bladder stones with pneumatic lithotripsy using a ureteroscope in children.

PURPOSE: To evaluate the effectiveness and safety of pneumatic lithotripsy by using a ureteroscope to treat bladder stones in children. PATIENTS AND METHODS: Twenty-seven boys presenting with bladder stones underwent transurethral cystolithotripsy. The indication for transurethral cystolithotripsy was stone size

Prospective evaluation of the alterations in the morphology and vascular resistance of the renal parenchyma with color Doppler ultrasonography after percutaneous nephrolithotomy.

PURPOSE: To evaluate the kidneys with color Doppler ultrasonography (CDUS) to determine whether percutaneous nephrolithotomy (PNL) causes renal parenchymal damage. PATIENTS AND METHODS: In 24 patients who underwent unilateral PNL with single renal pole access, cortical thickness, echogenicity, and resistive index (RI) were measured in each pole of the operated and contralateral kidney separately before and at postoperative day (POD) 1, and at 3, 6, and 12 months after PNL. RESULTS: The mean age of the patients was 36.67 +/- 14.68 years. The serum creatinine level increased significantly immediately after PNL but diminished to the preoperative level at POD 1. Changes in serum blood urea nitrogen and electrolyte levels were insignificant. Mean cortical thickness increased significantly in the access pole and contralateral kidney and insignificantly in the nonaffected pole. No statistically significant change was recorded in parenchymal echogenicitiy. Statistically significant differences in cortical thickness between the access pole and the contralateral kidney and between the nonaffected pole and the contralateral kidney disappeared 3 months later. Differences in mean cortical thickness between the access pole and the nonaffected pole were insignificant at all examination periods. Echogenicity was greater in the access pole and the nonaffected pole than in the contralateral kidney only at POD 1. No significant difference was noted in the echogenicity between the access pole and the nonaffected pole. Mean RIs were lower than the universally accepted pathologic RI level (0.70) at all periods. There was no statistically significant difference between the mean RI values of the access pole, nonaffected pole, and contralateral kidney. CONCLUSION: PNL does not cause obvious renal dysfunction and significant parenchymal scarring, which is indicated by the decrease in cortical thickness and increases in cortical echogenicity and intrarenal RI.

Can the levels of nitric oxide in the urine, serum and tumor tissue be putative markers for bladder cancer?

AIM: To determine nitric oxide (NO) levels in serum, urine, tumor tissue and non-malignant adjacent tissue in bladder cancer patients compared with those in patients with a non-neoplastic genitourinary disease and to evaluate postoperative serum and urine NO change. METHODS: Samples was collected in 20 cancer and 41 control patients. Griess reagent was used for NO measurements. RESULTS: Mean age in the cancer and control groups was 64.2 +/- 9.9 and 63.7 +/- 8.9 years, respectively. Preoperatively, urinary infection incidence was not statistically different between groups. There were no significant differences in serum, urine and tissue NO levels in patients with and without infection in both groups. Hematuria was found to not affect urine NO level in the cancer group. Urine NO level was significantly higher than in controls preoperatively, decreased significantly following operation and remained stable after the third month. High serum NO values decreased at the early postoperative period; however, they re-increased in the long-term. No significant differences were observed in the third month in serum and urine NO levels between the patients with (no. 6) and without (no. 14) residual or relapsing tumor. No statistical difference was observed between NO levels in non-malignant adjacent and control tissues. However, tumor tissue NO level was significantly higher than those in the other two. There were no statistical differences in the first and third month serum and urine NO levels between patients who underwent bacillus Calmette-Guérin instillation therapy postoperatively and the patients who took chemotherapy or no further treatment. CONCLUSIONS: Both local and generalized host defense mechanisms seem to function in bladder cancer patients. Although further evaluation with a longer observation period and larger numbers of patients is necessary, results suggest that serum and urine NO levels are not putative and useful markers for bladder cancer.

Increased prevalence of varicocele in patients with coronary artery ectasia.

BACKGROUND: Coronary artery ectasia (CAE) is defined as localized or diffuse non-obstructive lesions of the epicardial coronary arteries with a luminal dilation exceeding the 1.5-fold of normal adjacent segment or vessel diameter. Varicocele is the dilatation of the pampiniform plexus. Recently increased prevalence of peripheral varicose veins has been shown in patients with CAE. In this study we aimed to assess the prevalence of varicocele, which is dilatation of another venous system, in patients with CAE. MATERIALS AND METHODS: Thirty-five male consecutive patients with coronary artery ectasia in combination with or without coronary artery disease (CAD) and 63 male, age-matched patients with coronary artery disease were included in the study. All patients were evaluated for the presence of varicocele. RESULTS: Twenty-one patients with CAE were found to have varicocele (62% of group I patients). In patients with CAD, 24 patients (38%) were found to have varicocele. The difference between the two groups in respect to presence of varicocele was statistically significant (P=0.02; odds ratio=1.57; 95% confidence interval 1.05- 2.3). CONCLUSION: We have shown that patients with coronary artery ectasia have an increased prevalence of varicocele compared to those with coronary artery disease. The mechanism underlying coronary artery ectasia might further increase the prevalence of varicocele in susceptible patients.

Case report of a giant renal oncocytoma.

This report represents the third largest renal oncocytoma in English literature. The tumor was considered as a renal cell carcinoma preoperatively based on the physical examination and radiographic findings.