Volume 34, Issue 6

Introduction Phosphodiesterase 5 inhibitors (PDE5-is) are used worldwide as first line therapy for erectile dysfunction (ED). Current literature reported data on the warning association between PDE5-is use and the development of cutaneous melanoma. However, these data are contrasting, thus we aim to summarise evidence regarding this association. Content A systematic review of all published articles related to the effects of PDE5-is in the development of cutaneous melanoma was performed. PubMed, EMBASE, and Cochrane library were queried for all the published studies indexed up to the 26th of May 2023. A combination of keywords related to PDE5-is and melanoma were used. Only original studies based on human subjects in the English language were included in the analysis. Summary and Outlook Of 505 articles identified, only eight original articles were considered for further analysis. Overall, five of the selected articles including 657,984 subjects agrees on an increased risk of developing melanoma in PDE5-is users. On the other hand, three original articles based on data regarding 360,915 subjects, disagree with the previous statement declaring any association between PDE5-i use and melanoma. Current literature still reports contrasting data regarding the association between PDE5-is assumption and increased risk of melanoma, but a possible association is described, bringing attention to higher risk melanoma category of patients. More clinical studies are needed to clarify the impact of PDE5-is in the development and progression of melanoma.

Stem cells have demonstrated significant potential for tissue repair and regeneration, making them a promising therapeutic avenue in sports medicine. This review aims to provide a comprehensive overview of the current state of research on the application of stem cells in sports medicine. We will discuss the types of stem cells used, their mechanisms of action, and the clinical outcomes of stem cell therapy in different sports-related injuries. Furthermore, we will delve into the challenges and ethical considerations associated with stem cell therapy, as well as future directions and potential applications of stem cells in sports medicine.

Objectives Acute pancreatitis (AP) is an inflammatory disease of the pancreas with high morbidity and mortality. This study investigates the effect of Moring oleifera (MO) on L-arginine-induced AP in Wistar rats. Methods Male Wistar rats were randomly divided into seven groups. Control, AP, Magnesium groups, all fed with standard rat diet, MO leaf groups (5% MLF and 15% MLF), and MO seed groups (5% MSD and 15% MSD) were fed with five or 15% MO leaf or seed supplemented diet for four weeks prior to induction of AP. AP was induced by administration of double doses of L-arginine (320 mg/100 g i.p.) at 1 h interval. All animals were sacrificed 72 h thereafter. Results Weekly mean feed consumption and body weight were significantly higher in MO groups compared to the control. Amylase level, MDA, MPO, and NO were significantly higher in the AP group than in the control but decreased in Mg and MO groups. While CAT, SOD, GSH, and SH-group were significantly depleted in AP groups, which was attenuated in MO groups. Rats in AP groups showed severe inflammation, necrosis, and edema. These effects were significantly improved in MO groups resulting in lower histological scores compared to the AP group. Conclusions Pretreatment with MO could attenuate AP via its antioxidant and anti-inflammatory action.

Objectives Systemic absorption of the irrigating fluid used to flush the operating site is a potentially serious complication in several types of endoscopic operations. To increase safety, many surgeons have changed from a monopolar to a bipolar resection technique because 0.9% saline can then be used instead of electrolyte-free fluid for irrigation. The present study examines whether the tendency for excessive plasma volume expansion is greater with saline than with electrolyte-free fluid. Methods Pooled data were analyzed from four studies in which a mean of 1.25 L of either 0.9% saline or an electrolyte-free irrigating fluid containing glycine, mannitol, and sorbitol was given by intravenous infusion on 80 occasions to male volunteers and patients scheduled for transurethral prostatic surgery. The distribution of the infused fluid was analyzed with a population volume kinetic model based on frequently measured hemodilution and the urinary excretion. Results Electrolyte-free fluid distributed almost twice as fast and was excreted four times faster than 0.9% saline. The distribution half-life was 6.5 and 10.6 min for the electrolyte-free fluid and saline, respectively, and the elimination half-lives (by urinary excretion) from the plasma volume were 21 and 87 min. Simulation showed that the plasma volume expansion was twice as great from 0.9% saline than from electrolyte-free fluid. Conclusions Isotonic (0.9%) saline expands the plasma volume by twice as much as occurs with electrolyte-free irrigating fluids. This difference might explain why signs of cardiovascular overload are the most commonly observed adverse effects when saline is absorbed during endoscopic surgery.

Objectives Cardiovascular diseases, especially atherosclerosis, are the leading cause of human mortality in Indonesia. Ipomoea batatas (L.) is a food plant used in Indonesian traditional medicine to treat cardiovascular diseases and related conditions. We assessed the anti-atherosclerotic activity of the aqueous extract of I. batatas leaves in a rat model of high-fat diet-induced atherosclerosis and its mechanism. Methods The presence of amino acid content in the I. batatas L. purple variant was determined by liquid chromatography high-resolution mass spectrometry (LC-HRMS). Thirty male Wistar rats were divided into five groups (n=6/group), i.e., standard diet group (SD), high-fat diet group (HF), and HF plus I. batatas L. extracts orally (625; 1,250; or 2,500 mg/kg) groups. The numbers of macrophages and aortic wall thickness were analyzed histologically. Immunohistochemical analyses were performed to assess foam cells-oxidized low-density lipoprotein (oxLDL), endothelial nitric oxide synthase (eNOS), and vascular endothelial growth factor (VEGF) expression in the aorta. Results LC-HRMS analysis showed nine amino acid content were identified from I. batatas L. In vivo study revealed that oral administration of I. batatas L. leaf extract alleviated foam cells-oxLDL formation and aortic wall thickness caused by high-fat diet atherosclerosis rats. Further, I. batatas L. leaf extract promoted the number of macrophages and modulated VEGF and eNOS expression in the aorta. Conclusions I. batatas L. leaf extract shows a positive anti-atherosclerosis effect. Furthermore, the mechanism may promote the macrophages, eNOS, VEGF expressions, and inhibition of foam cells-oxLDL formation and aortic wall thickness with the best dosage at 2,500 mg/kg. This could represent a novel approach to prevent cardiovascular diseases.

Objectives Diabetic peripheral neuropathy (DPN) is a common diabetes complication. The prevalence of neuropathy is 55% for type 1 and 66% for type 2 diabetes. In Unani medicine neuropathy is known as Khidr (numbness). It is treated with drugs possessing hypoglycemic and analgesic properties, etc . Habb-e-Asab , a polyherbal Unani formulation used for the treatment of Waja-ul-Asab (neuralgia) is routinely used for its indications in neurological pain in Unani medicine. The aim of this study to investigate the efficacy of Habb-e-Asab in diabetic peripheral neuropathy. Methods Thirty patients with DPN were randomly assigned to test (n=20) and control (n=10) groups in a randomized single-blind placebo control study. For 45 days, the test group was given 250 mg Habb-e-Asab twice a day and the control group 250 mg placebo twice a day. The subjective parameters Pain in feet, burning in feet, and tingling in feet was assessed by the arbitrary scale and VAS fortnightly and objective parameters MNSI, and VPT was assessed in pre–post-treatment. Results The research drug revealed highly statistically significant with p<0.001 on VAS score and MNSI whereas VPT is significant with p<0.01 on few points. But control group exhibits no significant effect in any of the parameters. No adverse effects had been reported in either group. Conclusions Our finding indicated that the Habb-e-Asab for 45 days improved and reduced the severity of DPN in a patient with diabetes (CTRI/2018/02/011725).

Objectives Ischemia–reperfusion (I–R) injury is the most common cause of acute kidney injury (AKI). Experimental studies have shown that indoleamine 2,3-dioxygenase 1 (IDO) and the purinergic receptor P2X7 contribute to kidney I–R injury. We evaluated whether there is an interplay between IDO and P2X7 in the pathogenesis of I–R injury. Methods Primary renal proximal tubular epithelial cells (RPTECs) were subjected to anoxia or reoxygenation with or without specific inhibitors. Cell imaging, colorimetric assays, and Western blotting were used. Results Cell imaging revealed that inhibition of IDO, or all the purinergic receptors with an ATPase, or specific inhibition of P2X7 rescued the cells from anoxia or reoxygenation-induced cell death. This was confirmed with LDH release assay, which also detected the ferroptotic nature of cell death due to reoxygenation. On the contrary, activated cleaved caspase 3 increased during anoxia, showing that apoptosis prevails. All the aforementioned treatments prevented caspase increase. Both anoxia and reoxygenation increased extracellular ATP, IDO, and P2X7 expression. IDO remained unaffected by the above-mentioned treatments. On the contrary, treatment with apyrase or inhibition of P2X7decreased extracellular ATP and P2X7 expression, which are also decreased by inhibition of IDO. The first indicates a positive feedback loop regarding P2X7 activation, expression and function, while the latter implies that IDO controls P2X7 expression. Conclusions In RPRECs subjected to anoxia or reoxygenation, IDO is upregulated, increasing P2X7 and contributing to anoxia or reoxygenation-induced cell death. Clarifying the molecular mechanisms implicated in kidney I–R injury is of particular interest since it may lead to new therapeutic strategies against AKI.

Objectives Breakfast replenishes glucose homeostasis and provides other micro-nutrients for the normal functioning of the body after a long night at night. Habitually skipping breakfast leads not only to metabolic disturbances but also to neurocognitive impairment. Hence, the current study was carried out to study the effect of skipping breakfast on neurocognitive functions. Methods A 9-item breakfast questionnaire was distributed online to students for identifying habitual breakfast skippers from non-skippers based on inclusion criteria. Random blood glucose was noted and visual and auditory reaction time, critical flicker fusion frequency, and Stroop test were assessed in both groups to assess cognition. Results Forty one habitual breakfast skippers who met the inclusion criteria showed increased visual reaction time, and auditory reaction time indicating cognitive impairment. A significant reduction in the Stroop test was observed among the non-skipper group when compared to the skipper group. Conclusions This study suggests that skipping breakfast diminishes neurocognitive functions like problem-solving, planning, judgment, information retention, and reasoning.

Objectives One of the major risk factors for cardiovascular disease is obesity, particularly abdominal and visceral obesity. Another concern for it is inflammation. Both risk factors are interrelated as obesity is a state of subacute low-grade systemic inflammation. As neck circumference and waist-hip ratio are potential indicators of obesity, we wanted to compare the level of total leukocyte count in subjects with normal and high neck circumference and waist-hip ratio. We also wanted to observe whether there is any correlation between neck circumference and waist-hip ratio with total leukocyte count. Methods We selected 62 subjects (30 males, and 32 females) for the study. Both males and females were categorized into groups of normal and high neck circumference and waist-hip ratios. The total leukocyte count was compared among the groups and we correlated neck circumference and waist-hip ratios with total leukocyte count. Statistical analysis was done with SPSS version 23.0. Results We observed a statistically significant higher value of total leukocyte count in males with a high waist-hip ratio. But there was not a significant increase in TLC in males with high neck circumference. In females, the values were insignificant. On Pearson correlation, there was a negative correlation between neck circumference, waist-hip ratio, and total leukocyte count in both genders which is not significant. Conclusions These findings suggest that waist-hip ratio rather than neck circumference might be a proxy measure of a marker of inflammation in males.

Objectives This study aimed to assess the efficacy of the 3-day food records in monitoring and enhancing dietary habits among patients with type 2 diabetes mellitus. Methods A total of 49 patients with type 2 diabetes mellitus were enrolled, with 38 completing the study. Participants were instructed to record their food intake over 3 consecutive days every 2 months. Key anthropometric and glycometabolic parameters, including body weight, abdominal circumference, glycated hemoglobin, and fasting blood sugar, were evaluated at baseline and after 6 months. Results The introduction of the 3-day food records led to significant improvements in body weight, abdominal circumference, glycated hemoglobin, and fasting blood sugar. Additionally, there was a notable increase in the percentage of patients adhering to the LARN nutritional recommendations, especially concerning the intake of carbohydrates, simple sugars, proteins, fiber, and water. However, adherence to lipid and saturated fat recommendations remained a challenge. Conclusions The 3-day food records emerges as a valuable tool in the dietary management of patients with type 2 diabetes mellitus. By facilitating real-time monitoring and feedback, it holds promise in enhancing patient adherence to nutritional guidelines, thereby improving key health outcomes.

Objectives Cardiovascular disease (CVD) remains the primary cause of mortality in individuals with type 2 diabetes mellitus. Digital health has quickly emerged as a technology with the ability to bridge the gap in cardiovascular disease self-management and revolutionize the way healthcare has traditionally been delivered. However, there is little data on the application of mobile technologies for cardiovascular risk reduction among diabetic patients. The current study has been constructed with this in mind. Methods A framework for the development of a healthy heart mobile application for CVD risk stratification and risk management among Type 2 diabetes mellitus patients was finalized after consultation with diabetologists, nutritionists, and scientists. The mobile app has three user cases: Patient login, doctor login, and admin login. A questionnaire was designed and the feedback of patients and Physicians was taken regarding the design, presentation, content, and user-friendliness of the app based on responses obtained on the questionnaire. Results The Android version of the healthy heart mobile mobile app was developed for CVD risk stratification and risk management among type 2 diabetes mellitus patients. The dashboard of the mobile app displayed the CVD risk score and category (mild, moderate, high, or very high CVD risk; which was colored coded), health tracker to monitor medication adherence, lipid profile, diabetes control, CVD risk profile and compliance with the WHO recommendations regarding diet, physical activity and addictions, User acceptability and experience were tested for the developed healthy heart mobile app among patients and physicians. The majority of the respondents graded the design, presentation, content, and user-friendliness of the app as either excellent or good. Conclusions The mobile app for self-management and CVD risk reduction among diabetic patients was successfully developed. The paper and mobile-based CVD risk calculation and stratification were found to be a match for all the participants. The app was updated based on suggestions from the pilot study and was well-accepted by both patients and physicians.

Objectives The present study was undertaken to observe the effectiveness of electrical vestibular stimulation on the range of motion (ROM) in patients with Parkinson’s disease (PD). Methods The present study was a randomized controlled trial (ClinicalTrials.gov Identifier: NCT04450550). The study participants were assessed at three points of time. After recording baseline cognitive functions, electrical vestibular nerve stimulation was administered to the intervention group and placebo stimulation was administered to the control group for 12 weeks. Post-intervention parameters were recorded after 6 weeks and after 12 weeks after the intervention in both control and intervention groups. A total of 30 cases of PD, including both males and females were recruited in the study by convenient sampling after obtaining written informed consent. All ROM and flexibility measurements were recorded using a universal goniometer and standard protocol with help of an experienced physiotherapist at our hospital. Results There was a significant improvement in the hip internal and external rotation right and left sides. There was a significant improvement in the hip extension right and left. There was a significant improvement in the ankle plantarflexion left and ankle dorsiflexion right and left followed by the intervention. There was a significant decline in the hip internal rotation on right and left sides. There was a significant decline in the hip extension and ankle dorsiflexion on the left side. Conclusions The study results confirm the improvement of motor activities of patients with PD followed by vestibular stimulation. Further detailed studies are recommended to support the application of vestibular stimulation as an alternative therapy in the management of motor functions in patients with PD.

Objectives Single dose prophylaxis is good enough for general surgery with low risk patients. However, the evidence for the effectiveness of single dose anti-microbial prophylaxis (AMP) is not conclusive in high risk patients and spinal surgeries requiring instrumentation or the use of implants in particular. No studies have explored the various concentration of ceftriaxone in plasma and tissue as well during an ongoing spinal surgery. Therefore, the objective of study was to correlate the serum and tissue concentrations of ceftriaxone with the SSI and identify patients with increased risk of SSI. Methods It was an open label prospective study in 50 consecutive patients who underwent elective spine surgery under prophylactic cover of ceftriaxone. Serum and tissue concentration were estimated by high pressure liquid chromatography during the ongoing surgery. Results Subjects were observed for any post-operative complications including SSI. Serum (p=0.002) and tissue (p=0.012) concentrations of ceftriaxone at the closure of spinal surgery were associated with SSI. Duration of the surgery (p=0.04) and use of implants (p=0.02) were also important surgery related risk factors. Conclusions Serum and tissue concentrations of ceftriaxone at the closure and duration of surgery and instrumentation or use of implants in the spinal surgery are good predictors of SSI.

Objectives Graft-versus-host disease (GVHD) of central nervous system is an atypical and rare manifestation of chronic GVHD, presenting with a heterogeneous spectrum of signs and symptoms. Diagnosis of neurological manifestations of GVHD can be highly challenging and remain associated with dismal prognosis, significant morbidity, and reduced quality of life. Case presentation In this report, we describe a 39-year-old woman developing neurological signs and symptoms 8 months after allogeneic HSCT magnetic resonance imaging showed multifocal hyperintense lesions involving the periventricular region and frontal subcortical white matter. There was no laboratory evidence of infective or malignant etiology, and the case was diagnosed as CNS-GVHD. The patient was treated with intravenous methylprednisolone pulse therapy and the clinical conditions gradually improved. After few months, patient symptoms progressed despite the addition of high-dose intravenous immunoglobulin, tacrolimus, and a new course of high dose steroids. To engage targeted therapy, the patient underwent brain biopsy that revealed a loss of myelin fibers, perivascular and diffuse infiltration of T cells, and macrophages associated with reactive gliosis, representing a demyelinating disease. We intensified treatment with cyclophosphamide and subsequently introduced ibrutinib as salvage strategy. Despite a magnetic resonance imaging showing great regression of the demyelinating lesions, patient’s conditions deteriorated and she died 16 months after HSCT. Conclusions CNS-GVHD is a rare complication of HSCT that is difficult to diagnose. Based on our experience, brain biopsy may represent a useful diagnostic tool when the clinical features of neurological symptoms are ambiguous or in patients without evidence of preceding chronic GVHD.