Journal of Personalized Medicine

Background: There are many surgical and anesthetic factors that affect pain and the endocrine–metabolic response to trauma. The ability of anesthetic agents and neuronal blockade to modify the response to surgical trauma has been widely studied in the last few years. Objective: To evaluate if the anterior quadratus lumborum block contributes to improved surgical recovery, using as parameters analgesia, pulmonary function and neuroendocrine response to trauma. Methods: We carried out a prospective, randomized, controlled, and blinded study, in which 51 patients scheduled for laparoscopic cholecystectomy. Patients were randomly selected and assigned to 2 groups. The control group received balanced general anesthesia and venous analgesia, and the intervention group was treated under general, venous analgesia and anterior quadratus lumborum block. The parameters evaluated were: demographic data, postoperative pain, respiratory muscle pressure and inflammatory response to surgical stress with the plasma dosage of IL-6 (Interleukin 6), CRP (C-Reactive protein) and cortisol. Results: Anterior quadratus lumborum block induced the slowing of IL-6 cytokine production and a decrease in cortisol release. This effect was accompanied by the significant reduction of postoperative pain scores. Conclusion: Anterior quadratus lumborum block is an important strategy for analgesia in abdominal laparoscopic surgery and contributes to reducing the inflammatory response to surgical trauma with an early return of preoperative baseline physiological functions. Full article

Physical inactivity increases cardiometabolic risk through a variety of mechanisms, among which alterations of immunological, metabolic, and autonomic control systems may play a pivotal role. Physical inactivity is frequently associated with other factors that may further worsen prognosis. The association between physical inactivity and hypoxia is particularly interesting and characterizes several conditions—whether physiological (e.g., residing or trekking at high altitude and space flights) or pathological (e.g., chronic cardiopulmonary diseases and COVID-19). In this randomized intervention study, we investigated the combined effects of physical inactivity and hypoxia on autonomic control in eleven healthy and physically active male volunteers, both at baseline (ambulatory) conditions and, in a randomized order, hypoxic ambulatory, hypoxic bedrest, and normoxic bedrest (i.e., a simple experimental model of physical inactivity). Autoregressive spectral analysis of cardiovascular variabilities was employed to assess cardiac autonomic control. Notably, we found hypoxia to be associated with an impairment of cardiac autonomic control, especially when combined with bedrest. In particular, we observed an impairment of indices of baroreflex control, a reduction in the marker of prevalent vagal control to the SA node, and an increase in the marker of sympathetic control to vasculature. Full article

Combined oral contraceptives (COC), are among the most widely used contraceptive methods in the world today. Despite the different changes in terms of estrogen/progestogen combinations and dosages, the thromboembolic risk for a woman who takes combined oral contraceptives persists to date. Methods: The review of relevant literature and international guidelines on prescription of combined oral contraceptives made it possible to create a proposal for informed consent to be used for prescribing. Results: The several sections of our consent proposal were designed according to a rationale in order to cover all the aspects presented by worldwide guidelines: how to take, adverse effects, advertisements, extra-contraceptive benefits and effects, a checklist for condition at risk of thromboembolism, the signature of the woman. Conclusions: An informed consent to standardize combined oral contraceptives prescription can improve women’s eligibility, mitigate thromboembolic risk, and assure legal protection to healthcare providers. In this systematic review in particular, we refer to the Italian medical–legal scenario, to which our group of researchers belongs. However, the model proposed was designed in the respect of main healthcare organization guidelines, and it could be easily used by any center in the world. Full article

In this observational study, we aimed to evaluate whether bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) administered 5 or 4 days a week is able to maintain viral suppression in people living with HIV (PLHIV). We enrolled 85 patients who initiated intermittent B/F/TAF between 28 November 2018 and 30 July 2020: median (IQR) age 52 years (46–59), duration of virological suppression 9 years (3–13), CD4 633/mm³ (461–781). Median follow-up was 101 weeks (82–111). The virological success rate (no virological failure [VF]: confirmed plasma viral load [pVL] ≥ 50 copies/mL, or single pVL ≥ 200 copies/mL, or ≥50 copies/mL with ART change) was 100% (95%CI 95.8–100) and the strategy success rate (pVL < 50 copies/mL with no ART regimen change) was 92.9% (95%CI 85.3–97.4) at W48. Two VF occurred at W49 and W70, in 2 patients self-reporting poor compliance. No resistance mutation emerged at time of VF. Eight patients presented strategy discontinuation for adverse events. There was no significant change in the CD4 count, residual viraemia rate, neither body weight during follow-up, but a slight increase in CD4/CD8 ratio (p = 0.02). In conclusion, our findings suggest that B/F/TAF administered 5 or 4 days a week could maintain the control of HIV replication in virologically suppressed PLHIV while reducing cumulative exposition of ART. Full article

Introduction: While chronic kidney disease (CKD) is one of the most important contributors to mortality from non-communicable diseases, the number of nephrologists is limited worldwide. Medical cooperation is a system of cooperation between primary care physicians and nephrological institutions, consisting of nephrologists and multidisciplinary care teams. Although it has been reported that multidisciplinary care teams contribute to the prevention of worsening renal functions and cardiovascular events, there are few studies on the effect of a medical cooperation system. Methods: We aimed to evaluate the effect of medical cooperation on all-cause mortality and renal prognosis in patients with CKD. One hundred and sixty-eight patients who visited the one hundred and sixty-three clinics and seven general hospitals of Okayama city were recruited between December 2009 and September 2016, and one hundred twenty-three patients were classified into a medical cooperation group. The outcome was defined as the incidence of all-cause mortality, or renal composite outcome (end-stage renal disease or 50% eGFR decline). We evaluated the effects on renal composite outcome and pre-ESRD mortality while incorporating the competing risk for the alternate outcome into a Fine–Gray subdistribution hazard model. Results: The medical cooperation group had more patients with glomerulonephritis (35.0% vs. 2.2%) and less nephrosclerosis (35.0% vs. 64.5%) than the primary care group. Throughout the follow-up period of 5.59 ± 2.78 years, 23 participants (13.7%) died, 41 participants (24.4%) reached 50% decline in eGFR, and 37 participants (22.0%) developed end-stage renal disease (ESRD). All-cause mortality was significantly reduced by medical cooperation (sHR 0.297, 95% CI 0.105–0.835, p = 0.021). However, there was a significant association between medical cooperation and CKD progression (sHR 3.069, 95% CI 1.225–7.687, p = 0.017). Conclusion: We evaluated mortality and ESRD using a CKD cohort with a long-term observation period and concluded that medical cooperation might be expected to influence the quality of medical care in the patients with CKD. Full article

Background: tinnitus is a symptom with no specific cause known to date, and there are no associated pharmacogenomics of hearing disorders and no FDA-approved drugs for tinnitus treatment. The effectiveness of drug treatments is not reproducible on idiopathic patients and inexistent in refractory patients. Personalized treatments for these patients are a great clinical need. Our study investigated the outcome of potential alternative and complementary treatment modalities for idiopathic and refractory tinnitus patients. Methods: we were the first to evaluate the tinnitus handicap inventory (THI) score changes over the course of treatment up to 15 days after complete cessation of treatment for novel transmeatal low-level laser therapy (LLLT) modalities using light alone, as well as LLLT combined with vacuum therapy (VT), ultrasound (US), Ginkgo biloba (GB) and flunarizine dihydrochloride (FD), while also comparing all treatment outcomes with laser puncture (LP), FD alone and GB alone. Results: a positive treatment outcome (superior to a placebo effect) was achieved by using either LP or transmeatal LLLT, whereas short-term antagonistic effects of VT, US, GB and FD when combined with LLLT. For transmeatal LLLT, an improvement in the treatment outcome was observed by increasing the irradiation time from 6 min to 15 min (with 100-mW of applied laser power at 660 nm). Finally, a lasting therapeutic effect higher than the placebo was observed at 15 days after treatment upon combining LLLT with VT, GB or by using FD alone, by using the transmeatal LLLT alone or by using LP. Conclusions: LP and Transmeatal LLLT can be promising alternative treatments for idiopathic and refractory tinnitus patients. Future studies should investigate the long-term effects of LLLT in tinnitus patients, as well as the dosimetry and wavelength of transmeatal LLLT. Full article

Tramadol, an analgesic widely used for arthritic pain, is known to have adverse effects. This study investigated the association between the long-term use of tramadol for pain control and subsequent hip fractures in patients aged 60 years or older with posttraumatic osteoarthritis. This population-based retrospective cohort study included patients with posttraumatic osteoarthritis who received tramadol for pain control for more than 90 days within a 1-year period. A control cohort was enrolled using propensity score matching. The primary outcome was a new diagnosis of hip fracture requiring surgery. In total, 3093 patients were classified into each cohort. Tramadol use was identified as a risk factor for hip fracture (adjusted hazard ratio (aHR): 1.41; 95% confidence interval (CI): 1.09–1.82; p = 0.008), especially among patients aged 60–70 years (aHR: 2.11; 95% CI: 1.29–3.47; p = 0.003) and among male patients (aHR: 1.83; 95% CI: 1.24–2.70; p = 0.002). This is the first cohort study focusing on the association between long-term tramadol use and hip fracture among older adults with posttraumatic osteoarthritis. Tramadol, as a long-term pain control analgesic for older adults with posttraumatic osteoarthritis, may increase the risk of hip fracture, especially among male patients and those aged 60–70 years. Full article

Background: Medication overuse is an increasing global problem, especially for those rhinology diseases whose management requires over-the-counter drugs. This observational community pharmacy‒based study aimed to investigate the actual use of the best-selling topical nasal medications and to characterize the clinical issues underlying their query through the pharmacist’s perception. Methods: In the pilot phase, a preliminary survey was developed by a team of researchers and tested on a small sample of practitioners to assess usability and intelligibility. Eventual amendments were made according to the feedback obtained, and the final version was submitted to practitioners working in 376 pharmacies evenly distributed over the Italian territory. Results: Two groups of customers (18–30 years old and 60–75 years old) were the ones who most frequently purchased topical decongestants. The dosage applied for sympathomimetic amines was higher than recommended in up to 44.4% and the duration of use longer than 5 days in up to 31.9% of the cases. Patients’ queries of alpha agonists and topical corticosteroids resulted in significantly higher numbers than practitioners’ prescriptions. Allergic rhinitis was the most common disease affecting patients seeking sympathomimetic amines. Conclusions: The prolonged use of sympathomimetic amines in patients suffering from rhinology diseases is a significant problem that requires greater attention in terms of social education and surveillance. Full article

Silent sinus syndrome is a rare disorder characterized by ipsilateral enophthalmos and hypoglobus following a collapse of the orbital floor, in the presence of asymptomatic long-term maxillary sinusitis. It results in enophthalmos, hypoglobus and deepening of the superior palpebral sulcus. A standardized treatment protocol for this infrequent syndrome has not yet been established. The management includes restoration of maxillary sinus ventilation with functional endoscopic sinus surgery and orbital reconstruction, either concurrently or separately. In this paper, the authors presented two patients successfully treated with patient-specific implants, and intraoperative navigation. These cases highlight the benefit of computer-assisted planning and titanium patient-specific implants in the management of silent sinus syndrome. To the best of our knowledge, this is the first report that described the use of PSI with titanium spacers performed with the aid of intraoperative navigation for SSS treatment. Advantages, drawbacks of this technique and treatment alternatives currently available in the literature were also discussed. Full article

The purpose of the study was to examine the urinary levels of kidney injury molecule-1 (KIM-1) and angiopoietin-like protein-4 (ANGPTL-4) in individuals with diabetic kidney disease (DKD) and their association with established DKD diagnostic markers such as albuminuria and estimated glomerular filtration rate (eGFR). Levels of ANGPTL-4 and KIM-1 were estimated in urine samples. A total of 135 participants were recruited into three groups: 45 diabetes type 2 patients in the control group and 90 DKD patients in two disease groups. Concentrations of ANGPTL-4 and KIM-1 were conclusively related to the urinary albumin–creatinine ratio (UACR). Also, the levels of both ANGPTL-4 and KIM-1 were negatively associated with the eGFR. Multivariable Poisson regression analysis showed that urinary ANGPTL-4 (PR: 3.40; 95% CI: 2.32 to 4.98; p < 0.001) and KIM-1 (PR: 1.25; 95% CI: 1.14 to 1.38; p < 0.001) were prevalent in DKD patients. Receiver operating characteristic (ROC) analysis of urinary ANGPTL-4 and KIM-1 in the combined form resulted in an area under curve (AUC) of 0.967 (95%CI: 0.932–1.000; p < 0.0001) in the microalbuminuria group and 1 (95%CI: 1.000–1.000; p < 0.0001) in the macroalbuminuria group. The association of urinary levels of ANGPTL-4 and KIM-1 with UACR and eGFR and significant prevalence in the diabetic kidney disease population illustrates the diagnostic potential of these biomarkers. Full article

Colorectal cancer (CRC) is a major public health issue, and there are limited studies on the association between 17β-hydroxysteroid dehydrogenase type 4 (HSD17B4) polymorphism and CRC. We used two national databases from Taiwan to examine whether HSD17B4 rs721673, rs721675, and alcohol intake were independently and interactively correlated with CRC development. We linked the Taiwan Biobank (TWB) participants’ health and lifestyle information and genotypic data from 2012 to 2018 to the National Health Insurance Database (NHIRD) to confirm their medical records. We performed a genome-wide association study (GWAS) using data from 145 new incident CRC cases and matched 1316 healthy, non-CRC individuals. We calculated the odds ratios (OR) and 95% confidence intervals (CI) for CRC based on multiple logistic regression analyses. HSD17B4 rs721673 and rs721675 on chromosome 5 were significantly and positively correlated with CRC (rs721673 A > G, aOR = 2.62, p = 2.90 × 10⁻⁸; rs721675 A > T, aOR = 2.61, p = 1.01 × 10⁻⁶). Within the high-risk genotypes, significantly higher ORs were observed among the alcohol intake group. Our results demonstrated that the rs721673 and rs721675 risk genotypes of HSD17B4 might increase the risk of CRC development in Taiwanese adults, especially those with alcohol consumption habits. Full article

Background: Long-term survival after emergency colorectal cancer surgery is low, and its estimation is most frequently neglected, with priority given to the immediate prognosis. This study aimed to propose an effective nomogram to predict overall survival in these patients. Materials and methods: We retrospectively studied 437 patients who underwent emergency surgery for colorectal cancer between 2008 and 2019, in whom we analyzed the clinical, paraclinical, and surgical parameters. Results: Only 30 patients (6.86%) survived until the end of the study. We identified the risk factors through the univariate Cox regression analysis and a multivariate Cox regression model. The model included the following eight independent prognostic factors: age > 63 years, Charlson score > 4, revised cardiac risk index (RCRI), LMR (lymphocytes/neutrophils ratio), tumor site, macroscopic tumoral invasion, surgery type, and lymph node dissection (p < 0.05 for all), with an AUC (area under the curve) of 0.831, with an ideal agreement between the predicted and observed probabilities. On this basis, we constructed a nomogram for prediction of overall survival. Conclusions: The nomogram created, on the basis of a multivariate logistic regression model, has a good individual prediction of overall survival for patients with emergency surgery for colon cancer and may support clinicians when informing patients about prognosis. Full article

The majority of animal studies on methylphenidate (MP) use intraperitoneal (IP) injections, subcutaneous (SC) injections, or the oral gavage route of administration. While all these methods allow for delivery of MP, it is the oral route that is clinically relevant. IP injections commonly deliver an immediate and maximum dose of MP due to their quick absorption. This quick-localized effect can give timely results but will only display a small window of the psychostimulant’s effects on the animal model. On the opposite side of the spectrum, a SC injection does not accurately represent the pathophysiology of an oral exposure because the metabolic rate of the drug would be much slower. The oral-gavage method, while providing an oral route, possesses some adverse effects such as potential animal injury and can be stressful to the animal compared to voluntary drinking. It is thus important to allow the animal to have free consumption of MP, and drinking it to more accurately mirror human treatment. The use of a two-bottle drinking method allows for this. Rodents typically have a faster metabolism than humans, which means this needs to be considered when administering MP orally while reaching target pharmacokinetic levels in plasma. With this oral two-bottle approach, the pathophysiological effects of MP on development, behavior, neurochemistry and brain function can be studied. The present review summarizes these effects of oral MP which have important implications in medicine. Full article

Direct-to-consumer (DTC) genetic tests have generated considerable scholarly attention and public intrigue. Although the current consumer genetic testing regime relies on the reporting of individual variants of interest to consumers, there has recently been interest in the possibility of integrating polygenic scores (PGS), which aggregate genetic liability for disease across the entire genome. While PGS have thus far been extensively explored as clinical and public health tools, the use of PGS in consumer genetic testing has not yet received systematic attention, even though they are already in use for some consumer genetic tests. In this narrative review, we highlight the ethical, legal, and social implications of the use of PGS in DTC genetic tests and synthesize existing solutions to these concerns. We organize these concerns into three domains: (1) industry variation; (2) privacy and commercialization; and (3) patient safety and risk. While previously expressed concerns in these domains will remain relevant, the emergence of PGS-based DTC genetic tests raises challenges that will require novel approaches. Full article

Background: The effect of intravitreal conbercept (IVC) before pars plana vitrectomy (PPV) on surgical complications in patients with proliferative diabetic retinopathy (PDR) was observed. Methods: A total of 152 patients with PDR operated on in Jiangsu Provincial People’s Hospital from November 2019 to November 2020 were divided into two groups: 124 patients in the preoperative intravitreal conbercept injection + PPV group (IVC group) and 28 patients in the PPV only group (No-IVC group). Vitreous samples were collected in all eyes of patients who underwent vitrectomy, and the content of VEGF-A was measured by Luminex. The effect of conbercept on intraoperative and postoperative complications of PDR was assessed. Results: The content of VEGF in the vitreous of the IVC group was significantly lower than that in the No-IVC group (64.50 ± 58.40 pg/mL vs. 805.17 ± 417.60 pg/mL, p < 0.001). During postoperative follow-up, early postoperative vitreous hemorrhage (VH) occurred in 13 of 142 eyes (9.15%). Compared with the No-IVC group, PDR patients with VH and fibrovascular membrane (FVM) or high complexity in the IVC group had lower intraoperative bleeding rates (p < 0.05). The early postoperative hemorrhage rate in the IVC group was lower than in the No-IVC group (6.03% vs. 23.08%, p < 0.05). The number of intraoperative electrocoagulation and iatrogenic retinal holes in the IVC group was significantly lower than in the No-IVC group (p < 0.05). There were no significant differences in intraocular hypertension and NVG numbers between the two groups. Visual acuity in both groups improved after PPV surgery, reaching the highest level in the 3rd month after the operation. Conclusions: IVC before PPV can reduce the level of VEGF-A in the vitreous body and reduce surgical complications. Full article

Pediatric Crohn’s disease (CD) presents a distinct phenotype from adult-onset disease. A dysregulated immune response is critical in CD pathogenesis; thus, it is clinically important to describe immune cell alterations and to identify a new molecular classification for pediatric CD. To this end, in this study, a RNA-seq derived dataset GSE101794—which contains the expression profiles of 254 treatment-naïve pediatric CD samples, including CIBERSORTx and weighted gene-co-expression network analysis (WGCNA)—were performed to estimate the ratio of immune cells and to identify modules and genes related to specific immune cell infiltration, respectively. Hub genes derived from WGCNA were further employed to create a molecular classification using unsupervised K-means clustering. In the pediatric CD samples, it was found that M2 macrophages, CD4⁺ memory resting T cells, CD8⁺ T cells, and resting mast cells were the most prominent immune cells in intestinal tissues. Then, 985 up-regulated genes and 860 down-regulated genes were identified in samples with high immune cell infiltration. Of these differential genes, 10 hub genes (APOA1, CYB5A, XPNPEP2, SLC1A7, SLC4A6, LIPE, G6PC, AGXT2, SLC13A1, and SOAT2) were associated with CD8⁺T cell infiltration. Clinically, the higher expression of these 10 hub genes was strongly associated with an earlier age of CD onset and colonic-type CD. Furthermore, based on these key genes, pediatric CD could be classified into three molecular subtypes, displaying a different immune landscape. Altogether, this in silico analysis provides a novel insight into the immune signature of pediatric CD, and a new classification of pediatric CD is presented, which may help us develop more personalized disease management and treatments for pediatric CD. Full article

Purpose: A retrospective study is presented to correlate the inter-judge consistency for the different psycho-perceptual parameters of the recently proposed Impression Noise Fluency Voicing (INFVo) perceptual rating scale for substitution voices, and the vocal function as perceived by the patient. Methods: The scale Voice-Related Quality of Life (V-RQoL) and the Self Evaluation of Communication Experiences After Laryngectomy scale (SECEL)—a self-evaluation questionnaire of communicative experience after laryngectomy surgery—were administered to 89 total laryngectomees, subdivided in four groups depending on their type of alaryngeal voice (i.e., tracheoesophageal and esophageal speakers, electro larynx users, voiceless patients), in order to evaluate the impact of the impairment of the phonatory function on the quality of life. Results: No significant differences exist among the various groups on their perception of QoL using subjective questionnaires, whereas the INFVo scale has proven to be a useful tool for the description and analysis of the psychoacoustic characteristics of the vocal signal and a reliable instrument to correctly classify the patients. It is also notable that the judgement of the patients on their own voice and those of the referees are highly significant. Conclusion: Although speech rehabilitation for the acquisition of a substitution voice offers a new way of communication for the laryngectomized patients, nonetheless, their QoL is not significantly related to the type of substitution voice. Therefore, improving the patient’s adaptation to the new phonatory condition is mandatory. Full article

With an ever-growing knowledge in various disciplines of medicine and with rapidly evolving new techniques and operative methods in plastic surgery, it is obvious that it becomes more and more difficult to keep up with all the developments in this field at any time [...] Full article