Journal of Clinical Medicine

Weber, Christian D.;Lefering, Rolf;Sellei, Richard M.;Horst, Klemens;Migliorini, Filippo;Hildebrand, Frank;TraumaRegister DGU,

doi: 10.3390/jcm11030472pmid: 35159925

Introduction: Traumatic hip dislocations (THDs) are severe injuries associated with considerable morbidity. Delayed recognition of fracture dislocations and neurovascular deficits have been proposed to cause deleterious long-term clinical outcomes. Therefore, in this study, we aimed to identify characteristics of epidemiology, injury mechanisms, and associated injuries to identify patients at risk. Methods: For this study based on the TraumaRegister DGU® (January 2002–December 2017), the inclusion criterion was an Injury Severity Score (ISS) ≥9 points. Exclusion criteria were an isolated head injury and early transfer to another hospital. The THD group was compared to a control group without hip dislocation. The ISS and New ISS were used for injury severity and the Abbreviated Injury Scale for associated injuries classification. Univariate and logistic regression analyses were performed. Results: The final study cohort comprised n = 170,934 major trauma patients. We identified 1359 individuals (0.8%) with THD; 12 patients had sustained bilateral hip dislocations. Patients with THD were predominantly male (79.5%, mean age 43 years, mean ISS 22.4 points). Aortic injuries (2.1% vs. 0.9%, p ≤ 0.001) were observed more frequently in the THD group. Among the predictors for THDs were specific injury mechanisms, including motor vehicle accidents (odds ratio (OR) 2.98, 95% confidence interval (CI) 2.57–3.45, p ≤ 0.001), motorcycle accidents (OR 1.99, 95% CI 1.66–2.39, p ≤ 0.001), and suicide attempts (OR 1.36, 95% CI 1.06–1.75, p = 0.016). Despite a lower rate of head injuries and a comparable level of care measured by trauma center admission, both intensive care unit and total hospital stay were prolonged in patients with THD. Conclusions: Since early diagnosis, as well as timely and sufficient treatment, of THDs are of high relevance for long-term outcomes of severely injured individuals, knowledge of patients at risk for this injury pattern is of utmost importance. THDs are frequently related to high-energy mechanisms and associated with severe concomitant injuries in major trauma patients.

Del Amo, Cristina;Perez-Valle, Arantza;Atilano, Leire;Andia, Isabel

doi: 10.3390/jcm11030473pmid: 35159924

Platelets and their secretory products play an important role in determining the balance between tissue repair and tissue damage. To obtain novel insights into the molecular composition of platelet-rich plasma (PRP) and contextualize them in knee osteoarthritis (OA), two different plasma formulations, namely PRP and platelet-poor plasma (PPP), were prepared from six healthy donors following a biobank-automated protocol. Inter-donor differences were analyzed, and pools were created before performing multiplexing protein arrays. In addition, PRP and PPP were prepared from six patients following our in-house protocols. Supernatants from PRP and PPP were harvested one hour after calcium chloride activation. Multiplexing protein arrays were performed in parallel for all plasma formulations. Results were normalized to fold change in relation to PPP and examined using Ingenuity Pathway Analysis Software. Bioinformatic predictions showed that PRPs constitute a signaling system with interrelated networks of inflammatory and angiogenic proteins, including but not limited to interleukin-6 and -8 (IL-6, IL-8), insulin like growth factor 1 (IGF-1), transforming growth factor beta, (TGF-b), and vascular endothelial growth factor (VEGF) signaling, underlying biological actions. Predictions of canonical systems activated with PRP molecules include various inflammatory pathways, including high-mobility group box protein (HMGB1) and interleukin 17 (IL-17) signaling, neuroinflammation, and nuclear factor-kappa b (NF-κB) pathways. Eventually, according to these predictions and OA evolving knowledge, selected PRP formulations should be tailored to modulate different inflammatory phenotypes, i.e., meta-inflammation, inflame-aging or posttraumatic inflammatory osteoarthritis. However, further research to discriminate the peculiarities of autologous versus allogeneic formulations and their effects on the various OA inflammatory phenotypes is needed to foster PRPs.

López-Moral, Mateo;Molines-Barroso, Raúl J.;Sanz-Corbalán, Irene;Tardáguila-García, Aroa;García-Madrid, Marta;Lázaro-Martínez, José Luis

doi: 10.3390/jcm11030474pmid: 35159926

Background: To identify differences in radiographic outcomes in weight-bearing lateral X-ray to predict the probability of ulceration in patients with midfoot Charcot neuroarthropathy (CN) differentiated by lateral and medial column deformities. Methods: Thirty-five patients who suffered from CN midfoot deformity participated in this 1 year prospective study in a specialized diabetic foot unit. Lateral talar-first metatarsal angle, calcaneal pitch, and cuboid height were performed by digital radiographs in the weight-bearing lateral view. Patients were followed up for 1 year or until an ulcer ulceration event occurred in the midfoot region. Results: ROC analyses showed that all patients with medial pattern deformity that developed a midfoot ulcer had a lateral talar-first metatarsal angle greater (negative) than −27.5 degrees (°). All patients with lateral pattern deformity that developed a midfoot ulcer had a calcaneal pitch greater (more negative) than −5° and a cuboid height greater (more negative) than −1.5°. Conclusions: Lateral talar-first metatarsal angle was the greatest predictor of midfoot ulceration, with greater than −27.5° measurement correlating with ulceration occurrence in patients with medial deformity. Calcaneal pitch and cuboid height were the greatest predictors of midfoot ulceration with greater than −5 and −1.5°, respectively in patients with CN lateral deformity.

Caso, Valentina Maria;Sperlongano, Simona;Liccardo, Biagio;Romeo, Emanuele;Padula, Sergio;Arenga, Fortunato;D’Andrea, Antonello;Caso, Pio;Golino, Paolo;Nigro, Gerardo;Russo, Vincenzo

doi: 10.3390/jcm11030475pmid: 35159928

PCSK9 inhibitors (PCSK9i) are monoclonal antibodies that have been shown to be effective in reducing both LDL cholesterol (LDL-C) values and major cardiovascular events in patients at high cardiovascular risk. Adherence to PCSK9i is critical for the success of the treatment. The aim of the present study is to evaluate patients’ adherence to PCSK9i during the COVID-19 pandemic. Patients referred to the Cardiac Diagnostic Unit of the University of Campania “Luigi Vanvitelli” Naples, taking PCSK9i, and who missed the cardiological follow-up visit during the first national COVID-19 lockdown (9 March–17 May 2020), were included. Each patient underwent medical teleconsultation to collect current clinical conditions, adherence to drug treatments, and lipid profile laboratory tests. Among 151 eligible patients, 20 were excluded for missing or untraceable telephone numbers and one for refusing to join the interview. The selected study population consisted of 130 patients (64 ± 9 years, 68% males), of whom 11 (8.5%) reported a temporary interruption of the PCSK-9 therapy for a mean period of 65 ± 1.5 days. The non-adherent patients showed a marked increase in LDL-C than in the pre-pandemic period (90.8 ± 6.0 vs. 54.4 ± 7.7 mg/dL, p < 0.0001), and 82% of patients moved out of the LDL-C therapeutic range. The non-adherent group was more likely to have a very high cardiovascular risk compared to the adherent group (81.8 vs. 33.6%, p < 0.001). Causes of interruption included drug prescription failure (63.6%) due to temporary interruption of the non-urgent outpatient visits and failure in drug withdrawal (36.4%) due to patients’ fear of becoming infected during the pandemic. The COVID-19 lockdown caused a remarkable lack of adherence to PCSK9i therapy, risking negative implications for the health status of patients at high cardiovascular risk. Facilitating patients’ access to PCSK9i and enhancing telemedicine seem to be effective strategies to ensure the continuity of care and appropriate management of these patients.

Delgado-Barriga, Katty;Medina, Carmen;Gomez-Quiles, Luis;Marco-Domenech, Santiago F.;Escrig, Javier;Llueca, Antoni

doi: 10.3390/jcm11030476pmid: 35159927

To compare the diagnostic performance of routine CT (rCT), CT enterography (CTE) and intraoperative quantification of PCI to surgical and pathological reference standards in patients with advanced ovarian cancer, a retrospective study of 122 patients who underwent cytoreduction surgery for ovarian peritoneal carcinomatosis was conducted. Radiological, surgical, and pathological PCIs were obtained from the corresponding reports, and the latter two were considered reference standards. The radiological techniques used were rCT: 64 MDCT (32 × 1 mm) (100 mL iopromide 370 i.v., 800 mL water p.o.), and CTE: 64 MDCT (64 × 0.5 mm) (130 mL iopromide 370 i.v., 1800 mL mannitol solution p.o., 20 mg buscopan i.v.). Data were grouped by imaging technique and analyzed using total PCI and stratified by tumor burden (low-PCI < 10, high-PCI > 20). Agreement, diagnostic performance and degree of cytoreduction were evaluated. Disappointing results for rCT and CTE were obtained when using a surgical referent, but better diagnostic performance and concordance (0.86 vs. 0.78 vs. 0.62, p < 0.05) was observed when using a pathological referent—surgical PCI overestimates and overstaged patients. PCI is underestimated by rCT rather than CTE. For high-PCI, the ROC curve was mediocre for CTE and useless for rCT, as it failed to identify any cases. For low-PCI, the ROC was excellent (86% CTE vs. 75% rCT). In four cases with low-PCI as determined by rCT, cytoreduction was suboptimal. CTE has a better diagnostic performance than rCT in quantifying PCI in patients with advanced ovarian cancer, suggesting that CTE should be used as the initial technique. Surgical-PCI could be considered as an imperfect standard reference.

Baggiano, Andrea;Italiano, Gianpiero;Guglielmo, Marco;Fusini, Laura;Guaricci, Andrea Igoren;Maragna, Riccardo;Giacari, Carlo Maria;Mushtaq, Saima;Conte, Edoardo;Annoni, Andrea Daniele;Formenti, Alberto;Mancini, Maria Elisabetta;Andreini, Daniele;Rabbat, Mark;Pepi, Mauro;Pontone, Gianluca

Cao, Ke;Verspoor, Karin;Sahebjada, Srujana;Baird, Paul N.

doi: 10.3390/jcm11030478pmid: 35159930

(1) Background: The objective of this review was to synthesize available data on the use of machine learning to evaluate its accuracy (as determined by pooled sensitivity and specificity) in detecting keratoconus (KC), and measure reporting completeness of machine learning models in KC based on TRIPOD (the transparent reporting of multivariable prediction models for individual prognosis or diagnosis) statement. (2) Methods: Two independent reviewers searched the electronic databases for all potential articles on machine learning and KC published prior to 2021. The TRIPOD 29-item checklist was used to evaluate the adherence to reporting guidelines of the studies, and the adherence rate to each item was computed. We conducted a meta-analysis to determine the pooled sensitivity and specificity of machine learning models for detecting KC. (3) Results: Thirty-five studies were included in this review. Thirty studies evaluated machine learning models for detecting KC eyes from controls and 14 studies evaluated machine learning models for detecting early KC eyes from controls. The pooled sensitivity for detecting KC was 0.970 (95% CI 0.949–0.982), with a pooled specificity of 0.985 (95% CI 0.971–0.993), whereas the pooled sensitivity of detecting early KC was 0.882 (95% CI 0.822–0.923), with a pooled specificity of 0.947 (95% CI 0.914–0.967). Between 3% and 48% of TRIPOD items were adhered to in studies, and the average (median) adherence rate for a single TRIPOD item was 23% across all studies. (4) Conclusions: Application of machine learning model has the potential to make the diagnosis and monitoring of KC more efficient, resulting in reduced vision loss to the patients. This review provides current information on the machine learning models that have been developed for detecting KC and early KC. Presently, the machine learning models performed poorly in identifying early KC from control eyes and many of these research studies did not follow established reporting standards, thus resulting in the failure of these clinical translation of these machine learning models. We present possible approaches for future studies for improvement in studies related to both KC and early KC models to more efficiently and widely utilize machine learning models for diagnostic process.

Henein, Michael Y.;Cameli, Matteo;Pastore, Maria Concetta;Mandoli, Giulia Elena

doi: 10.3390/jcm11030479pmid: 35159931

The COVID-19 pandemic is a global health issue that has so far affected over 250 million people worldwide [...]

Gałecki, Piotr;Samochowiec, Jerzy;Mikułowska, Magdalena;Szulc, Agata

doi: 10.3390/jcm11030480pmid: 35159935

(1) Background: Major depressive disorder (MDD) is one of the most prevalent psychiatric disorders worldwide. Although several antidepressant drugs have been developed, up to 30% of patients fail to achieve remission, and acute remission rates decrease with the number of treatment steps required. The aim of the current project was to estimate and describe the population of treatment-resistant depression (TRD) patients in outpatient clinics in Poland. (2) Methods: The project involved a representative sample of psychiatrists working in outpatient clinics, chosen through a process of quota random sampling. The doctors completed two questionnaires on a consecutive series of patients with MDD, which captured the patients’ demographics, comorbidities, and medical histories. TRD was defined as no improvement seen after a minimum of two different antidepressant drug therapies applied in sufficient doses for a minimum of 4 weeks each. The data were weighted and extrapolated to the population of TRD outpatients in Poland. (3) Results: A total of 76 psychiatrists described 1781 MDD patients, out of which 396 fulfilled the criteria of TRD. The TRD patients constituted 25.2% of all MDD patients, which led to the number of TRD outpatients in Poland being estimated at 34,800. The demographics, comorbidities, medical histories, and histories of treatment of Polish TRD patients were described. In our sample of the TRD population (mean age: 45.6 ± 13.1 years; female: 64%), the patients had experienced 2.1 ± 1.6 depressive episodes (including the current one), and the mean duration of the current episode was 4.8 ± 4.4 months. In terms of treatment strategies, most patients (around 70%) received monotherapy during the first three therapies, while combination antidepressant drugs (ADs) were applied more often from the fourth line of treatment. The use of additional medications and augmentation was reported in only up to one third of the TRD patients. During all of the treatment steps, patients most often received a selective serotonin reuptake inhibitor (SSRI) and a serotonin norepinephrine reuptake inhibitor (SNRI). (4) Conclusions: TRD is a serious problem, affecting approximately one fourth of all depressive patients and nearly 35,000 Poles.

Grebenstein, Patricia E.;Erickson, Paige;Grace, Martha;Kotz, Catherine M.

doi: 10.3390/jcm11030481pmid: 35159932

Obesity is a leading cause of preventable death in the United States. Currently approved pharmacotherapies for the treatment of obesity are associated with rebound weight gain, negative side effects, and the potential for abuse. There is a need for new treatments with fewer side effects. Minor tobacco alkaloids (MTAs) are potential candidates for novel obesity pharmacotherapies. These alkaloids are structurally related to nicotine, which can help reduce body weight, but without the same addictive potential. The purpose of the current study was to examine the effects of three MTAs (nornicotine, anatabine, and anabasine) and nicotine on weight gain, body composition, chow intake, and physical activity. We hypothesized that the MTAs and nicotine would reduce weight gain through reductions in chow intake and increases in physical activity. To test this, male Sprague Dawley rats were housed in metabolic phenotyping chambers. Following acclimation to these chambers and to (subcutaneous (sc)) injections of saline, animals received daily injections (sc) of nornicotine, anabasine, anatabine, or nicotine for one week. Compared to saline-injected animals that gained body weight and body fat during the treatment phase, injections of nornicotine and anatabine prevented additional weight gain, alongside reductions in body fat. Rats receiving anabasine and nicotine gained body weight at a slower rate relative to rats receiving saline injections, and body fat remained unchanged. All compounds reduced the intake of chow pellets. Nornicotine and nicotine produced consistent increases in physical activity 6 h post-injection, whereas anabasine’s and anatabine’s effects on physical activity were more transient. These results show that short-term, daily administration of nornicotine, anabasine, and anatabine has positive effects on weight loss, through reductions in body fat and food intake and increases in physical activity. Together, these findings suggest that MTAs are worthy of further investigations as anti-obesity pharmacotherapies.