J. Clin. Med., Volume 12, Issue 5 (March-1 2023) – 377 articles

Holmium laser enucleation of the prostate (HoLEP) constitutes an established technique for treating patients with symptomatic bladder outlet obstruction. Most surgeons perform surgeries using high-power (HP) settings. Nevertheless, HP laser machines are costly, require high-power sockets, and may be linked with increased postoperative dysuria. Low-power (LP) lasers could overcome these drawbacks without compromising postoperative outcomes. Nevertheless, there is a paucity of data regarding LP laser settings during HoLEP, as most endourologists are hesitant to apply them in their clinical practice. We aimed to provide an up-to-date narrative looking at the impact of LP settings in HoLEP and comparing LP with HP HoLEP. According to current evidence, intra- and post-operative outcomes as well as complication rates are independent of the laser power level. LP HoLEP is feasible, safe, and effective and may improve postoperative irritative and storage symptoms. Full article

Background: We have previously reported that the incidence of postoperative conduction disorders, especially left bundle branch block (LBBB), after implantation of a rapid deployment Intuity™ Elite aortic valve prosthesis (Edwards Lifesciences, Irvine, CA, USA), was significantly increased compared with conventional aortic valve replacement. We were now interested in how these disorders behaved at intermediate follow-up. Methods: All 87 patients who had undergone surgical aortic valve replacement (SAVR) using the rapid deployment Intuity™ Elite prosthesis and were shown to have conduction disorders at the time of hospital discharge were followed up after surgery. These patients’ ECGs were recorded at least 1 year after surgery, and the persistence of the new postoperative conduction disorders was assessed. Results: At hospital discharge, 48.1% of the patients had developed new postoperative conduction disorders, with LBBB being the predominant conduction disturbance (36.5%). At medium-term follow-up (526 days, standard deviation (SD) = 169.6, standard error (SE) = 19.3 days, respectively), 44% of the new LBBB and 50% of the new right bundle branch block (RBBB) had disappeared. There was no new atrio-ventricular block III (AVB III) that occurred. One new pacemaker (PM) was implanted during follow-up because of AVB II Mobitz type II. Conclusions: At medium-term follow-up after the implantation of a rapid deployment Intuity™ Elite aortic valve prosthesis, the number of new postoperative conduction disorders, especially LBBB, has considerably decreased but remains high. The incidence of postoperative AV block III remained stable. Full article

Patients ≥ 75 years of age account for about one third of hospitalizations for acute coronary syndromes (ACS). Since the latest European Society of Cardiology guidelines recommend that older ACS patients use the same diagnostic and interventional strategies used by the younger ones, most elderly patients are currently treated invasively. Therefore, an appropriate dual antiplatelet therapy (DAPT) is indicated as part of the secondary prevention strategy to be implemented in such patients. The choice of the composition and duration of DAPT should be tailored on an individual basis, after careful assessment of the thrombotic and bleeding risk of each patient. Advanced age is a main risk factor for bleeding. Recent data show that in patients of high bleeding risk short DAPT (1 to 3 months) is associated with decreased bleeding complications and similar thrombotic events, as compared to standard 12-month DAPT. Clopidogrel seems the preferable P2Y12 inhibitor, due to a better safety profile than ticagrelor. When the bleeding risk is associated with a high thrombotic risk (a circumstance present in about two thirds of older ACS patients) it is important to tailor the treatment by taking into account the fact that the thrombotic risk is high during the first months after the index event and then wanes gradually over time, whereas the bleeding risk remains constant. Under these circumstances, a de-escalation strategy seems reasonable, starting with DAPT that includes aspirin and low-dose prasugrel (a more potent and reliable P2Y12 inhibitor than clopidogrel) then switching after 2–3 months to DAPT with aspirin and clopidogrel for up to 12 months. Full article

Introduction The suitability of adjuvant therapy (AT) in patients with stage IB non-small cell lung cancer (NSCLC) is still under debate considering the cost–benefit ratio between improvement in survival and side effects. We retrospectively evaluated survival and incidence of recurrence in radically resected stage IB NSCLC, to determine whether AT could significantly improve prognosis. Methods Between 1998 and 2020, 4692 consecutive patients underwent lobectomy and systematic lymphadenectomy for NSCLC. Two hundred nineteen patients were pathological T2aN0M0 (>3 and ≤4 cm) NSCLC 8th TNM. None received preoperative or AT. Overall survival (OS), cancer specific survival (CSS) and the cumulative incidence of relapse were plotted and log-rank or Gray’s tests were used to assess the difference in outcome between groups. Results The most frequent histology was adenocarcinoma (66.7%). Median OS was 146 months. The 5-, 10-, and 15-year OS rates were 79%, 60%, and 47%, whereas the 5-, 10-, and 15-year CSS were 88%, 85%, and 83%, respectively. OS was significantly related to age (p < 0.001) and cardiovascular comorbidities (p = 0.04), whereas number of LNs removed was an independent prognostic factor of CSS (p = 0.02). Cumulative incidence of relapse at 5-, 10-, and 15-year were 23%, 31%, and 32%, respectively, and significantly related to the number of LNs removed (p = 0.01). Patients with more than 20 LNs removed and clinical stage I had a significantly lower relapse (p = 0.02). Conclusions Excellent CSS, up to 83% at 15-year, and relatively low risk of recurrence for stage IB NSCLC (8th TNM) patients suggested that AT for those patients could be reserved only for very selected high-risk cases. Full article

Hemophilia A is a rare congenital bleeding disorder caused by a deficiency of functionally active coagulation factor VIII (FVIII). Most patients with the severe form of the disease require FVIII replacement therapies, which are often associated with the development of neutralizing antibodies against FVIII. Why some patients develop neutralizing antibodies while others do not is not fully understood. Previously, we could demonstrate that the analysis of FVIII-induced gene expression signatures in peripheral blood mononuclear cells (PBMC) obtained from patients exposed to FVIII replacement therapies provides novel insights into underlying immune mechanisms regulating the development of different populations of FVIII-specific antibodies. The aim of the study described in this manuscript was the development of training and qualification test procedures to enable local operators in different European and US clinical Hemophilia Treatment Centers (HTC) to produce reliable and valid data for antigen-induced gene expression signatures in PBMC obtained from small blood volumes. For this purpose, we used the model antigen Cytomegalovirus (CMV) phosphoprotein (pp) 65. We trained and qualified 39 local HTC operators from 15 clinical sites in Europe and the US, of whom 31 operators passed the qualification at first attempt, and eight operators passed at the second attempt.  Full article

Sleep disturbances are strongly associated with mild traumatic brain injury (mTBI) and post-traumatic stress disorder (PTSD). PTSD and mTBI have been linked to alterations in white matter (WM) microstructure, but whether poor sleep quality has a compounding effect on WM remains largely unknown. We evaluated sleep and diffusion magnetic resonance imaging (dMRI) data from 180 male post-9/11 veterans diagnosed with (1) PTSD (n = 38), (2) mTBI (n = 25), (3) comorbid PTSD+mTBI (n = 94), and (4) a control group with neither PTSD nor mTBI (n = 23). We compared sleep quality (Pittsburgh Sleep Quality Index, PSQI) between groups using ANCOVAs and calculated regression and mediation models to assess associations between PTSD, mTBI, sleep quality, and WM. Veterans with PTSD and comorbid PTSD+mTBI reported poorer sleep quality than those with mTBI or no history of PTSD or mTBI (p = 0.012 to <0.001). Poor sleep quality was associated with abnormal WM microstructure in veterans with comorbid PTSD+mTBI (p < 0.001). Most importantly, poor sleep quality fully mediated the association between greater PTSD symptom severity and impaired WM microstructure (p < 0.001). Our findings highlight the significant impact of sleep disturbances on brain health in veterans with PTSD+mTBI, calling for sleep-targeted interventions. Full article

Background: Sarcopenia is the core component of frailty; however, its role in patients undergoing transcatheter aortic valve replacement (TAVR) is a matter of debate. The Toronto Aortic Stenosis Quality of Life Questionnaire (TASQ) is a validated instrument for assessing quality of life (QoL) in patients with severe aortic stenosis (AS). Aims: We aim to evaluate the QoL of sarcopenic and non-sarcopenic patients with severe AS undergoing TAVR. Methods: TASQ was prospectively administered to patients undergoing TAVR. All patients completed the TASQ before TAVR and at a 3-month follow-up. The study population was divided in two groups according to sarcopenic status. The primary endpoint was the TASQ score in the sarcopenic and non-sarcopenic cohorts. Results: In total, 99 patients were eligible for the analysis. In both sarcopenic (n = 56) and non-sarcopenic (n = 43) cohorts, significant changes were observed in the overall TASQ score and in all but one (i.e., health expectations) of the individual domains (p < 0.01). Sarcopenic and non-sarcopenic patients showed substantial improvements across TASQ subscores. The mean change in overall TASQ score at three months revealed a significant improvement in both cohorts (p < 0.01). Health expectations worsened in sarcopenic patients at the 3-month follow-up (p = 0.06). Conclusions: The TASQ questionnaire revealed changes in QoL after TAVR, regardless of patients’ sarcopenic status. Health status improved substantially in both sarcopenic and non-sarcopenic patients following TAVR. Lack of improvement in health expectations seems to depend on patients’ expectations regarding the procedure and specific aspects in the evaluation of the outcome. Full article

Background: During the past decade, the Perimount Magna Ease (PME) bioprosthesis has been implanted worldwide for aortic valve replacement (AVR). Recently, the INSPIRIS Resilia (IR) valve has been introduced as the newest generation of pericardial bioprostheses. However, few data have been reported about patients ≤70 years, and no comparisons in terms of hemodynamic performance between these two bioprostheses have been ever reported. Methods: Patients aged <70 years undergoing AVR were considered for comparison between PME (n = 238) and IR (n = 192). Propensity score (PS) matching was performed by logistic regression with adjustment for eight key baseline variables. The two prostheses were compared in terms of hemodynamic performances up to 3 years postoperatively. Sub-analysis according to prosthetic size-category was accomplished. Results: A total of 122 pairs with similar baseline characteristics were obtained from the PS-matching. The two prostheses showed comparable hemodynamic performances at one year (Gmean: 11.3 ± 3.5 mmHg vs. 11.9 ± 5.4 mmHg; p = 0.8) and at 3 years postoperatively (Gmean: 12.2 ± 7.9 mmHg vs. 12.8 ± 5.2 mmHg for; p = 0.3). The sub-analysis of size-category confirmed no statistical differences concerning the hemodynamic performances for each annulus size. Conclusions: This first PS-matched analysis demonstrated that the newly developed IR valve achieves the same safety and efficacy of the PME valve during mid-term follow-up in patients aged <70 years. Full article

Background: Distal radius fractures (DRFs) in the elderly are common. Recently, the efficacy of operative treatment of displaced DRFs in patients above 65 years of age has been questioned and it has been suggested that non-operative treatment should be the gold standard. However, the complications and functional outcome of displaced vs. minimally and non-displaced DRFs in the elderly has not been evaluated yet. The aim of the present study was to compare non-operatively treated displaced DRFs vs. minimally and non-displaced DRFs in terms of complications, PROMs, grip strength and range of motion (ROM) after 2 weeks, 5 weeks, 6 months and 12 months. Methods: We used a prospective cohort study that compared patients with displaced DRFs (n = 50), i.e., >10 degrees of dorsal angulation after two reduction attempts, with patients with minimally or non-displaced DRFs after reduction. Both cohorts received the same treatment of 5 weeks of dorsal plaster casting. Complications and functional outcomes (quick disabilities of the arm, shoulder and hand (QuickDASH), patient-rated wrist/hand evaluation (PRWHE), grip strength and EQ-5D scores) were assessed after 5 weeks, 6 months and 12 months post-injury. The protocol of the VOLCON RCT and present observational study has been published (PMC6599306; clinicaltrials.gov: NCT03716661). Results: One year after 5 weeks of dorsal below-elbow casting of low-energy DRFs in patients ≥ 65 years old, we found a complication rate of 6.3% (3/48) in minimally or non-displaced DRFs and 16.6% (7/42) in displaced DRFs (p = 0.18). However, no statistically significant difference was observed in functional outcomes in terms of QuickDASH, pain, ROM, grip strength or EQ-5D scores. Discussion: In patients above 65 years of age, non-operative treatment, i.e., closed reduction and dorsal casting for 5 weeks, yielded similar complication rates and functional outcomes after 1 year regardless of whether the initial fracture was non-displaced/minimally displaced or still displaced after closed reduction. While the initial closed reduction should still be attempted in order to restore the anatomy, failure to achieve the stipulated radiological criteria may not be as important as we thought in terms of complications and functional outcome. Full article

Background: Cardiac tumors are rare, with a low incidence of between 0.0017 and 0.19%. The majority of cardiac tumors are benign and predominantly occur in females. The aim of our study was to examine how outcomes differ between men and women. Methods: From 2015 to 2022, 80 patients diagnosed with suspected myxoma were operated on. In all patients, preoperative, perioperative, and postoperative data were recorded. Such patients were identified and included in a retrospective analysis focused on gender-related differences. Results: Patients were predominantly female (n = 64; 80%). The mean age was 62.76 ± 13.42 years in female patients and 59.65 ± 15.84 years in male patients (p = 0.438). The body mass index (BMI) was comparable in both groups: between 27.36 ± 6.16 in male and 27.09 ± 5.75 (p = 0.945) in female patients. Logistic EuroSCORE (LogES) (female: 5.89 ± 4.6; male: 3.95 ± 3.06; p = 0.017) and EuroSCORE II (ES II) (female: 2.07 ± 2.1; male: 0.94 ± 0.45; p = 0.043), both scores to predict the mortality in cardiac surgery, were significantly higher in female patients. Two patients died early, within 30 days after surgery: one male and one female patient. Late mortality was defined as the 5-year survival rate, which was 94.8%, and 15-year survival rate, which was 85.3% in our cohort. Causes of death were not related to the primary tumor operation. The follow up showed that satisfaction with surgery and long-term outcome was high. Conclusion: Predominately female patients presented with left atrial tumors over a 17-year period. Relevant gender differences aside from that were not evident. Surgery could be performed with excellent early (within 30 days after surgery) and late results (follow up after discharge). Full article

Purpose: The postoperative use of a rehabilitative knee brace after isolated primary anterior cruciate ligament (ACL) reconstruction (ACLR) using a hamstring tendon (HT) autograft is controversial. A knee brace may provide subjective safety but can cause damage if applied incorrectly. The aim of this study is to evaluate the effect of a knee brace on clinical outcomes following isolated ACLR using HT autograft. Methods: In this prospective randomised trial, 114 adults (32.4 ± 11.5 years, 35.1% women) underwent isolated ACLR using HT autograft after primary ACL rupture. Patients were randomly assigned to wear either a knee brace (n = 58) or no brace (n = 56) for 6 weeks postoperatively. An initial examination was performed preoperatively, and at 6 weeks and 4, 6, and 12 months. The primary endpoint was the subjective International Knee Documentation Committee (IKDC) score to measure participants’ subjective perceptions. Secondary endpoints included objective knee function assessed by IKDC, instrumented knee laxity measurements, isokinetic strength tests of the knee extensors and flexors, Lysholm Knee Score, Tegner Activity Score, Anterior Cruciate Ligament—Return to Sport after Injury Score, and quality of life determined by Short Form-36 (SF36). Results: There were no statistically significant or clinically meaningful differences in IKDC scores between the two study groups (3.29, 95% confidence interval (CI) −1.39 to 7.97, p = 0.03 for evidence of non-inferiority of brace-free compared with brace-based rehabilitation). The difference in Lysholm score was 3.20 (95% CI −2.47 to 8.87); the difference in SF36 physical component score 0.09 (95% CI −1.93 to 3.03). In addition, isokinetic testing did not reveal any clinically relevant differences between the groups (n.s.). Conclusions: Brace-free rehabilitation is non-inferior to a brace-based protocol regarding physical recovery 1 year after isolated ACLR using HT autograft. Consequently, the use of a knee brace might be avoided after such a procedure. Level of Evidence: Level I, therapeutic study. Full article

This rerandomized clinical trial evaluated the influence of soft liners (SL) on biting force, pain perception, and the oral health-related quality of life (OHRQoL) of complete denture wearers. Twenty-eight completely edentulous patients complaining of ill-fitting lower complete dentures were selected to participate in the study from the Dental Hospital, College of Dentistry, Taibah University. All patients received new complete maxillary and mandibular dentures; then they were randomly divided into two groups (14 patients in each group): the acrylic-based SL group, in which the mandibular denture was lined with an acrylic-based soft liner, and the silicone-based SL group, in which the mandibular denture was lined with a silicone-based soft liner. OHRQoL and maximum bite force (MBF) were assessed in this study before denture relining (baseline), then at one month and three months after relining. The finding showed that both treatment modalities significantly improved the OHRQoL of included patients at one-month and three-month periods compared to baseline records (i.e., dentures before relining) with a statistically significant difference (p < 0.05). However, there is no statistical difference between groups at the baseline, one-, and three-month follow-up periods. Regarding maximum biting force, when acrylic-based SL is compared to silicone-based SL, there is no statistical difference between groups at baseline (75 ± 31 and 83 ± 32 N) and one-month follow-up periods (145 ± 53 and 156 ± 49 N); however, after three months of function, the silicone-based group recorded 166 ± 57 N statistically significant high biting force compared to the acrylic-based group that recorded 116 ± 47 N (p < 0.05). Permanent soft denture liners positively affect maximum biting force, pain perception, and OHRQoL more than conventional dentures. After three months, silicone-based SL outperformed acrylic-based soft liners in maximum biting force, which may indicate better long-term results. Full article

(1) Background: Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related mortality worldwide. Up to 50% of patients with CRC develop metastatic CRC (mCRC). Surgical and systemic therapy advances can now offer significant survival advantages. Understanding the evolving treatment options is essential for decreasing mCRC mortality. We aim to summarize current evidence and guidelines regarding the management of mCRC to provide utility when making a treatment plan for the heterogenous spectrum of mCRC. (2) Methods: A comprehensive literature search of PubMed and current guidelines written by major cancer and surgical societies were reviewed. The references of the included studies were screened to identify additional studies that were incorporated as appropriate. (3) Results: The standard of care for mCRC primarily consists of surgical resection and systemic therapy. Complete resection of liver, lung, and peritoneal metastases is associated with better disease control and survival. Systemic therapy now includes chemotherapy, targeted therapy, and immunotherapy options that can be tailored by molecular profiling. Differences between colon and rectal metastasis management exist between major guidelines. (4) Conclusions: With the advances in surgical and systemic therapy, as well as a better understanding of tumor biology and the importance of molecular profiling, more patients can anticipate prolonged survival. We provide a summary of available evidence for the management of mCRC, highlighting the similarities and presenting the difference in available literature. Ultimately, a multidisciplinary evaluation of patients with mCRC is crucial to selecting the appropriate pathway. Full article

Background/Aims: Vascular factors are involved in the development of glaucoma, including diseases such as hypercholesterolemia (HC), systemic arterial hypertension (SAH), and diabetes mellitus (DM). The aim of this study was to determine the effect of glaucoma disease on peripapillary vessel density (sPVD) and macular vessel density (sMVD) on the superficial vascular plexus, controlling differences on comorbidities such as SAH, DM and HC between glaucoma patients and normal subjects. Methods: In this prospective, unicenter, observational cross-sectional study, sPVD and sMVD were measured in 155 glaucoma patients and 162 normal subjects. Differences between normal subjects and glaucoma patients’ groups were analyzed. A linear regression model with 95% confidence and 80% statistical power was performed. Results: Parameters with greater effect on sPVD were glaucoma diagnosis, gender, pseudophakia and DM. Glaucoma patients had a sPVD 1.2% lower than healthy subjects (Beta slope 1.228; 95%CI 0.798–1.659, p < 0.0001). Women presented 1.19% more sPVD than men (Beta slope 1.190; 95%CI 0.750–1.631, p < 0.0001), and phakic patients presented 1.7% more sPVD than men (Beta slope 1.795; 95%CI 1.311–2.280, p < 0.0001). Furthermore, DM patients had 0.9% lower sPVD than non-diabetic patients (Beta slope 0.925; 95%CI 0.293–1.558, p = 0.004). SAH and HC did not affect most of the sPVD parameters. Patients with SAH and HC showed 1.5% lower sMVD in the outer circle than subjects without those comorbidities (Beta slope 1.513; 95%CI 0.216–2.858, p = 0.021 and 1.549; 95%CI 0.240–2.858, p = 0.022 respectively. Conclusions: Glaucoma diagnosis, previous cataract surgery, age and gender seem to have greater influence than the presence of SAH, DM and HC on sPVD and sMVD, particularly sPVD. Full article

Although COVID-19 may cause various and multiorgan diseases, few research studies have examined the postmortem pathological findings of SARS-CoV-2-infected individuals who died. Active autopsy results may be crucial for understanding how COVID-19 infection operates and preventing severe effects. In contrast to younger persons, however, the patient’s age, lifestyle, and concomitant comorbidities might alter the morpho-pathological aspects of the damaged lungs. Through a systematic analysis of the available literature until December 2022, we aimed to provide a thorough picture of the histopathological characteristics of the lungs in patients older than 70 years who died of COVID-19. A thorough search was conducted on three electronic databases (PubMed, Scopus, and Web of Science), including 18 studies and a total of 478 autopsies performed. It was observed that the average age of patients was 75.6 years, of which 65.4% were men. COPD was identified in an average of 16.7% of all patients. Autopsy findings indicated significantly heavier lungs, with an average weight of the right lung of 1103 g, while the left lung mass had an average weight of 848 g. Diffuse alveolar damage was a main finding in 67.2% of all autopsies, while pulmonary edema had a prevalence of between 50% and 70%. Thrombosis was also a significant finding, while some studies described focal and extensive pulmonary infarctions in 72.7% of elderly patients. Pneumonia and bronchopneumonia were observed, with a prevalence ranging from 47.6% to 89.5%. Other important findings described in less detail comprise hyaline membranes, the proliferation of pneumocytes and fibroblasts, extensive suppurative bronchopneumonic infiltrates, intra-alveolar edema, thickened alveolar septa, desquamation of pneumocytes, alveolar infiltrates, multinucleated giant cells, and intranuclear inclusion bodies. These findings should be corroborated with children’s and adults’ autopsies. Postmortem examination as a technique for studying the microscopic and macroscopic features of the lungs might lead to a better knowledge of COVID-19 pathogenesis, diagnosis, and treatment, hence enhancing elderly patient care. Full article

This study evaluated predictors for choroidal neovascularization (CNV) associated with central serous chorioretinopathy (CSCR) based on multimodal imaging. A retrospective multicenter chart review was conducted on 134 eyes of 132 consecutive patients with CSCR. Eyes were classified as per the multimodal imaging-based classification of CSCR at baseline into simple/complex CSCR and primary episode/recurrent/resolved CSCR. Baseline characteristics of CNV and predictors were evaluated with ANOVA. In 134 eyes with CSCR, 32.8% had CNV (n = 44) with 72.7% having complex CSCR (n = 32), 22.7% having simple (n = 10) and 4.5% having atypical (n = 2). Primary CSCR with CNV were older (58 vs. 47, p = 0.00003), with worse visual acuity (0.56 vs. 0.75, p = 0.01) and of longer duration (median 7 vs. 1, p = 0.0002) than those without CNV. Similarly, recurrent CSCR with CNV were older (61 vs. 52, p = 0.004) than those without CNV. Patients with complex CSCR were 2.72 times more likely to have CNV than patients with simple CSCR. In conclusion, CNV associated with CSCR was more likely in complex CSCR and older age of presentation. Both primary and recurrent CSCR are implicated in CNV development. Patients with complex CSCR were 2.72 times more likely to have CNV than patients with simple CSCR. Multimodal imaging-based classification of CSCR supports detailed analysis of associated CNV. Full article

Although obesity is a well-established risk factor of cardiovascular event, the linkage between obesity and sudden cardiac arrest (SCA) is not fully understood. Based on a nationwide health insurance database, this study investigated the impact of body weight status, measured by body-mass index (BMI) and waist circumference, on the SCA risk. A total of 4,234,341 participants who underwent medical check-ups in 2009 were included, and the influence of risk factors (age, sex, social habits, and metabolic disorders) was analyzed. For 33,345,378 person-years follow-up, SCA occurred in 16,352 cases. The BMI resulted in a J-shaped association with SCA risk, in which the obese group (BMI ≥ 30) had a 20.8% increased risk of SCA compared with the normal body weight group (18.5 ≤ BMI < 23.0) (p < 0.001). Waist circumference showed a linear association with the risk of SCA, with a 2.69-fold increased risk of SCA in the highest waist circumference group compared with the lowest waist circumference group (p < 0.001). However, after adjustment of risk factors, neither BMI nor waist circumference was associated with the SCA risk. In conclusion, obesity is not independently associated with SCA risk based on the consideration of various confounders. Rather than confining the findings to obesity itself, comprehensive consideration of metabolic disorders as well as demographics and social habits might provide better understanding and prevention of SCA. Full article

Liver injury occurs frequently as a consequence of SARS-CoV-2 infection. Direct infection of the liver leads to hepatic impairment with elevated transaminases. In addition, severe COVID-19 is characterized by cytokine release syndrome, which may initiate or exacerbate liver injury. In patients with cirrhosis, SARS-CoV-2 infection is associated with acute-on-chronic liver failure. The Middle East and North Africa (MENA) region is one of the world’s regions characterized by a high prevalence of chronic liver diseases. Both parenchymal and vascular types of injury contribute to liver failure in COVID-19, with a myriad of pro-inflammatory cytokines playing a major role in perpetuating liver injury. Additionally, hypoxia and coagulopathy complicate such a condition. This review discusses the risk factors, and the underlying causes of impaired liver functions in COVID-19, with a focus on key players in the pathogenesis of liver injury. It also highlights the histopathological changes encountered in postmortem liver tissues as well as potential predictors and prognostic factors of such injury, in addition to the management strategies to ameliorate liver damage. Full article

Obesity has been associated with increased intraocular pressure (IOP), but the results are inconsistent. Recently, a subgroup of obese individuals with good metabolic profiles were suggested to have better clinical outcomes than normal-weight individuals with metabolic diseases. The relationships between IOP and different combinations of obesity and metabolic health status have not been investigated. Therefore, we investigated the IOP among groups with different combinations of obesity status and metabolic health status. We examined 20,385 adults aged 19 to 85 years at the Health Promotion Center of Seoul St. Mary’s Hospital between May 2015 and April 2016. Individuals were categorized into four groups according to obesity (body mass index (BMI) ≥ 25 kg/m²) and metabolic health status (defined based on prior medical history or abdominal obesity, dyslipidemia, low high-density lipoprotein cholesterol, high blood pressure, or high fasting blood glucose levels upon medical examination). ANOVA and ANCOVA were performed to compare the IOP among the subgroups. The IOP of the metabolically unhealthy obese group (14.38 ± 0.06 mmHg) was the highest, followed by that of the metabolically unhealthy normal-weight group (MUNW, 14.22 ± 0.08 mmHg), then, the metabolically healthy groups (p < 0.001; 13.50 ± 0.05 mmHg and 13.06 ± 0.03 mmHg in the metabolically healthy obese (MHO) and metabolically healthy normal-weight groups, respectively). Subjects who were metabolically unhealthy showed higher IOP compared to their counterparts who were metabolically healthy at all BMI levels, and there was a linear increase in IOP as the number of metabolic disease components increased, but no difference between normal-weight vs. obese individuals. While obesity, metabolic health status, and each component of metabolic disease were associated with higher IOP, those who were MUNW showed higher IOP than those who were MHO, which indicates that metabolic status has a greater impact than obesity on IOP. Full article

Bevacizumab (BEV) is beneficial for ovarian cancer patients, but the real world’s patient settings differ from those in clinical trials. This study tries to illustrate adverse events in the Taiwanese population. Patients with epithelial ovarian cancer treated with BEV at Kaohsiung Chang Gung Memorial Hospital between 2009 and 2019 were retrospectively reviewed. The receiver operating characteristic curve was adopted to identify the cutoff dose and the presence of BEV-related toxicities. A total of 79 patients receiving BEV in neoadjuvant, frontline, or salvage settings were enrolled. The median follow-up time was 36.2 months. Twenty patients (25.3%) had “De novo” hypertension or the worsening of a preexisting one. Twelve patients (15.2%) had “De novo” proteinuria. Five patients (6.3%) had thromboembolic events/hemorrhage. Four patients (5.1%) had gastrointestinal perforation (GIP), and one patient (1.3%) had wound-healing complications. Patients with BEV-related GIP had at least two risk factors for developing GIP, most of which were conservatively managed. This study revealed a compatible but distinct safety profile from those reported in clinical trials. The presence of BEV-related changes in blood pressure showed a dose-dependent trend. Most of the BEV-related toxicities were managed individually. Patients with potential risks for developing BEV-related GIP should use BEV with caution. Full article

Cardiogenic Shock (CS) complicated by in-hospital (IHCA) or out-of-hospital cardiac arrest (OHCA) has a poor outcome. However, studies regarding the prognostic differences between IHCA and OHCA in CS are limited. In this prospective, observational study, consecutive patients with CS were included in a monocentric registry from June 2019 to May 2021. The prognostic impact of IHCA and OHCA on 30-day all-cause mortality was tested within the entire group and in the subgroups of patients with acute myocardial infarction (AMI) and coronary artery disease (CAD). Statistical analyses included univariable t-test, Spearman’s correlation, Kaplan–Meier analyses, as well as uni- and multivariable Cox regression analyses. A total of 151 patients with CS and cardiac arrest were included. IHCA on ICU admission was associated with higher 30-day all-cause mortality compared to OHCA in univariable COX regression and Kaplan–Meier analyses. However, this association was solely driven by patients with AMI (77% vs. 63%; log rank p = 0.023), whereas IHCA was not associated with 30-day all-cause mortality in non-AMI patients (65% vs. 66%; log rank p = 0.780). This finding was confirmed in multivariable COX regression, in which IHCA was solely associated with higher 30-day all-cause mortality in patients with AMI (HR = 2.477; 95% CI 1.258–4.879; p = 0.009), whereas no significant association could be seen in the non-AMI group and in the subgroups of patients with and CAD. CS patients with IHCA showed significantly higher all-cause mortality at 30 days compared to patients with OHCA. This finding was primarily driven by a significant increase in all-cause mortality at 30 days in CS patients with AMI and IHCA, whereas no difference could be seen when differentiated by CAD. Full article

Fabry disease is a rare X-linked disease characterized by deficient expression and activity of alpha-galactosidase A (α-GalA) with consequent lysosomal accumulation of glycosphingolipid in various organs. Currently, enzyme replacement therapy is the cornerstone of the treatment of all Fabry patients, although in the long-term it fails to completely halt the disease’s progression. This suggests on one hand that the adverse outcomes cannot be justified only by the lysosomal accumulation of glycosphingolipids and on the other that additional therapies targeted at specific secondary mechanisms might contribute to halt the progression of cardiac, cerebrovascular, and renal disease that occur in Fabry patients. Several studies reported how secondary biochemical processes beyond Gb3 and lyso-Gb3 accumulation—such as oxidative stress, compromised energy metabolism, altered membrane lipid, disturbed cellular trafficking, and impaired autophagy—might exacerbate Fabry disease adverse outcomes. This review aims to summarize the current knowledge of these pathogenetic intracellular mechanisms in Fabry disease, which might suggest novel additional strategies for its treatment. Full article

Objectives: The aim of this study was to determine the characteristics of hypozincemia in long COVID patients. Methods: This study was a single-center retrospective observational study for outpatients who visited the long COVID clinic established in a university hospital during the period from 15 February 2021 to 28 February 2022. Characteristics of patients with a serum zinc concentration lower than 70 μg/dL (10.7 μmol/L) were compared with characteristics of patients with normozincemia. Results: In a total of 194 patients with long COVID after excluding 32 patients, hypozincemia was detected in 43 patients (22.2%) including 16 male patients (37.2%) and 27 female patients (62.8%). Among various parameters including the background characteristics of the patients and medical histories, the patients with hypozincemia were significantly older than the patients with normozincemia (median age: 50 vs. 39 years). A significant negative correlation was found between serum zinc concentrations and age in male patients (R = −0.39; p < 0.01) but not in female patients. In addition, there was no significant correlation between serum zinc levels and inflammatory markers. General fatigue was the most frequent symptom in both male patients with hypozincemia (9 out of 16: 56.3%) and female patients with hypozincemia (8 out of 27: 29.6%). Patients with severe hypozincemia (serum zinc level lower than 60 μg/dL) had major complaints of dysosmia and dysgeusia, which were more frequent complaints than general fatigue. Conclusions: The most frequent symptom in long COVID patients with hypozincemia was general fatigue. Serum zinc levels should be measured in long COVID patients with general fatigue, particularly in male patients. Full article

Glioblastoma multiforme (GBM) remains one of the tumors with the worst prognosis. In recent years, a better overall survival (OS) has been described in cases subjected to Gross Total Resection (GTR) that were presenting hypermethylation of Methylguanine-DNA methyltransferase (MGMT) promoter. Recently, also the expression of specific miRNAs involved in MGMT silencing has been related to survival. In this study, we evaluate MGMT expression by immunohistochemistry (IHC), MGMT promoter methylation and miRNA expression in 112 GBMs and correlate the data to patients’ clinical outcomes. Statistical analyses demonstrate a significant association between positive MGMT IHC and the expression of miR-181c, miR-195, miR-648 and miR-767.3p between unmethylated cases and the low expression of miR-181d and miR-648 and between methylated cases and the low expression of miR-196b. Addressing the concerns of clinical associations, a better OS has been described in presence of negative MGMT IHC, in methylated patients and in the cases with miR-21, miR-196b overexpression or miR-767.3 downregulation. In addition, a better progression-free survival (PFS) is associated with MGMT methylation and GTR but not with MGMT IHC and miRNA expression. In conclusion, our data reinforce the clinical relevance of miRNA expression as an additional marker to predict efficacy of chemoradiation in GBM. Full article

Ultrasound guided parasternal block is a regional anaesthesia technique targeting the anterior branches of intercostal nerves, which supply the anterior thoracic wall. The aim of this prospective study is to assess the efficacy of parasternal block to manage postoperative analgesia and reduce opioid consumption in patients undergoing cardiac surgery throughout sternotomy. A total of 126 consecutive patients were allocated to two different groups, receiving (Parasternal group) or not (Control group) preoperative ultrasound guided bilateral parasternal block with 20 mL of 0.5% ropivacaine per side. The following data were recorded: postoperative pain expressed by a 0–10 numeric rating scale (NRS), intraoperative fentanyl consumption, postoperative morphine consumption, time to extubation and perioperative pulmonary performance at incentive spirometry. Postoperative NRS was not significantly different between Parasternal and Control groups with a median (IQR) of 2 (0–4.5) vs. 3 (0–6) upon awakening (p = 0.07); 0 (0–3) vs. 2 (0–4) at 6 h (p = 0.46); 0 (0–2) vs. 0 (0–2) at 12 h (p = 0.57). Postoperative morphine consumption was similar among groups. However, intraoperative fentanyl consumption was significantly lower in the Parasternal group [406.3 ± 81.6 mcg vs. 864.3 ± 154.4, (p < 0.001)]. Parasternal group showed shorter times to extubation [(191 ± 58 min vs. 305 ± 72 min, (p)] and better performance at incentive spirometer with a median (IQR) of 2 raised balls (1–2) vs. 1 (1–2) after awakening (p = 0.04). Ultrasound guided parasternal block provided an optimal perioperative analgesia with a significant reduction in intraoperative opioid consumption, time to extubation and a better postoperative performance at spirometry when compared to the Control group. Full article

Background: Vitamin B12 (cobalamin CBL) is a water-soluble vitamin required to form hematopoietic cells (red blood cells, white blood cells, and platelets). It is involved in the process of synthesizing DNA and myelin sheath. Deficiencies of vitamin B12 and/or folate can cause megaloblastic anemia (macrocytic anemia with other features due to impaired cell division). Pancytopenia is a less frequent exordium of severe vitamin B12 deficiency. Vitamin B12 deficiency can also cause neuropsychiatric findings. In addition to correcting the deficiency, an essential aspect of management is determining the underlying cause because the need for additional testing, the duration of therapy, and the route of administration may differ depending on the underlying cause. Methods: Here, we present a series of four patients hospitalized for megaloblastic anemia (MA) in pancytopenia. All patients diagnosed with MA were studied for a clinic-hematological and etiological profile. Results: All the patients presented with pancytopenia and megaloblastic anemia. Vitamin B12 deficiency was documented in 100% of cases. There was no correlation between the severity of anemia and deficiency of the vitamin. Overt clinical neuropathy was present in none of the cases of MA, while subclinical neuropathy was seen in one case. The etiology of vitamin B12 deficiency was pernicious anemia in two cases and low food intake in the remaining cases. Conclusion: This case study emphasizes the role of vitamin B12 deficiency as a leading cause of pancytopenia among adults. Full article

Locally Recurrent Rectal Cancer (LRRC) remains a major clinical concern; it rapidly invades pelvic organs and nerve roots, causing severe symptoms. Curative-intent salvage therapy offers the only potential for cure but it has a higher chance of success when LRRC is diagnosed at an early stage. Imaging diagnosis of LRRC is very challenging due to fibrosis and inflammatory pelvic tissue, which can mislead even the most expert reader. This study exploited a radiomic analysis to enrich, through quantitative features, the characterization of tissue properties, thus favoring an accurate detection of LRRC by Computed Tomography (CT) and ${}^{18}$F-FDG-Positron Emission Tomography/CT (PET/CT). Of 563 eligible patients undergoing radical resection (R0) of primary RC, 57 patients with suspected LRRC were included, 33 of which were histologically confirmed. After manually segmenting suspected LRRC in CT and PET/CT, 144 Radiomic Features (RFs) were generated, and RFs were investigated for univariate significant discriminations (Wilcoxon rank-sum test, p < 0.050) of LRRC from NO LRRC. Five RFs in PET/CT (p < 0.017) and two in CT (p < 0.022) enabled, individually, a clear distinction of the groups, and one RF was shared by PET/CT and CT. As well as confirming the potential role of radiomics to advance LRRC diagnosis, the aforementioned shared RF describes LRRC as tissues having high local inhomogeneity due to the evolving tissue’s properties. Full article

This study aims to present the evolution of our center’s approach to treating primary hyperparathyroidism (PHPT) from diagnosis to intraoperative interventions. We have also evaluated the intraoperative localization benefits of indocyanine green fluorescence angiography. This retrospective single-center study involved 296 patients who underwent parathyroidectomy for PHPT between January 2010 and December 2022. The preoperative diagnostic procedure included neck ultrasonography in all patients, [99mTc]Tc-MIBI scintigraphy in 278 patients, and, in 20 doubtful cases, [18F] fluorocholine positron emission tomography (PET) computed tomography (CT) was performed. Intraoperative PTH was measured in all cases. Indocyanine green has been administered intravenously since 2020 to guide surgical navigation using a fluorescence imaging system. The development of high precision diagnostic tools that can localize an abnormal parathyroid gland in combination with intra-operative PTH assay (ioPTH) enables the surgical treatment of PHPT patients with focused approaches and excellent results that are stackable with bilateral neck exploration (98% of surgical success). Indocyanine green angiography has the potential to assist surgeons in identifying parathyroid glands rapidly and with minimal risk, especially when pre-operative localization has failed. When everything else fails, it is only an experienced surgeon who can resolve the situation. Full article

(1) Background: Many studies have used a well-known social exclusion task, namely Cyberball, to assess the psychophysiological reactions to ostracism in laboratory settings. However, this task has been recently criticized for its lack of realism. Instant messaging communication platforms are currently central communication channels where adolescents conduct their social life. These should be considered when recreating the emotional experiences that fuel the development of negative emotions. To overcome this limitation, a new ostracism task, namely SOLO (Simulated On-Line Ostracism), recreating hostile interactions (i.e., exclusion and rejection) over WhatsApp was developed. The aim of this manuscript is to compare adolescents’ self-reported negative and positive affect, as well as physiological reactivity (i.e., heat rate, HR; heart rate variability, HRV) exhibited during SOLO to Cyberball. (2) Method: A total of 35 participants (Mage = 15.16; SD = 1.48; 24 females) took part in the study. The first group (n = 23; transdiagnostic group), recruited at an inpatient and outpatient unit of a clinic for children and adolescent psychiatry, psychotherapy, and psychosomatic therapy in Baden-Württemberg (Germany), reported clinical diagnoses linked with emotional dysregulation (e.g., self-injury and depression). The second group (n = 12; control group), recruited in the district of Bavaria and Baden-Württemberg, had no pre-existing clinical diagnoses. (3) Results: The transdiagnostic group showed higher HR (b = 4.62, p < 0.05) and lower HRV (b = 10.20, p < 0.01) in SOLO than in Cyberball. They also reported increased negative affect (interaction b = −0.5, p < 0.01) after SOLO but not after Cyberball. In the control group, no differences in either HR (p = 0.34) or HRV (p = 0.08) between tasks were found. In addition, no difference in negative affect after either task (p = 0.83) was found. (4) Conclusion: SOLO could be an ecologically valid alternative to Cyberball when assessing reactions to ostracism in adolescents with emotional dysregulation. Full article

Background: We queried a global database to understand re-intervention rates following urethroplasty with the goal of evaluating whether they align with previously published data. Methods: Using the TriNetX database and Common Procedural Terminology (CPT) and International Classification of Diseases-10 (ICD) codes, we identified adult male patients with urethral stricture disease (ICD N35) who underwent one-stage anterior (CPT 53410) or posterior urethroplasty (CPT 53415), with or without (substitution urethroplasty) a tissue flap (CPT 15740) or buccal graft (CPT 15240 or 15241). We set urethroplasty as the index event and used descriptive statistics to report the incidence of secondary procedures (using CPT codes) within 10 years after the index event. Results: There were 6606 patients who underwent urethroplasty within the last 20 years, with 14.3% of patients undergoing a second procedure after index event. Upon subgroup analysis, reintervention rates were 14.5% for anterior urethroplasty vs. 12.4% of patients with an anterior substitution urethroplasty (RR 1.7, p = 0.09) and 13.3% for posterior urethroplasty vs. 8.2% for patients with a posterior substitution urethroplasty (RR 1.6, p < 0.01). Conclusions: Most patients will not need any form of re-intervention following urethroplasty. These data align with previously described recurrence rates, which may help urologists counsel patients considering urethroplasty. Full article