J. Clin. Med., Volume 13, Issue 10 (May-2 2024) – 289 articles

The human physiological response “to stress” includes all metabolic and hormonal changes produced by a traumatic event at the micro or macro cellular levels. The main goal of the body’s first response to trauma is to keep physiological homeostasis. The perioperative non-specific adaptation response can sometimes be detrimental and can produce systemic inflammatory response syndrome (SIRS), characterized by hypermetabolism and hyper catabolism. We performed a narrative review consisting of a description of the surgical stress response’s categories of changes (neurohormonal and immunological response) followed by reviewing methods found in published studies to modulate the surgical stress response perioperatively. We described various preoperative measures cited in the literature as lowering the burden of surgical trauma. This article revises the anesthetic drugs and techniques that have an impact on the surgical stress response and proven immune-modulatory effects. We also tried to name present knowledge gaps requiring future research. Our review concludes that proper preoperative measures, adequate general anesthetics, multimodal analgesia, early postoperative mobilization, and early enteral nutrition can decrease the stress response to surgery and ease patient recovery. Anesthetics and analgesics used during the perioperative period may modulate the innate and adaptive immune system and inflammatory system, with a consecutive impact on cancer recurrence and long-term outcomes. Full article

Background/Objectives: In recent times, epigenetics alterations in Hidradenitis suppurativa (HS) have been explored and exploited translationally to guide investigation of new therapeutic approaches. On the other hand, long noncoding RNAs (LncRNAs), main regulators of the epigenetic status of the human genome, have been scarcely investigated, notwithstanding their potential relevance in broad pathogenesis comprehension. Here, we aim to explore the methylation pattern of lncRNAs in HS. Methods: In this case-control study, 24 HS patients and age-, sex- and BMI-matched controls were analyzed to characterize the methylome of lncRNA genes in peripheral blood cells. Gene ontology analysis (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, protein–protein interaction (PPI) network, and MCODE analysis were performed. Results: A set of fifteen lncRNA genes exhibited significantly differential methylation patterns, with ten of them showing hypomethylation and five displaying hypermethylation at specific CpG sites. The hypomethylated lncRNA genes were DLEU2, MESTIT1, CASC2, TUG1, KCNQ1DN, PSORS1C3, PCA3, DSCR8, RFPL1S, and PVT1, while the hypermethylated ones were HAR1A, FAM66B, SNHG9, HCG9, and HCP5. These lncRNA genes have been linked to various important biological processes, including cell proliferation, apoptosis, inflammation, chronic inflammatory skin diseases, and wound healing. Their altered methylation status suggests potential roles in regulating these processes, and may contribute to HS pathogenesis and healing mechanisms. Conclusions: This study revealed an interesting dysregulation pattern of definite lncRNAs in the methylome which is linked to both the development of HS and its comorbidities. Epigenetically altered lncRNAs genes could represent useful biomarkers, and could help in guiding innovative treatment strategies. Full article

Background: Pancreatic neuroendocrine tumors (pNETs) represent a rare subset of pancreatic cancer. Functional tumors cause hormonal changes and clinical syndromes, while non-functional ones are often diagnosed late. Surgical management needs multidisciplinary planning, involving enucleation, distal pancreatectomy with or without spleen preservation, central pancreatectomy, pancreaticoduodenectomy or total pancreatectomy. Minimally invasive approaches have increased in the last decade compared to the open technique. The aim of this study was to analyze the current diagnostic and surgical trends for pNETs, to identify better interventions and their outcomes. Methods: The study adhered to the PRISMA guidelines, conducting a systematic review of the literature from May 2008 to March 2022 across multiple databases. Several combinations of keywords were used (“NET”, “pancreatic”, “surgery”, “laparoscopic”, “minimally invasive”, “robotic”, “enucleation”, “parenchyma sparing”) and relevant article references were manually checked. The manuscript quality was evaluated. Results: The study screened 3867 manuscripts and twelve studies were selected, primarily from Italy, the United States, and China. A total of 7767 surgically treated patients were collected from 160 included centers. The mean age was 56.3 y.o. Enucleation (EN) and distal pancreatectomy (DP) were the most commonly performed surgeries and represented 43.4% and 38.6% of the total interventions, respectively. Pancreatic fistulae, postoperative bleeding, re-operation, and follow-up were recorded and analyzed. Conclusions: Enucleation shows better postoperative outcomes and lower mortality rates compared to pancreaticoduodenectomy (PD) or distal pancreatectomy (DP), despite the similar risks of postoperative pancreatic fistulae (POPF). DP is preferred over enucleation for the pancreas body–tail, while laparoscopic enucleation is better for head pNETs. Full article

Background: Benralizumab has been shown to restore good control of severe eosinophilic asthma (SEA). Robust data on benralizumab effectiveness over periods longer than 2 years are scarce. Methods: This retrospective multicentric study was conducted on 108 Italian SEA patients treated with benralizumab for up to 36 months. Partial and complete clinical remission (CR) were assessed. Data were analyzed with descriptive statistics or using linear, logistic, and negative binomial mixed-effect regression models. Results: At 36 months, benralizumab reduced the exacerbation rate by 89% and increased the forced expiratory volume in 1 second (FEV₁) (+440 mL at 36 months, p < 0.0001). Benralizumab improved asthma control as well as sinonasal symptoms in patients with chronic rhinosinusitis with nasal polyposis (CRSwNP). Up to 93.33% of patients either reduced or discontinued OCS; benralizumab also decreased ICS use and other asthma medications. Overall, 84.31% of patients achieved partial or complete CR. Conclusions: Benralizumab improved asthma and sinonasal outcomes up to 36 months. These findings support the potential of benralizumab to induce CR, emphasizing its role as a disease-modifying anti-asthmatic drug for the management of SEA. Further research is warranted to expand these findings by minimizing data loss and assessing benralizumab’s long-term safety. Full article

Background: Graves’ ophthalmopathy (GO) is characterized by upper eyelid retraction (UER), the most prevalent clinical sign. We aimed to assess the clinical efficacy of a multimodal combination of steroids, 5-fluorouracil (5-FU), and botulinum neurotoxin A (BoNT-A) injections in managing UER with GO and analyze the clinical factors in relation to the injection response. Methods: A total of 37 eyes from 23 patients were enrolled for UER with GO. At the endocrinology clinic, the patients were referred to the ophthalmology clinic after taking antithyroid medication for an average of 5.76 months (13 patients), while 10 patients were initially diagnosed with GO and referred to the endocrinology clinic for management of the thyroid hormone function. They performed an orbital computed tomography (CT) scan and measured the cross-sectional area of the orbit, orbital fat, and each extra ocular muscle (EOM) except for the inferior oblique muscle 4 mm behind the eyeball. Each of the EOMs and orbital fat were calculated as a ratio to the total orbit area. A total of 0.1 cc of triamcinolone (40 mg/mL), dexamethasone (5 mg/mL), 5-FU, and BoNT-A (2.5 units) was injected transconjunctivally. Medical records were examined and photographs were utilized to assess MRD1, inferior palpebral fissure (IPF), and lid lag during down gaze before and after the injection. The patients were divided into two groups: responders (more than 1 mm decrease in MRD1 after injection) and non-responders. During the follow-up period (11.0 ± 11.6 months), any potential adverse effects were monitored. Results: CAS decreased from 3.0 ± 0.8 to 1.4 ± 0.5 after the injection, and MRD1 decreased from 5.0 ± 0.9 mm to 4.5 ± 1.3 mm. Sixty percent of the patients were responders. Before and after the injection, the difference between IPF and MRD1 in responders was 0.60 ± 1.10 mm and 0.90 ± 0.90 mm, respectively, whereas, in non-responders, it was −0.57 ± 0.88 mm and −0.15 ± 0.75 mm, respectively. In the responders, pre-injection IPF and FT4 were significantly higher (p < 0.05). Responders had a larger EOM cross-sectional area (153.5 ± 18.0 mm²), including a larger lateral rectus muscle cross-sectional area (37.6 ± 9.7 mm²) than non-responders (132.0 ± 27.9 mm²; 29.1 ± 8.1 mm²). In responders, the treatment effect on IPF and MRD1 remained consistent at 1.2 ± 3.4 mm and 1.2 ± 1.6 mm, respectively, during the latest follow-up assessment. Conclusions: The combination injection of corticosteroids, 5-FU, and BoNT-A would be effective, especially, in patients with hyperthyroidism and an elongated IPF. Additionally, an increase in EOM cross-sectional area on CT, up to 150 mm², may serve as an additional positive indicator for the use of multimodal injections in UER with GO. Full article

Background/Objectives: Presbyopia, a common age-related refractive error, affects over a billion people globally and significantly impacts daily life. Methods: This retrospective study analyzed 288 eyes of 144 patients undergoing LBV PRESBYOND^® treatment for myopic presbyopia with astigmatism, aiming to evaluate precision, efficacy, safety, and stability over six months. Results: Key findings include high efficacy, with 99% of distance-eyes achieving uncorrected distance visual acuity (UDVA) of 20/25 or better, and 85% of near-eyes achieving UDVA of 20/32 or better. The results show excellent refractive outcomes, with 99% of long-sighted eyes and 97% of near-sighted eyes having a postoperative spherical equivalent within ±1.00 D. Safety was demonstrated by no loss of two or more Snellen lines after treatment, with 94% of patients maintaining corrected distance visual acuity (CDVA) before and after surgery. Conclusions: Overall, LBV PRESBYOND^® proved effective, safe, and well tolerated for myopic presbyopia correction, offering satisfactory visual outcomes and potential spectacle independence for various distances. This study underscores the importance of individualized treatment based on patient age, highlighting the positive impact of binocular summation on visual function. This study contributes to the growing body of evidence supporting LBV PRESBYOND^® as a viable option for addressing presbyopic myopia, offering insights into its efficacy and safety profile. Further research could explore postoperative stereopsis and long-term outcomes to enhance understanding and refine treatment protocols. Full article

Background: This systematic review examines the efficacy of multiorgan resection (MOR) in treating locally advanced gastric cancer (LAGC), focusing on survival outcomes, postoperative morbidity, and mortality. Methods: We conducted a comprehensive search of studies in PubMed, Scopus, and Embase up to November 2023, based on the PRISMA guidelines. The inclusion criteria focused on clinical trials, observational studies, case–control studies, and qualitative research, involving patients of any age and gender diagnosed with LAGC undergoing MOR aimed at R0 resection, with secondary outcomes focusing on survival rates, postoperative outcomes, and the effects of adjuvant and neoadjuvant therapies. Exclusion criteria ruled out non-human studies, research not specifically focused on LAGC patients undergoing MOR, and studies lacking clear, quantifiable outcomes. The quality assessment was performed using the Newcastle–Ottawa Scale. The final analysis included twenty studies, involving a total of 2489 patients across a time span from 2001 to 2023. Results highlighted a significant variation in median survival times ranging from 10 to 27 months and R0 resection rates from 32.1% to 94.3%. Survival rates one-year post-R0 resection varied between 46.7% and 84.8%, with an adjusted weighted mean of 66.95%. Key predictors of reduced survival included esophageal invasion and peritoneal dissemination, the presence of more than six lymph nodes, and tumor sizes over 10 cm. Nevertheless, the meta-analysis revealed a significant heterogeneity (I² = 87%), indicating substantial variability across studies, that might be caused by differences in surgical techniques, patient demographics, and treatment settings which influence survival outcomes. Results: The review underlines the important role of achieving R0 resection status in improving survival outcomes, despite the high risks associated with MOR. Variability across studies suggests that local practice patterns and patient demographics significantly influence results. Conclusions: The findings emphasize the need for aggressive surgical strategies to improve survival in LAGC treatment, highlighting the importance of achieving curative resection despite inherent challenges. Full article

Background: Literature is sparse on outcome comparisons between different trochleoplasty techniques in the treatment of patella instability. To date, it is unclear whether there is a technique that offers superior outcomes. This systematic review and meta-analysis aims to compare and evaluate the outcomes of trochleoplasty techniques in the treatment of patellofemoral instability in trochlea dysplasia to establish whether there is an ideal choice of trochleoplasty technique for superior outcomes. Methods: 21 studies involving 880 knees were included. The mean age of the patients was 21.7 years (range 8–49 years). Mean follow-up timeframe of 43.5 months (range 8.8–100 months). Clinical outcomes assessed included rates of recurrence of patellofemoral dislocation, patient satisfaction, Kujala score, International Knee Documentation Committee (IKDC) score, Tegner score, and Lysholm score. Egger’s test showed no publication bias across all outcomes assessed. Results: Favourable results were seen across all outcomes assessed and patient satisfaction. Improvements were seen with Kujala, IKDC, and Lysholm scores. Tegner scores showed good return to function. Post-operative dislocation and complication rates were low across the different techniques. Meta-regression for Kujala and IKDC scores showed good outcomes regardless of trochleoplasty technique used (Kujala, p = 0.549, relative risk 492.06; IKDC, p = 0.193, RR 0.001). The exact risk that trochleoplasty poses to the cartilage remains uncertain, as no study had a conservatively managed arm for comparison. Conclusions: Trochleoplasty yielded good outcomes irrespective of technique used with no clear superiority demonstrated in any technique in terms of outcome scores, satisfaction, post-operative dislocation rates or complications. Full article

This review examines respiratory complications in autoimmune rheumatic diseases within intensive care units (ICUs). The respiratory system, primarily affected in diseases like rheumatoid arthritis, systemic lupus erythematosus, and scleroderma, often leads to respiratory failure. Common manifestations include alveolar hemorrhage, interstitial fibrosis, and acute respiratory distress syndrome. Early recognition and treatment of non-malignant conditions are crucial to prevent rapid disease progression, with ICU mortality rates ranging from 30% to 60%. Delayed immunosuppressive or antimicrobial therapy may result in organ system failure. Collaboration with rheumatic specialists is vital for accurate diagnosis and immediate intervention. Mortality rates for rheumatic diseases in the ICU surpass those of other conditions, underscoring the need for specialized care and proactive management. The review emphasizes comprehensive assessments, distinguishing disease-related complications from underlying issues, and the importance of vigilant monitoring to enhance patient outcomes. Full article

Objectives: The aim of this retrospective study was to evaluate the results of complementary TEVAR following the frozen elephant trunk (FET) procedure for patients with residual type A aortic dissection (rTAAD) in terms of technical feasibility, safety and mid-term outcomes. Methods: This was a retrospective single-centre analysis of patients who received TEVAR after FET for rTAAD from January 2012 up to December 2021. The primary endpoint was technical success. Safety parameters included 30-day/in-hospital morbidity and mortality. Furthermore, mid-term clinical and morphological outcomes were evaluated. Results: Among 587 TEVAR procedures, 60 patients (11 with connective tissue disorders) who received TEVAR after FET for rTAAD were identified. The median interval between FET and TEVAR was 28.5 months. Indications for TEVAR after FET were true lumen collapse distal to FET prosthesis (n = 7), dSINE (n = 2), planned completion (n = 13) and aortic diameter progression (n = 38). In forty-seven patients, TEVAR was performed in an elective setting; eight and six patients were operated on in an urgent or emergency setting, respectively. All TEVAR procedures were successfully completed. The 30-day mortality and spinal cord ischemia rates were 1.7%. During a median follow-up of 37 months, two further patients died. Nine patients had to undergo a further aortic intervention: fenestrated stent-graft (n = 3) or open repair of the infrarenal abdominal aorta (n = 6). Conclusions: Complementary TEVAR following FET for rTAAD showed excellent technical success and low perioperative risk, supporting the feasibility and safety of this strategy. Despite the favourable mid-term survival, certain patients might require a further aortic procedure. Full article

Background: Diabetes mellitus (DM) is a chronic condition associated with multiple complications and comorbidities. Some of these comorbidities are anxiety and depression, with a negative impact on the quality of life, non-adherence to treatment, and poor prognosis. The main aim of this study was to evaluate depression and anxiety in a group of patients with DM and their impact on quality of life and identify factors that improve the prognosis and increase the life expectancy and quality of life of patients with DM. Methods: A total of 209 patients with type 2 DM (T2DM) were enrolled cross-sectionally. Patients were screened for psychiatric disorders, cognitive impairment, and metabolic parameters. Results: Included patients had a median age of 66.0 (58; 70) years, a median DM duration of 9 (6; 15) years, and a suboptimal glycemic control reflected by a median HbA1c of 7.8 (7; 9.2) mg/dL. Patients presented anxiety at different stages in 51.5% of cases, and similarly, depression in 37.5% of cases. Age, duration of DM, HbA1c, and postprandial hyperglycemia (PPG) were predictive factors for anxiety and depression in patients with T2DM. An age > 57 years (sensitivity 84.3, specificity 33.7, AUROC 0.621, p = 0.002) and an HbA1c > 8.5% (sensitivity 45.8, specificity 83.1, AUROC = 0.635, p < 0.0001) predict a higher rate of anxiety, respectively, of depression in these patients. Conclusions: Patients with T2DM have an increased rate of anxiety and depression due to persistent hyperglycemia and aging, which is expressed in a lower quality of life. Full article

Background: Although osteoarthritis (OA) development is epidemiologically multifactorial, a primary underlying mechanism is still under debate. Understanding the pathophysiology of OA remains challenging. Recently, experts have focused on autophagy as a contributor to OA development. Method: To better understand the pathogenesis of OA, we survey the literature on the role of autophagy and the molecular mechanisms of OA development. To identify relevant studies, we used controlled vocabulary and free text keywords to search the MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, Web of Science, and SCOPUS database. Thirty-one studies were included for data extraction and systematic review. Among these studies, twenty-five studies investigated the effects of autophagy in aging and OA chondrocytes, six studies examined the effects of autophagy in normal human chondrocytes, and only one study investigated the effects of mechanical stress-induced autophagy on the development of OA in normal chondrocytes. Results: The studies suggest that autophagy activation prevents OA by exerting cell-protective effects in normal human chondrocytes. However, in aging and osteoarthritis (OA) chondrocytes, the role of autophagy is intricate, as certain studies indicate that stimulating autophagy in these cells can have a cytotoxic effect, while others propose that it may have a protective (cytoprotective) effect against damage or degeneration. Conclusions: Mechanical stress-induced autophagy is also thought to be involved in the development of OA, but further research is required to identify the precise mechanism. Thus, autophagy contributions should be interpreted with caution in aging and the types of OA cartilage. Full article

Background/Objectives: Esophageal achalasia is an archetypal esophageal motility disorder characterized by abnormal peristalsis of the esophageal body and impaired lower esophageal sphincter (LES) relaxation. Methods: In this study, the mRNA expression of docking proteins 1 and 2 (DOK1 and DOK2, respectively) were analyzed and the mechanisms underlying achalasia onset were investigated. Results: DOK1 and DOK2 mRNA levels significantly increased in the LES of patients with achalasia. Moreover, significant correlations were observed between IL-1β and DOK1, IL-1β and DOK2, ATG16L1 and DOK1, and HSV1-miR-H1-3p and DOK2 expression levels. However, a correlation between ATG16L1 and DOK2 or between HSV-miR-H1-3p and DOK1 expression was not observed. In addition, a positive correlation was observed between patient age and DOK1 expression. Microarray analysis revealed a significant decrease in the expression of hsa-miR-377-3p and miR-376a-3p in the LES muscle of patients with achalasia. Conclusions: These miRNAs possessed sequences targeting DOK. The upregulation of DOK1 and DOK2 expression induces IL-1β expression in the LES of achalasia patients, which may contribute to the development of esophageal motility disorder. Full article

Background/Objectives: Proficient colposcopy is crucial for the adequate management of cervical cancer precursor lesions; nonetheless its limitations may impact its cost-effectiveness. The development of artificial intelligence models is experiencing an exponential growth, particularly in image-based specialties. The aim of this study is to develop and validate a Convolutional Neural Network (CNN) for the automatic differentiation of high-grade (HSIL) from low-grade dysplasia (LSIL) in colposcopy. Methods: A unicentric retrospective study was conducted based on 70 colposcopy exams, comprising a total of 22,693 frames. Among these, 8729 were categorized as HSIL based on histopathology. The total dataset was divided into a training (90%, n = 20,423) and a testing set (10%, n = 2270), the latter being used to evaluate the model’s performance. The main outcome measures included sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), and the area under the receiving operating curve (AUC-ROC). Results: The sensitivity was 99.7% and the specificity was 98.6%. The PPV and NPV were 97.8% and 99.8%, respectively. The overall accuracy was 99.0%. The AUC-ROC was 0.98. The CNN processed 112 frames per second. Conclusions: We developed a CNN capable of differentiating cervical cancer precursors in colposcopy frames. The high levels of accuracy for the differentiation of HSIL from LSIL may improve the diagnostic yield of this exam Full article

(1) Background. Digital subtraction angiography (DSA) is indispensable for diagnosing cerebral aneurysms due to its superior imaging precision. However, optimizing X-ray parameters is crucial for accurate diagnosis, with X-ray tube settings significantly influencing image quality. Understanding the relationship between skull dimensions and X-ray parameters is pivotal for tailoring imaging protocols to individual patients. (2) Methods. A retrospective analysis of DSA data from a single center was conducted, involving 251 patients. Cephalometric measurements and statistical analyses were performed to assess correlations between skull dimensions and X-ray tube parameters (voltage and current). (3) Results. The study revealed significant correlations between skull dimensions and X-ray tube parameters, highlighting the importance of considering individual anatomical variations. Gender-based differences in X-ray parameters were observed, emphasizing the need for personalized imaging protocols. (4) Conclusions. Personalized approaches to DSA imaging, integrating individual anatomical variations and gender-specific differences, are essential for optimizing diagnostic outcomes. While this study provides valuable insights, further research across multiple centers and diverse imaging equipment is warranted to validate these findings. Full article

Background/Objectives: Community-acquired pneumonia (CAP) is a common emergency presentation in Australia, with the choice of admitting specialty unit often influenced by pneumonia severity and comorbidities. However, it remains unclear whether there are between-specialty differences in patient characteristics and outcomes. We sought to address this issue by investigating the characteristics and outcomes of CAP patients admitted to General Medicine (GM) versus Respiratory units. Methods: This retrospective observational study utilised data from the two largest metropolitan hospitals in South Australia, encompassing all non-COVID-19-related CAP admissions throughout 2021 to 2023. The hospital length of stay (LOS), in-patient and 30-day mortality, and 30-day readmission rates were assessed by propensity score matching (PSM) using 17 variables. Results: Of the 3004 cases of non-COVID-19 CAP admitted across the two hospitals during the study period, 2673 (71.8%) were admitted under GM units and 331 (9.1%) under Respiratory units. GM patients were, on average, a decade older, presented with a significantly higher burden of comorbidities, exhibited a greater prevalence of frailty, and had higher pneumonia severity compared to those admitted under a Respiratory unit (p < 0.05). Unadjusted analysis revealed a shorter median LOS among GM-admitted patients (5.9 vs. 4.1 days, p < 0.001). After PSM adjustment, patients admitted under the Respiratory units had an 8-fold higher odds of a longer LOS compared to GM (adjusted odds ratio [aOR] 8.53, 95% CI 1.96–37.25, p = 0.004). Other clinical outcomes were comparable between the two groups. Conclusions: Our findings indicate that GM units compared to Respiratory units provide efficient and safe care for patients requiring hospitalisation for CAP. Full article

Objective: This study aimed to compare the incidence rates (IRs) of infections, including herpes zoster (HZ), in rheumatoid arthritis (RA) patients treated with Janus kinase inhibitors (JAKis) or interleukin-6 inhibitors (IL-6is). Methods: We retrospectively analyzed 444 RA patients treated using IL-6is (n = 283) or JAKis (n = 161). After adjusting for clinical characteristic imbalances by propensity score matching (PSM), we compared the IRs of infections including HZ between the JAKi and IL-6i groups. Results: Observational period: 1423.93 patient years (PY); median observational period: 2.51 years. After PSM, incidence rate ratios comparing JAKi with IL-6i were 3.45 (95% confidence interval [CI]: 1.48–9.04) for serious infections other than HZ indicating that the JAKi-treated group was more likely to develop serious infection than the IL-6i-treated group. Multivariate Cox regression analyses revealed that the use of prednisolone > 5.0 mg/day, coexisting interstitial lung disease (ILD), and diabetes mellitus (DM) were independent risk factors for serious infections. The crude IR for HZ was significantly higher in the JAKi group, but the difference between groups was not significant (IRR: 2.83, 95% CI: 0.87–10.96) in PSM analysis. Unadjusted and PSM analyses performed in our study showed increased IRs of serious infections in patients with RA treated with JAKis compared with those treated with IL-6is. Conclusions: The presence of ILD or DM and the use of prednisolone were found to be independent risk factors for serious infection in RA patients treated using JAKis. Whereas the IRs for HZ after PSM were not significantly different between the JAKi and IL-6i groups. Full article

Background: This is a retrospective longitudinal study comparing 374 patients with Parkinson’s disease (PD) who were treated in centers offering a specialized program of enhanced rehabilitation therapy in addition to expert outpatient care to 387 patients with PD, who only received expert outpatient care at movement disorders centers in Italy. Methods: The data are from subjects recruited in the Parkinson’s Outcome Project (POP) at six Italian centers that are part of a multicenter collaboration for care quality improvement (the Fresco Network). The effects were measured with a baseline and a follow-up clinical evaluation of the Timed-Up-and-Go test (TUG), Parkinson’s Disease Questionnaire (PDQ-39), and Multidimensional Caregiver Strain Index (MCSI), the number of falls and hospitalizations for any cause. We used a generalized linear mixed model with the dependent variables being the response variable, which included the covariates demographics, evaluation, and treatment variables. Results: We found that the subjects who underwent specialized enhanced rehabilitation had a better motor outcome over time than those who were managed by expert neurologists but had participated in community programs for exercise and other allied health interventions. The greatest effects were seen in patients in the early stages of the disease with a high amount of vigorous exercise per week in the last six months. Similar effects were seen for PDQ39, MCSI, the number of falls, and hospitalization. Conclusions: Long-term benefits to motor function and the quality of life in patients with PD and burden reduction in their caregivers can be achieved through a systematic program of specialized enhanced rehabilitation interventions. Full article

Introduction: Indonesia, as a developing country, has limited data on the factors associated with 30-day mortality in COVID-19 patients in Indonesia. As a matter of fact, study analyzing factors associated with 30-day mortality of COVID-19 infection in Indonesia has never been conducted. This study aims to fill this gap in the literature by conducting a large-scale analysis of factors associated with 30-day mortality in COVID-19 patients in Indonesia. Method: This study employed a single-center retrospective cohort observational design, and was conducted at Cipto Mangunkusumo National General Hospital between the years 2022 and 2023. Sampling was conducted using the consecutive sampling method. The study included patients aged 18 years and above who had been confirmed to have COVID-19 infection. Survival analysis was conducted using Kaplan–Meier and multivariate Cox regression analysis. Result: Our study included a total of 644 patients, with 120 patients (18.6%) expiring within 30 days. In the multivariate analysis using the backward Wald method, severe COVID-19 (HR: 7.024; 95% CI: 3.971–12.744; p value: <0.0001), moderate COVID-19 infection (HR: 1.660; 95% CI: 1.048–2.629; p value: 0.031), liver cirrhosis (HR: 3.422; 95% CI: 1.208–9.691; p value: 0.021), female sex (HR: 1.738; 95% CI: 1.187–2.545; p value: 0.004), old age (HR: 2.139; 95% CI: 1.279–3.577; p value: 0.004), high leukocyte (HR: 11.502; 95% CI: 1.523–86.874; p value: 0.018), high NLR (HR: 1.720; 95% CI: 1.049–2.819; p value: 0.032), high CRP (HR: 1.906; 95% CI: 1.092–3.329; p value: 0.023), high procalcitonin (HR: 3.281; 95% CI: 1.780–6.049; p value: 0.001), and high creatinine (HR: 1.863; 95% CI: 1.240–2.800; p value: 0.003) were associated with 30-day mortality from COVID-19 infection. Subgroup analysis excluding cancer patients showed that age, D-Dimer, CRP, and PCT were associated with 30-day mortality in COVID-19 patients, while steroid therapy is protective. Conclusions: This study finds that COVID-19 severity, liver cirrhosis, sex, age, leukocyte, NLR, CRP, creatinine, and procalcitonin were associated with COVID-19 mortality within 30 days. These findings underscore the multifactorial nature of COVID-19 infection mortality. It is important, therefore, that patients which exhibit these factors should be treated more aggressively to prevent mortality. Full article

Transcatheter aortic valve implantation (TAVI) has revolutionised the management of aortic valve disease, offering a less invasive alternative to traditional surgical valve replacement for severe aortic stenosis (AS). TAVI for pure aortic regurgitation (AR) is less well established, and, in fact, it was previously labelled as a relative contraindication. However, TAVI has been utilised for selected cases of pure or predominant AR. The primary limitations regarding the use of TAVI in AR are related to the absence of anatomical factors seen in patients with AS that have contributed to the safe and stable functioning of current-generation prostheses. These include aortic root dilatation, mobile valve leaflets and labile blood pressure within the aortic root, which may further increase the risk of valve migration and periprosthetic leak after deployment. Furthermore, patients with AR have more heterogeneous aortic root anatomies when compared to the population of patients with calcific or degenerative AS. This review article describes the current evidence for the off-label use of TAVI in pure AR and the various clinical syndromes associated with AR where there may be specific challenges in the application of TAVI. Full article

Improvements in medical technology have significantly changed the management of congenital heart disease (CHD), offering novel tools to predict outcomes and personalize follow-up care. By using sophisticated imaging modalities, computational models and machine learning algorithms, clinicians can experiment with unprecedented insights into the complex anatomy and physiology of CHD. These tools enable early identification of high-risk patients, thus allowing timely, tailored interventions and improved outcomes. Additionally, the integration of genetic testing offers valuable prognostic information, helping in risk stratification and treatment optimisation. The birth of telemedicine platforms and remote monitoring devices facilitates customised follow-up care, enhancing patient engagement and reducing healthcare disparities. Taking into consideration challenges and ethical issues, clinicians can make the most of the full potential of artificial intelligence (AI) to further refine prognostic models, personalize care and improve long-term outcomes for patients with CHD. This narrative review aims to provide a comprehensive illustration of how AI has been implemented as a new technological method for enhancing the management of CHD. Full article

Background: People with spinal cord injuries (SCIs) often have trouble remaining active because of paralysis. In the past, exercise recommendations focused on the non-paralyzed muscles in the arms, which provides limited benefits. However, recent studies show that electrical stimulation can help engage the paralyzed extremities, expanding the available muscle mass for exercise. Methods: The authors provide an evidence-based approach using expertise from diverse fields, supplemented by evidence from key studies toward the management of electrical stimulation therapies in individuals with SCIs. Literature searches were performed separately using the PubMed, Medline, and Google Scholar search engines. The keywords used for the searches included functional electrical stimulation cycling, hybrid cycling, neuromuscular electrical stimulation exercise, spinal cord injury, cardiovascular health, metabolic health, muscle strength, muscle mass, bone mass, upper limb treatment, diagnostic and prognostic use of functional electrical stimulation, tetraplegic hands, and hand deformities after SCI. The authors recently presented this information in a workshop at a major rehabilitation conference. Additional information beyond what was presented at the workshop was added for the writing of this paper. Results: Functional electrical stimulation (FES) cycling can improve aerobic fitness and reduce the risk of cardiovascular and metabolic diseases. The evidence indicates that while both FES leg cycling and neuromuscular electrical stimulation (NMES) resistance training can increase muscle strength and mass, NMES resistance training has been shown to be more effective for producing muscle hypertrophy in individual muscle groups. The response to the electrical stimulation of muscles can also help in the diagnosis and prognosis of hand dysfunction after tetraplegia. Conclusions: Electrical stimulation activities are safe and effective methods for exercise and testing for motor neuron lesions in individuals with SCIs and other paralytic or paretic conditions. They should be considered part of a comprehensive rehabilitation program in diagnosing, prognosing, and treating individuals with SCIs to improve function, physical activity, and overall health. Full article

Objectives: Although acute anterior cruciate ligament reconstruction (ACLR) is often avoided because of postoperative joint stiffness, delayed ACLR can lead to a longer recovery time and can have a negative impact on physical function due to detraining. This study aimed to determine the effects of acute ACLR on postoperative outcomes, including muscle strength, performance, and return to sports. Methods: A total of 110 patients who underwent anatomical ACLR using hamstring autografts were included in this study and were divided into three groups: acute (ACLR performed within 2 weeks after ACL injury), 2–6 weeks (ACLR performed between 2 and 6 weeks after injury), and 6–12 weeks (ACLR performed between 6 and 12 weeks after injury). Several parameters were evaluated, including range of motion, knee joint stability, isokinetic knee strength, performance, and return to sports. Results: No significant differences were found in the range of motion or knee joint stability between the groups. The acute group exhibited significantly greater quadriceps strength at 3 months postoperatively than the other groups (p < 0.05). The single-leg hop test showed that 66.7%, 38.7%, and 33.3% of the patients in the acute, 2–6 weeks, and 6–12 weeks groups, respectively, recovered to an LSI of 90% or greater (p = 0.09, Cramer’s V = 0.27). All patients in the acute group were able to return to sports (p = 0.14; Cramer’s V = 0.28). Conclusions: Acute ACLR is advantageous for the early recovery of strength and performance without adverse events. Acute ACLR may shorten the time spent away from sports activities. Full article

Type 3c diabetes mellitus (T3cDM), also known as pancreatogenic or pancreoprivic diabetes, is a specific type of DM that often develops as a result of diseases affecting the exocrine pancreas, exhibiting an array of hormonal and metabolic characteristics. Several pancreatic exocrine diseases and surgical procedures may cause T3cDM. Diagnosing T3cDM remains difficult as the disease characteristics frequently overlap with clinical presentations of type 1 DM (T1DM) or type 2 DM (T2DM). Managing T3cDM is likewise challenging due to numerous confounding metabolic dysfunctions, including pancreatic endocrine and exocrine insufficiencies and poor nutritional status. Treatment of pancreatic exocrine insufficiency is of paramount importance when managing patients with T3cDM. This review aims to consolidate the latest information on surgical etiologies of T3cDM, focusing on partial pancreatic resections, total pancreatectomy, pancreatic cancer and trauma. Full article

(1) Background. Coeliac disease (CD) often co-occurs with autoimmune conditions or genetic syndromes, but there are few studies on the co-existence of CD and immunoglobulin E (IgE)-mediated allergies. The purpose of this study was to assess sensitization to food and aero-allergens in pediatric patients with CD. (2) Methods. A multiplex ALEX^®2 test was used to determine specific IgEs (sIgEs). (3) Results. The study included 108 children newly diagnosed with CD. Allergen extract- and/or allergen molecule-sIgEs were detected in 49.1% of children. Most children (41.5%) were sensitized to both inhalant and food allergens. The three most common aero-allergens (timothy pollen, ryegrass, silver birch) were molecules Phl p 1, Lol p 1, and Bet v 1. The most common food allergens (hazelnut, apple, and peanut) were Cor a 1, Mal d 1, and Ara h 8 molecules of the PR-10 subfamily. Patients were not sensitized to cereal allergens containing gluten. Spearman’s rank correlation analysis of sensitized patients showed a significant positive relationship (r = 0.31) between the patients’ age and the occurrence of positive sIgEs (≥0.3 kU_A/L) for inhalant allergen molecules (p = 0.045). In sensitized patients, mainly symptoms of inhalant allergy were observed, such as hay fever, conjunctivitis, and bronchial asthma. (4) Conclusions. The current study indicates the co-occurrence of IgE sensitization to food and inhalant allergens in children with CD. The study highlights the need to take a closer look at the diagnosis of IgE-mediated allergy in patients with CD, which may help in their care and lead to a better understanding of the relationship between CD and IgE-mediated allergy. Full article

Takotsubo syndrome (TTS) is a type of cardiomyopathy usually precipitated by either emotional or physical stress and potentially leading to reversible heart failure. There is emerging evidence indicating an interaction between the brain and the heart in patients with TTS. Nevertheless, these new insights are not reflected in the current clinical approach to TTS. The application of novel and existing imaging modalities for the evaluation of brain–heart interactions is an interesting approach that could potentially augment diagnostic and prognostic yield, as well as improve our pathophysiologic understanding in the context of TTS. In this opinion piece, we discuss the evidence supporting a brain–heart interaction in patients with TTS and discuss how a combined evaluation of brain–heart interactions could potentially be implemented. Full article

The aim of the present study is to explore differences in personality traits and emotion regulation of people suffering from GD, substance-dependent gamblers (SDGs), and healthy controls (HCs). Additionally, the study proposes a new experimental task: the “Gambling Affective Task” (GAT) to investigate the influence of affective priming on risk-taking behaviors. Results: Our findings indicate that participants placed lower bets following positive priming. Additionally, SDGs wagered significantly higher amounts than HCs, regardless of priming type. In general, participants exhibited longer response times after positive priming trials, compared to negative and neutral priming trials. These findings suggest that experiencing positive emotions can act as a protective factor by delaying and lengthening gambling behaviors. By comparing gamblers with and without substance comorbidity, we can gain insight into the exclusive factors of GD and improve our understanding of this disorder. Conclusions: By elucidating the impact of emotional states on risk-taking, the research also provides new insights into the prevention and treatment of GD. Full article

Background: DaVinci^® single-port (SP) robotic surgery offers several benefits compared to traditional multiport laparoscopic or robotic surgeries. One of the main advantages is that it allows for a minimally invasive approach, resulting in a single, smaller incision and reduced trauma to the patient’s body, leading to less postoperative pain, faster recovery, and reduced risk of complications. The cosmesis of a single port with minimal visible scarring is also an attractive aspect to the patients; however, many surgeons use an additional port for energy device, stapler use, and drain insertion. Pure single-port surgery with one incision is still rare. Here, we share our experience of our first 10 cases using the SP robotic platform in colorectal surgery. Methods: From May 2023 to December 2023, colorectal patients who underwent SP robotic surgery were analyzed. Placement of the incision was the umbilicus for eight patients, and right lower quadrant for two patients, through which ileostomy maturation was performed. Data on perioperative parameters and postoperative outcomes were analyzed, with a median follow-up of 4.6 months (range 0.6–7.4 months). Results: A total of 10 colorectal patients underwent DaVinci^® single-port robotic colorectal surgery at our institution during this period. The patient demographic was four males (40%) and six females (60%) with a median age of 63.5 years (range 50–75 years). Median body mass index (BMI) was 22.89 kg/m² (range 19.92–26.84 kg/m²). Nine patients were diagnosed with colorectal cancer, and one patient was diagnosed with a rectal gastrointestinal tumor. One patient underwent anterior resection and cholecystectomy simultaneously. Mean operation time was 222 min (range 142–316 min), and mean wound size was 3.25 cm (range 2.5–4.5 cm). Nine patients underwent surgery with single incision through which a single-port trocar was inserted, and one patient had one additional port for drain insertion. Mean hospital stay was 6 days (range 4–8 days) with one postoperative complication of bleeding requiring transfusion, but there was no readmission within 30 days. Conclusions: Overall, our experience with single-port robotic colorectal surgery has been promising. With only one patient with additional port for drain insertion, all nine patients underwent SP-robotic surgery with single incision for colon as well as rectal surgeries. Compared to an average postoperative length of stay of 6.5-8 days in laparoscopic colorectal surgeries reported in literature, SP-robotic surgery 33showed faster recovery of 6 days highlighting its benefits in patient recovery and satisfaction. Full article

Complex urogenital malformations are clinically highly relevant; thus, they must be appropriately diagnosed and classified before initiating treatment. Background/Objectives: This study aimed to evaluate the applicability and suitability of the embryological–clinical classification of female genital malformations. Methods: A systematic review of cases of genital malformations reported in the literature from 2000 to 2020 was conducted. Case reports and series with the following combinations: “female genital tract” AND (malformation OR anomaly OR müllerian anomaly OR uterine anomaly OR cervical anomaly OR vaginal anomaly OR cloacal anomaly OR urogenital sinus); and “female genital tract” AND (renal agenesis OR ectopic ureter) were searched. A total of 3124 articles were identified, of which 824 cases of genital malformation were extracted. The characteristics of each malformation were included in a database for further analyses. Results: Using the embryological–clinical classification, 89.9% of the published cases and 86.5% of the 52 cases defined as unclassifiable by their authors have been classified in this review. In 73 cases (72.2%), the classification of the malformation using the AFS system was incomplete because although the type of uterine anomaly of the AFS classification matched that of the embryological–clinical classification, characteristics of the urinary system or the vagina were overlooked when using the AFS system. Following a dispersion matrix, we have been able to show that the embryological–clinical classification system is able to classify and subclassify the genitourinary malformations more accurately. Conclusions: The applicability of the embryological–clinical classification has been confirmed after classifying most of the cases of genital malformation previously published. This system also provides a more complete and accurate classification than other classifying systems exclusively based on Müllerian duct development or uterovaginal parameters, demonstrating its suitability. Full article