Medicina, Volume 59, Issue 12 (December 2023) – 151 articles

Context: Several recent randomized controlled trials (RCTs) have reported on the survival benefits of poly (ADP-ribose) polymerase inhibitors (PARPi) compared to standard-of-care (SOC) treatment (enzalutamide, abiraterone, or docetaxel) in patients with metastatic castration-resistant prostate cancer (mCRPC). However, there is a limited integrated analysis of high-quality evidence comparing the efficacy and safety of PARPi and SOC treatments in this context. Objective: This study aims to comprehensively analyze the survival benefits and adverse events associated with PARPi and SOC treatments through a head-to-head meta-analysis in mCRPC. Evidence acquisition: A systematic review search was conducted in PubMed, Embase, Clinical trials, and the Central Cochrane Registry in July 2023. RCTs were assessed following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. The systematic review was prospectively registered on PROSPERO (CRD42023441034). Evidence synthesis: A total of 8 studies, encompassing 2341 cases in the PARPi treatment arm and 1810 cases in the controlled arm, were included in the qualitative synthesis. The hazard ratio (HR) for radiographic progression-free survival (rPFS) and overall survival (OS) were 0.74 (95% CI, 0.61–0.90) and 0.89 (95% CI, 0.80–0.99), respectively, in the intention-to-treatment patients. For subgroup analysis, HRs for rPFS and OS in the BRCA-mutated subgroup were 0.39 (95% CI, 0.28–0.55) and 0.62 (95% CI, 0.38–0.99), while in the HRR-mutated subgroup, HR for rPFS was 0.57 (95% CI, 0.48–0.69) and for OS was 0.77 (95% CI, 0.64–0.93). The odds ratio (OR) for all grades of adverse events (AEs) and AEs with severity of at least grade 3 were 3.86 (95% CI, 2.53–5.90) and 2.30 (95% CI, 1.63–3.26), respectively. Conclusions: PARP inhibitors demonstrate greater effectiveness than SOC treatments in HRR/BRCA-positive patients with mCRPC. Further research is required to explore ways to reduce adverse event rates and investigate the efficacy of HRR/BRCA-negative patients. Full article

Background and Objectives: In the Western world, back pain and sciatica are among the main causes of disability and absence from work with significant personal, social, and economic costs. This prospective observational study aims to evaluate the effectiveness of a rehabilitation program combined with the administration of Alpha Lipoic Acid, Acetyl-L-Carnitine, Resveratrol, and Cholecalciferol in the treatment of sciatica due to herniated discs in young patients in terms of pain resolution, postural alterations, taking painkillers, and quality of life. Materials and Methods: A prospective observational study was conducted on 128 patients with sciatica. We divided the sample into 3 groups: the Combo group, which received a combination of rehabilitation protocol and daily therapy with 600 mg Alpha Lipoic Acid, 1000 mg Acetyl-L-Carnitine, 50 mg Resveratrol, and 800 UI Cholecalciferol for 30 days; the Reha group, which received only a rehabilitation protocol; and the Supplement group, which received only oral supplementation with 600 mg Alpha Lipoic Acid, 1000 mg Acetyl-L-Carnitine, 50 mg Resveratrol, and 800 UI Cholecalciferol. Clinical assessments were made at the time of recruitment (T0), 30 days after the start of treatment (T1), and 60 days after the end of treatment (T2). The rating scales were as follows: the Numeric Rating Scale (NRS); the Oswestry Disability Questionnaire (ODQ); and the 36-item Short Form Health Survey (SF-36). All patients also underwent an instrumental stabilometric evaluation. Results: At T1, the Combo group showed statistically superior results compared to the other groups for pain (p < 0.05), disability (p < 0.05), and quality of life (p < 0.05). At T2, the Combo group showed statistically superior results compared to the other groups only for pain (p < 0.05) and quality of life (p < 0.05). From the analysis of the stabilometric evaluation data, we only observed a statistically significant improvement at T2 in the Combo group for the average X (p < 0.05) compared to the other groups. Conclusions: The combined treatment of rehabilitation and supplements with anti-inflammatory, pain-relieving, and antioxidant action is effective in the treatment of sciatica and can be useful in improving postural stability. Full article

Background and Objectives: Pain management poses a significant challenge for patients experiencing vaso-occlusive crisis (VOC) in sickle cell disease (SCD). While opioid therapy is highly effective, its efficacy can be impeded by undesirable side effects. Local regional anesthesia (LRA), involving the deposition of a perineural anesthetic, provides a nociceptive blockade, local vasodilation and reduces the inflammatory response. However, the effectiveness of this therapeutic approach for VOC in SCD patients has been rarely reported up to now. The objective of this study was to assess the effectiveness of a single-shot local regional anesthesia (LRA) in reducing pain and consequently enhancing the management of severe vaso-occlusive crisis (VOC) in adults with sickle cell disease (SCD) unresponsive to conventional analgesic therapy. Materials and Methods: We first collected consecutive episodes of VOC in critical care (ICU and emergency room) for six months in 2022 in a French University hospital with a large population of sickle cell patients in the West Indies population. We also performed a systematic review of the use of LRA in SCD. The primary outcome was defined using a numeric pain score (NPS) and/or percentage of change in opioid use. Results: We enrolled nine SCD adults (28 years old, 4 females) for ten episodes of VOC in whom LRA was used for pain management. Opioid reduction within the first 24 h post block was −75% (50 to 96%). Similarly, the NPS decreased from 9/10 pre-block to 0–1/10 post-block. Five studies, including one case series with three patients and four case reports, employed peripheral nerve blocks for regional anesthesia. In general, local regional anesthesia (LRA) exhibited a reduction in pain and symptoms, along with a decrease in opioid consumption post-procedure. Conclusions: LRA improves pain scores, reduces opioid consumption in SCD patients with refractory pain, and may mitigate opioid-related side effects while facilitating the transition to oral analgesics. Furthermore, LRA is a safe and effective procedure. Full article

Background and objectives: There are concerns with the current prescribing practices of antibiotics in ambulatory care in Tanzania, including both the public and private sectors. These concerns need to be addressed as part of the national action plan (NAP) of Tanzania to reduce rising antimicrobial resistance (AMR) rates. Issues and concerns include high rates of prescribing of antibiotics for essentially self-limiting conditions. Consequently, there is a need to address this. As a result, the aims of this narrative review were to comprehensively summarize antibiotic utilization patterns particularly in ambulatory care and their rationale in Tanzania and to suggest ways forward to improve future prescribing practices. Materials and Methods: We undertook a narrative review of recently published studies and subsequently documented potential activities to improve future prescribing practices. Potential activities included instigating quality indicators and antimicrobial stewardship programs (ASPs). Results: Published studies have shown that antibiotics are being excessively prescribed in ambulatory care in Tanzania, in up to 95% to 96.3% of presenting cases depending on the sector. This is despite concerns with their appropriateness. High rates of antibiotic prescribing are not helped by variable adherence to current treatment guidelines. There have also been concerns with extensive prescribing of ‘Watch’ antibiotics in the private sector. Overall, the majority of antibiotics prescribed across the sectors, albeit inappropriately, were typically from the ‘Access’ group of antibiotics in the AWaRe (Access/Watch/Reserve) classification rather than ‘Watch’ antibiotics to limit AMR. The inappropriate prescribing of antibiotics in ambulatory care is linked to current knowledge regarding antibiotics, AMR, and ASPs among both prescribers and patients. Recommended activities for the future include improved education for all groups, the instigation of updated quality indicators, and the regular monitoring of prescribing practices against agreed-upon guidelines and indicators. Education for healthcare professionals on ASPs should start at undergraduate level and continue post qualification. Community advocacy on the rational use of antibiotics should also include social media activities to dispel misinformation. Conclusion: The quality of current prescribing practices of antibiotics in ambulatory care is sub-optimal in Tanzania. This needs to be urgently addressed. Full article

Background and Objectives: Rectal cancer poses significant treatment challenges, especially in advanced stages. Radiologic assessment, particularly with MRI, is critical for surgeons and oncologists to understand tumor dynamics and tailor treatment strategies to improve patient outcomes. The purpose of this study was to correlate MRI-based tumor volumetric and tumor regression grade analysis in patients with advanced rectal cancer, assessing the impact of preoperative chemotherapy (CT) alone or chemoradiotherapy (CRT) on surgical technique choices. Materials and Methods: Between 2015 and 2022, a prospective study was enrolled, including a cohort of 89 patients diagnosed with rectal cancer at stage II or III. The participants were divided into two distinct therapy groups, ensuring an equal distribution with a ratio of 1:1. The initial group was treated with the contemporary preoperative chemotherapy protocol FOLFOX4. In contrast, the alternative group received conventional preoperative chemoradiotherapy. Before surgery, each patient underwent a rectal MRI scan at 1.5 T, including T2-weighted and diffusion-weighted imaging (DWI) sequences. Results: The CT group showed a 36.52% tumor volume reduction rate (TVRR), and the CRT group showed 54.87%, with varying magnetic resonance and pathological tumor regression grades (mrTRG and pTRG). Analysis revealed a significant interaction between mrTRG and tumor volumetrics (volume and VRR) in both groups, especially CRT, underscoring the complexity of tumor response. Both treatment groups had similar initial tumor volumes, with CRT displaying a higher TVRR, particularly in higher pathological TRG (3/4) cases. This interaction and the strong correlation between mrTRG and pTRG suggest mrTRG’s role as a non-invasive predictor for treatment response, highlighting the need for personalized treatment plans. Conclusions: Rectal tumor volume, volume reduction rate, and mrTRG are not just abstract measures; they are concrete indicators that have a direct and practical impact on surgical decision-making, planning, and prognosis, ultimately influencing the quality of care and life expectancy of patients with rectal cancer. Full article

Background and Objectives: The acute effects of exercise on the myosin heavy-chain (MHC) isoform mRNA expression and the upstream transcription factors in diabetic and non-diabetic hearts remain unexplored. We aimed to determine the acute effect of a single exercise session on the expression of left ventricular MHC, MHC-α and MHC-β, and thyroid receptor (TR), TR-α1 and TR-β, isoform mRNA in diabetic and non-diabetic rats. Materials and Methods: Sprague-Dawley rats were assigned to four groups: non-diabetic control (CS), diabetic exercise (DIEX), sedentary diabetic (DIS), and non-diabetic exercise (CEX). Diabetes was induced via streptozotocin injection (55 mg/kg). DIEX and CEX rats performed an exercise session (60 min at 50 m/min and 0% grade) 6–7 weeks after diabetes induction. Results: MHC-α mRNA was lower in DIS (p = 0.03) and not different in DIEX (p = 0.1) relative to CS. DIS showed higher MHC-β mRNA than the non-diabetic rats, CS and CEX (p = 0.02 and p = 0.009, respectively). MHC-β mRNA in DIEX was normalized to non-diabetic levels in CS (p = 0.3). TR-α1 was higher in DIS and not different in DIEX relative to CS and CEX (p = 0.03 and p = 1.0, respectively). In CEX, exercise did not change MHC-α, MHC-β, and TR-α1 relative to CS (p = 1.0). TR-β was not different between groups. Conclusion: In conclusion, exercise appears to acutely normalize the myocardial MHC and TR isoform mRNA expression only in the diabetic heart. These responses may induce therapeutic mechanisms other than changing the MHC isoform composition. Full article

Background and Objectives: In case of the ineffectiveness of pharmacological and non-pharmacological treatments in managing chronic neuropathic pain, spinal cord stimulation (SCS) with BurstDR™ stimulation may reduce pain and increase the quality of life. The term “burst” refers to a series of stimulation impulses that are compressed into small packets and separated by intervals of latency. Materials and Methods: A group of 30 consecutive patients who received the BurstDR™ stimulator using the minimally invasive percutaneous method was selected. Patients selected for our study underwent numerous spinal surgeries before SCS implantation. In the study, analgesics and co-analgesics and their doses used by patients before and 6 months after SCS implantation were examined and compared. Using the visual analogue scale (VAS), pain was compared before and after the procedure. Patients` quality of life was assessed using the Oswestry Disability Index (ODI). Results: We observed a significant reduction in opioid daily doses by an average of 32.4% (±36.1%) and a reduction in paracetamol daily doses by an average of 40% (±33.4%). There was a reduction in pregabalin doses as well. Ketoprofen daily dose reduction was 85.4 mg. The mean VAS difference before and after procedure was 3.9 (±2.3), and the mean difference in ODI was 12.9 (±9), which benefits operative treatment. The VAS and ODI results were statistically significant as well. Conclusions: According to our research, BurstDR™ stimulation improves the quality of life by reducing doses of analgesics and the level of pain. Full article

Hepatocellular carcinoma (HCC) still lacks valuable diagnostic and prognostic tools. This study aimed to investigate the potential diagnostic and prognostic value of baseline interleukin (IL)-10, fatty acid-binding protein 2 (FABP2) and lipopolysaccharide (LPS) levels in patients with HCC. Serum levels of IL-10, FABP2 and LPS in 47 newly diagnosed HCC patients and 50 healthy individuals were estimated and compared. The best cut-off points for baseline IL-10, FABP2 and LPS levels predicting overall survival (OS) were evaluated. Both levels of FABP2 and IL-10 were significantly higher in HCC patients vs. control group (median 2095 vs. 1772 pg/mL, p = 0.026; 9.94 vs. 4.89 pg/mL, p < 0.001) and may serve as potential biomarkers in complex HCC diagnostic tools. The cut-off value of 2479 pg/mL for FABP2 was determined to have the highest sensitivity (66.7%) and specificity (55.6%) to distinguish patients with a median OS longer than 17 months. However, the median OS of patients with high and low levels of FABP2 were not significantly different (p = 0.896). The prognostic value of LPS as well as FABP2 and IL-10 for HCC patients appears to be limited. Full article

Phosphodiesterase type 5 (PDE5) is pivotal in cellular signalling, regulating cyclic guanosine monophosphate (cGMP) levels crucial for smooth muscle relaxation and vasodilation. By targeting cGMP for degradation, PDE5 inhibits sustained vasodilation. PDE5 operates in diverse anatomical regions, with its upregulation linked to various pathologies, including cancer and neurodegenerative diseases. Sildenafil, a selective PDE5 inhibitor, is prescribed for erectile dysfunction and pulmonary arterial hypertension. However, considering the extensive roles of PDE5, sildenafil might be useful in other pathologies. This review aims to comprehensively explore sildenafil’s therapeutic potential across medicine, addressing a gap in the current literature. Recognising sildenafil’s broader potential may unveil new treatment avenues, optimising existing approaches and broadening its clinical application. Full article

Background and Objectives: The present study aims to investigate the association between gut microbiota’s oxalate-degrading activity (ODA) and the risk of developing cardiovascular disease (CVD) over a three-year follow-up period in a cohort of patients undergoing kidney replacement therapy (KRT). Additionally, various factors were examined to gain insight into the potential mechanisms underlying the ODA–CVD link. Materials and Methods: A cohort of 32 KRT patients and 18 healthy volunteers was enrolled in this prospective observational pilot study. Total fecal ODA, routine clinical data, plasma oxalic acid (POx), serum indoxyl sulfate, lipid profile, oxidative stress, and proinflammatory markers were measured, and the patients were followed up for three years to assess CVD events. Results: The results revealed that patients with kidney failure exhibited significantly lower total fecal ODA levels compared to the healthy control group (p = 0.017), with a higher proportion showing negative ODA status (≤−1% per 0.01 g) (p = 0.01). Negative total fecal ODA status was associated with a significantly higher risk of CVD events during the three-year follow-up period (HR = 4.1, 95% CI 1.4–16.3, p = 0.003), even after adjusting for potential confounders. Negative total fecal ODA status was significantly associated with elevated POx and indoxyl sulfate levels and linked to dyslipidemia, increased oxidative stress, and inflammation, which are critical contributors to CVD. Conclusions: The findings contribute novel insights into the relationship between gut microbiota’s ODA and cardiovascular health in patients undergoing KRT, emphasizing the need for further research to elucidate underlying mechanisms and explore potential therapeutic implications of targeting gut microbiota’s ODA in this vulnerable population. Full article

Titanium and metal alloys are widely used in implants, crowns, and bridges in implant dentistry owing to their biocompatibility. In this case report of a 45-year-old female patient, multiple implants were placed in five different sextants at different time points. Notably, oral lichenoid lesions (OLL) occurred in three sextants following implant placement, strongly suggesting that the dental implants or prostheses were the causative factors for OLL. The lesion was of the reticular type with erythematous surroundings and was symptomatic. Although several conservative treatments, including repeated topical application of corticosteroids, were repeatedly continued, no discernible improvement or alleviation of symptoms was observed. Consequently, surgical excision and replacement of the lesion with a free gingival graft (FGG) harvested from the palatal soft tissue were performed. No clinical symptoms or recurrence of lesions were observed during 10 years of follow-up post-FGG. Full article

Background and Objectives: The purpose of this retrospective population-based cohort study was to analyse the association between attendance of physiotherapy with mortality in the Spanish general population and describe the profile of people who do not visit a physiotherapist in Spain. Material and Methods: The data sources were the 2011/2012 National Health Survey (ENSE11) and the national database of death in Spain, and the participants were all adult respondents in the ENSE11. Results: Of 20,397 people, 1101 (5.4%) visited the physiotherapist the previous year, and the cumulative incidence of total mortality was 5.4% (n = 1107) at a mean follow-up of 6.2 years. Visiting the physiotherapist was associated with lower all-cause mortality in the population residing in Spain, quantified at 30.1% [RR = 0.699; 95% CI (0.528–0.927); p = 0.013]. The factors associated with not visiting a physiotherapist were the following: rating one’s health as good (9.8%; n = 1017; p < 0.001), not having any hospital admission in the previous year (9.6%; n = 1788; p < 0.001), not having visited the general practitioner in the previous month (9.6%; n = 1408; p < 0.001), and not having attended a day hospital in the previous year (9.7%; n = 1836; p < 0.001). Conclusions: Visiting a physiotherapist was associated with a lower mortality from all causes in the population living in Spain. Full article

Background and Objectives: Subcutaneous implantable cardioverter-defibrillators (S-ICDs) provide protection against sudden cardiac death from outside the cardiovascular system. ECG screening is a prerequisite for implantation, but the reproducibility of its results post-operatively in the device is only partial. We aimed to compare the results of ECG screening with device-based sensing vector analysis. Materials and Methods: We screened the hospital records of all S-ICD recipients in our clinic. All of them had pre-operative ECG screening performed (primary, secondary, and alternate vectors). The results were compared with device-based vector analysis to determine the relation of the pre- and post-operative vector availability. Results: Complete ECG screening and device-based vector analysis were obtained for 103 patients. At least two acceptable vectors were found in 97.1% of the patients pre-operatively and in 96.1% post-operatively. When comparing vectors in terms of agreement (OK or FAIL) pre- and post-operatively, in 89.3% of the patients, the result for the primary vector was the same in both situations; for the secondary, it was in 84.5%, and for the alternate, it was in 74.8% of patients, respectively. In 55.3% of patients, all three vectors were labeled the same (OK or FAIL); in 37.9%, two vectors had the same result, and in 6.8%, only one vector had the same result pre- and post-operatively. The number of available vectors was the same pre- and post-operatively in 62.1% of patients, while in 15.5%, it was lower, and in 22.3% of patients, it was higher than observed during screening. Conclusions: Routine clinical pre-operative screening allowed for a good selection of candidates for S-ICD implantation. All patients had at least one vector available post-operatively. The final number of vectors available in the device-based analysis in most patients was at least the same (or higher) than during screening. The repeatability of the positive result for a single vector was high. Full article

Background and Objectives: An interventional diagnostic procedure (IDP), including intracoronary acetylcholine (ACh) provocation and coronary physiological testing, is recommended as an invasive diagnostic standard for patients suspected of ischemia with no obstructive coronary arteries (INOCA). Recent guidelines suggest Thrombolysis In Myocardial Infarction frame count (TFC) as an alternative to wire-based coronary physiological indices for diagnosing coronary microvascular dysfunction. We evaluated trajectories of TFC during IDP and the impact of ACh provocation on TFC. Materials and Methods: This was a single-center, retrospective study. Patients who underwent IDP to diagnose INOCA were included and divided into two groups according to the positive or negative ACh provocation test. Wire-based invasive physiological assessment was preceded by ACh provocation tests and intracoronary isosorbide dinitrate (ISDN). We evaluated TFC at three different time points during IDP; pre-ACh, post-ISDN, and post-hyperemia. Results: Of 104 patients, 58 (55.8%) had positive ACh provocation test. In the positive ACh group, resting mean transit time (Tmn) and baseline resistance index were significantly higher than in the negative ACh group. Post-ISDN TFC was significantly correlated with resting Tmn (r = 0.31, p = 0.002). Absolute TFC values were highest at pre-ACh, followed by post-ISDN and post-hyperemia in both groups. All between-time point differences in TFC were statistically significant in both groups, except for the change from pre-ACh to post-ISDN in the positive ACh group. Conclusions: In patients suspected of INOCA, TFC was modestly correlated with Tmn, a surrogate of coronary blood flow. The positive ACh provocation test influenced coronary blood flow assessment during IDP. Full article

Background and Objectives: The diagnosis of anaphylaxis comprehensively depends on both situational information and laboratory investigations. For this purpose, serum tryptase concentration is examined as an indicator of systemic mast cell mediator release, linked to an underlying anaphylactic process. Increased levels of tryptase may occur in some events different from anaphylaxis, but usually information from crime scene investigations is lacking and autoptic findings are not specific. For legal reasons, it is required to achieve a definite diagnosis of mast cell degranulation that can lead to a certain diagnosis of death from anaphylaxis. Immunohistochemistry seems to be a relatively simple, reliable, and easily repeatable method that can assist the forensic pathologist in the differential diagnosis of death from anaphylaxis. Materials and Methods: This work provides an overview of the current literature on immunohistochemical methods useful in the determination process of anaphylactic-related deaths. A systematic search, according to the PRISMA statement, was performed in databases to identify studies investigating immunohistochemical targets related to anaphylaxis death. Results: This work underscores the importance of anaphylaxis mediators such as tryptase, CD117, and chymase in the immunohistochemical analysis of anaphylactic deaths. Conclusions: According to the reviewed literature, the diagnosis of death due to anaphylaxis should depend not just on the suspicion of an anaphylactic reaction but also on confirming mast cell degranulation through the identification of IHC positivity for inflammatory mediators, particularly in the respiratory tract. Full article

Background and Objectives: Serum vitamin levels, cardiovascular disease risk factors, and their association with depression is a complex issue that has been the subject of much research. Therefore, we investigated the relationship between vitamin A, B9, and E levels, cardiovascular risk factors, and depression in premenopausal and menopausal South Korean women. Materials and Methods: This cross-sectional study used the 2016–2018 Korea National Health and Nutrition Examination Survey data. Depression was assessed using a questionnaire to check for symptoms of depression or the Patient Health Questionnaire–9. Blood samples were collected from the antecubital vein in the morning after an overnight fast. Covariates were defined as self-reported physician diagnoses. Well-trained medical staff performed the standard procedures. Statistical analysis was performed using the complex sample analysis method of SPSS, using two separate logistic regression models (model 1: adjusted for age; model 2: adjusted for age, marital status, smoking, and alcohol consumption). Results: A total of 3313 women aged over 20 years were enrolled. The association between vitamin A levels and depression was as follows: lower levels of vitamin A were associated with an increased risk of depression in premenopausal women in model 1 and model 2. The levels of serum vitamins E and B9 were not correlated with depression in premenopausal and postmenopausal women. In the premenopausal group, depression increased in the obesity (model 1: p = 0.037; model 2: p = 0.047) and diabetes mellitus (model 1: p = 0.010; model 2: p = 0.009) groups. The menopausal group with depression had higher rates of stroke (model 1: p = 0.017; model 2: p = 0.039) and myocardial infarction (model 1: p = 0.004; model 2: p = 0.008) than the group without depression. Conclusions: Depression is correlated with lower blood levels of vitamin A in premenopausal women. Vitamin B9 and E levels were not associated with depression independent of menopausal status. Depression is associated with obesity and diabetes mellitus in premenopausal women and with stroke and myocardial infarction in postmenopausal women. Full article

Background and Objectives: Pelvic floor muscle training (PFMT) represent the first-line approach to pelvic floor dysfunctions (PFDs). Recently, studies have shown a synergy between the pelvic floor and abdominal muscles, hypothesizing that the anatomical and functional integrity of the abdominal wall plays a role in the prevention of pelvic floor disorders. Some studies have shown a significant correlation between diastasis recti abdominis (DRA) and stress urinary incontinence (SUI). Nevertheless, the evidence reported in the literature is controversial and based on low-quality data. The aim of the study is to clarify whether DRA-specific abdominal rehabilitation is needed in women with SUI after childbirth. Materials and Methods: All consecutive women who had at least one delivery and complained of symptoms of pure SUI that were urodynamically proven were considered for the study. The group of symptomatic patients was compared with a series of consecutive women, identified during the same study period, without any symptoms of SUI. In both groups, we measured the inter-rectal distance (IRD) with an ultrasound scanner above and below the navel. Results: A total of 102 women eligible for the study group and 100 women who did not report any symptoms of SUI were enrolled. The inter-rectal distance above the umbilicus showed no significant difference between the two groups (2.12 ± 0.98 vs. 2.1 ± 0.77; p = 0.94). In contrast, the data from the sub-umbilical measurements showed a significant difference. Surprisingly, the asymptomatic group showed significantly greater (0.98 ± 0.9 vs. 1.33 ± 0.87 p-value: 0.009) IRD compared to the symptomatic group. Conclusions: The study shows that DRA is not a risk factor for SUI in women after childbirth. Therefore, specific abdominal wall rehabilitation after childbirth does not seem to be indicated. Full article

Background and Objectives: The early recognition of tendon alterations in chronic hemodialysis (HD) patients, an awareness of the factors that influence the condition, and active intervention have considerable clinical relevance. The aim of this study was to investigate the musculoskeletal ultrasound (MSUS) features of the Achilles tendon in chronic HD patients and determine the factors associated with tendon abnormalities. Materials and Methods: This study was conducted on 46 HD patients and 24 sex- and age-matched controls. All participants were evaluated clinically for any signs of Achilles tendon abnormalities. Then, the Achilles tendon was scanned bilaterally using MSUS. Results: Among the 92 Achilles tendons in the HD patients, there was tenderness and swelling of only two (2.2%). Regarding MSUS features, there were statistically significant higher thicknesses in the proximal end (p < 0.001), midpoint (p < 0.001), and distal end (p < 0.001) of the Achilles tendons in the HD patients when compared with the healthy controls. Tendinosis was found in 12 (13%) of the HD patients’ Achilles tendons, which was statistically significant in comparison to the healthy controls (p = 0.008). There were statistically significant higher scores of structural abnormalities (p = 0.005), bone erosions (p = 0.017), and calcifications (p = 0.015) in the HD patients when compared to the healthy controls. According to the results of a univariate regression analysis, age and male gender were predictive for US abnormalities in HD patients (p = 0.002 and 0.025, respectively). Conclusions: The Achilles tendon in subjects on chronic HD showed frequent US abnormalities. These abnormalities in HD patients appear to be more related to age and gender and may be asymptomatic. Full article

Background and objectives: This study investigates the effects of chest mobilization and breathing exercises on respiratory function, trunk stability, and endurance in chronic stroke patients who have contracted coronavirus disease (COVID-19). Materials and Methods: Thirty inpatients of a tertiary hospital in South Korea, who had a history of COVID-19 and were diagnosed with stroke within the last 6 months, were randomly assigned to either chest mobilization exercise with breathing exercise (CMEBE) or conservative physical therapy with breathing exercise (CPTBE) groups. The respiratory function, trunk stability, and endurance were measured at baseline and 6 weeks after the interventions. Results: Both CMEBE and CPTBE groups showed improvements in respiratory function, trunk stability, and endurance after the intervention (p < 0.05). However, the CMEBE group showed significantly greater improvements in forced expiratory volume in 1 s (p < 0.05), trunk stability (p < 0.05), and endurance (p < 0.05) than the CPTBE group. No significant intergroup difference was observed in forced vital capacity and peak expiratory flow. Conclusions: The combination of chest mobilization and breathing exercises improved respiratory muscle mobility and endurance, stabilized the trunk, and enhanced balance and the transfer of weight. The findings suggest that this intervention could be beneficial in improving respiratory function and endurance in stroke patients. Full article

Point-of-care ultrasound (PoCUS) has become an indispensable standard in emergency medicine. Emergency medicine ultrasound (EMUS) is the application of bedside PoCUS by the attending emergency physician to assist in the diagnosis and management of many time-sensitive health emergencies. In many ways, using PoCUS is not only the mere application of technology, but also a fusion of already existing examiner skills and technology in the context of a patient encounter. EMUS practice can be defined using distinct anatomy-based applications. The type of applications and their complexity usually depend on local needs and resources, and practice patterns can vary significantly among regions, countries, or even continents. A different approach suggests defining EMUS in categories such as resuscitative, diagnostic, procedural guidance, symptom- or sign-based, and therapeutic. Because EMUS is practiced in a constantly evolving emergency medical setting where no two patient encounters are identical, the concept of EMUS should also be practiced in a fluid, constantly adapting manner driven by the physician treating the patient. Many recent advances in ultrasound technology have received little or no attention from the EMUS community, and several important technical advances and research findings have not been translated into routine clinical practice. The authors believe that four main areas have great potential for the future growth and development of EMUS and are worth integrating: 1. In recent years, many articles have been published on novel ultrasound applications. Only a small percentage has found its way into routine use. We will discuss two important examples: trauma ultrasound that goes beyond e-FAST and EMUS lung ultrasound for suspected pulmonary embolism. 2. The more ultrasound equipment becomes financially affordable; the more ultrasound should be incorporated into the physical examination. This merging and possibly even replacement of aspects of the classical physical exam by technology will likely outperform the isolated use of stethoscope, percussion, and auscultation. 3. The knowledge of pathophysiological processes in acute illness and ultrasound findings should be merged in clinical practice. The translation of this knowledge into practical concepts will allow us to better manage many presentations, such as hypotension or the dyspnea of unclear etiology. 4. Technical innovations such as elastography; CEUS; highly sensitive color Doppler such as M-flow, vector flow, or other novel technology; artificial intelligence; cloud-based POCUS functions; and augmented reality devices such as smart glasses should become standard in emergencies over time. Full article

Background and Objectives: Cardiac resynchronization therapy (CRT) is one of the effective therapeutic options in the treatment of systolic heart failure (HF) with persistent symptoms. This prospective study was designed to determine whether CRT with biventricular pacing would reduce the risk of development of atrial fibrillation (AF) and to identify predictors for AF occurrence. Materials and Methods: The study population consisted of 126 patients, with a mean age of 63.8 ± 9.1 years, who were eligible for CRT with biventricular pacing. Inclusion criteria were left ventricular ejection fraction (LVEF) ≤ 35%, QRS duration ≥ 130 msec, and persistent HF symptoms of New York Heart Association (NYHA) II or III, despite optimal drug therapy. Patients were followed for a period of 24 months and were evaluated through clinical, electrocardiographic, and echocardiographic examination at baseline (prior to CRT implantation), as well as at 6 and 24 months post-implantation. At the end of follow-up, patients were divided into clinical responders and non-responders based on the following criteria: decrease in NYHA class ≥ I, increase in LVEF ≥ 10%, and reduction in QRS duration ≥ 20 msec. Results: At follow-up, CRT was associated with a significant increase in LVEF (20.6 ± 6.9% pre-implantation, 32.9 ± 9.3% 24 months after implantation; p < 0.001), reduction in left ventricular end-diastolic and end-systolic diameters, and decrease in QRS duration (167.6 ± 14.3 msec pre-implantation, 131.7 ± 11.7 msec 24 months after implantation; p < 0.001), while left atrial (LA) diameter was slightly increased (p = 0.070). The frequency of AF occurrence increased after two years of follow-up (52.4% to 56.9%, p < 0.001). Significant predictors of AF occurrence in our study population were response to CRT—AF more frequent in non-responders (B = 8.134; p < 0.001), LA diameter—AF more frequent with larger LA diameter (B = 0.813; p < 0.001), and coronary sinus (CS) lead position—AF more frequent with posterolateral in comparison with lateral CS lead position (B = 5.159; p = 0.005). Conclusions: The results of our study provide new data on AF predictors in patients with HF subjected to CRT. There remains a permanent need for new predictors, which might help in patient selection and improvement in response rate. Full article

Background and Objectives: Abdominal muscle exercises with limb movements are more effective for trunk stabilization than traditional exercises involving trunk flexion alone. This study examined the effects of abdominal exercises incorporating sprinter pattern and crunch exercises on changes in the lordotic curve and abdominal muscle activation in individuals with low back pain caused by hyperlordosis resulting from weak abdominal muscles. Materials and Methods: In this single-blind, randomized controlled trial, a total of 40 participants with hyperlordosis were recruited and randomly assigned to perform either sprinter-pattern abdominal exercises or crunch exercises. The participants assigned to each group performed three sets of ten abdominal exercises. The lumbar lordotic angle (LLA) and sacrohorizontal angle (SHA) were assessed prior to and following the intervention, whereas abdominal muscle activity was gauged throughout the intervention period. Changes in the LLA and SHA were measured by radiography. Abdominal muscle activity was measured using electromyography. Results: The LLA and SHA decreased significantly in both groups (p < 0.001), while the sprinter-pattern exercise group showed a statistically significant decrease compared to the crunch exercise group (p < 0.001). In the activity of the abdominal muscles, there was no significant difference in the rectus abdominis muscle between the two groups (p > 0.005). However, a significant difference between the external and internal oblique muscles was observed, and the activities of both muscles were significantly higher in the sprinter-pattern exercise group than in the crunch exercise group (p < 0.005). Conclusions: Abdominal exercise using a sprinter pattern may be effective in reducing lumbar lordosis by strengthening the abdominal muscles in patients with hyperlordosis. Full article

Background and Objectives: Up to one-third of patients with acute biliary pancreatitis also present with choledocholithiasis. Guidelines from the European Society of Gastrointestinal Endoscopy (ESGE) and the American Society for Gastrointestinal Endoscopy (ASGE) for investigating suspected choledocholithiasis suggest endoscopic retrograde cholangiopancreatography in patients with high-likelihood (ESGE)/high-probability (ASGE) predictors and endoscopic ultrasound in those with intermediate-likelihood (ESGE)/intermediate-probability (ASGE) predictors. Although both guidelines are similar, they are not identical. Furthermore, these algorithms were mainly developed from cohorts of patients without pancreatitis and are therefore poorly validated in a subset of patients with acute pancreatitis. We aimed to assess the performance of the ESGE and ASGE algorithms for the prediction of choledocholithiasis in patients with acute biliary pancreatitis. Materials and Methods: This was a retrospective analysis of 86 consecutive patients admitted to a tertiary referral centre in the year 2020 due to acute biliary pancreatitis. Results: Choledocholithiasis was confirmed in 29/86 (33.7%) of patients (13 with endoscopic retrograde cholangiopancreatography and 16 with endoscopic ultrasound). All 10/10 (100%) ESGE high-likelihood and 14/19 (73.7%) ASGE high-probability patients had choledocholithiasis. Only 19/71 (26.8%) patients with ESGE intermediate likelihood and 15/67 (22.4%) with ASGE intermediate probability had choledocholithiasis. Only 8/13 (61.5%) patients with the ASGE high-probability predictor of dilated common bile duct plus bilirubin > 68.4 µmol/mL had choledocholithiasis. Since this predictor is not considered high likelihood by ESGE, this resulted in a superior specificity of the European compared to the American guideline (100% vs. 91.2%). Following the American instead of the European guidelines would have resulted in five unnecessary endoscopic retrograde cholangiopancreatographies and five unnecessary endoscopic ultrasound examinations. Conclusions: This retrospective analysis suggests that the European guidelines may perform better than the American guidelines at predicting choledocholithiasis in the setting of acute pancreatitis. This was because dilated common bile duct plus bilirubin > 68.4 µmol/mL was not a reliable predictor for persistent bile duct stones. Full article

Background and objectives: Multisystem inflammatory syndrome in children (MIS-C) poses challenges to the healthcare system, especially with frequent heart involvement. The current retrospective observational study aims to summarize the type and degree of cardiovascular involvement in children with MISC and to find possible associations between laboratory, inflammatory, and imaging abnormalities and the predominant clinical phenotype using a cluster analysis. Material and methods: We present a retrospective observational single-center study including 51 children meeting the MIS-C criteria. Results: Fifty-three percent of subjects presented with at least one sign of cardiovascular involvement (i.e., arterial hypotension, heart failure, pericardial effusion, myocardial dysfunction, pericarditis without effusion, myocarditis, coronaritis, palpitations, and ECG abnormalities). Acute pericarditis was found in 30/41 of the children (73%) assessed using imaging: 14/30 (46.7%) with small pericardial effusion and 16/30 (53.3%) without pericardial effusion. The levels of CRP were significantly elevated in the children with pericarditis (21.6 ± 13 mg/dL vs. 13.9 ± 11 mg/dL, p = 0.035), and the serum levels of IL-6 were higher in the children with small pericardial effusion compared to those without (191 ± 53 ng/L vs. 88 ± 27 ng/L, p = 0.041). Pericarditis with detectable pericardial effusion was significantly more frequent in the female vs. male subjects, 72% vs. 30% (p = 0.007). The hierarchical clustering analysis showed two clusters: Cluster 1 includes the children without cardiovascular symptoms, and Cluster 2 generalizes the MIS-C children with mild and severe cardiovascular involvement, combining pericarditis, myocarditis, heart failure, and low blood pressure. Also, subjects from Cluster 2 displayed significantly elevated levels of fibrinogen (5.7 ± 0.3 vs. 4.6 ± 0.3, p = 0.03) and IL-6 (158 ± 36 ng/mL vs. 66 ± 22 ng/mL, p = 0.032), inflammatory markers suggestive of a cytokine storm. Conclusions: Our results confirm that children with oligosymptomatic MIS-C or those suspected of long COVID-19 should be screened for possible cardiological involvement. Full article

Backgound and Objectives: The treatments of choice for patients with early-stage hepatocellular carcinoma (HCC) are surgical resection, local ablation therapy, and liver transplantation; however, transarterial chemoembolization (TACE) is commonly performed due to variations among patients and liver diseases. This study aimed to assess the efficacy of TACE in patients with early-stage HCC. Materials and Methods: A retrospective analysis was performed of all TACE procedures performed at Kyung Hee University Hospital at Gangdong over a 15-year period (July 2006 to November 2021). The study included a total of 97 eligible patients with early-stage HCC ≤ 5 cm initially treated with TACE. The mean participant age was 63.47 ± 11.02 years; 69 were men (71.1%). The number of Child–Pugh class A patients was the highest (74 patients [76.3%]), followed by Child–Pugh class B (19 patients [19.6%]) and Child–Pugh class C (4 patients [4.12%]). Results: A complete response was achieved in 84 (86.6%) patients after the first TACE procedure, with 1-, 2-, and 3-year survival rates of 91.8%, 87.3%, and 75.4%, respectively. In the multivariate analysis, the patients with a low initial alpha-fetoprotein (AFP) ≤ 20 ng/mL (p = 0.02) and a complete response after the first TACE (p = 0.03) were associated with favorable overall survival. Conclusions: TACE can be used to treat patients with early-stage HCC who are unsuitable for ablation or surgery. If patients are well selected, TACE may be an alternative treatment for patients with low AFP levels who respond well to the initial TACE procedure. Full article

Background and Objectives: Posterior capsular opacification (PCO) is the most common long-term complication of successful cataract surgery and can cause visual impairment. We aimed to investigate the effects of intraocular lens (IOL) characteristics on PCO by comparing the incidence of neodymium-doped yttrium aluminum garnet (Nd:YAG) laser capsulotomy for different types of intraocular lenses. Materials and Methods: A retrospective analysis was performed on 2866 eyes that underwent cataract surgery between January 2010 and December 2017, with at least 5 years of follow-up. The IOLs used for surgery were the hydrophobic lenses SN60WF (Alcon, Fort Worth, TX, USA), ZCB00 (Johnson & Johnson Vision, Santa Ana, CA, USA), and MX60 (Bausch & Lomb, Rochester, NY, USA), and the hydrophilic lens MI60 (Bausch & Lomb, Rochester, NY, USA). We analyzed the incidence of Nd:YAG laser capsulotomy according to the type of IOL used. Results: The incidence of Nd:YAG laser capsulotomy was significantly higher with MI60 lenses (31.70%, 175/552 eyes) compared to SN60WF (7.90%, 113/1431 eyes), ZCB00 (10.06%, 64/636 eyes), and MX60 (10.57%, 13/123 eyes; p < 0.001) lenses. The incidence of Nd:YAG laser capsulotomy was significantly lower with the hydrophobic IOLs (8.68%, 190/2190 eyes) than with the hydrophilic IOL (31.70%, 175/552 eyes; p < 0.001). Over time, the rate of increase in the cumulative number of Nd:YAG laser capsulotomy cases was the highest with MI60. The cumulative rate of Nd:YAG laser capsulotomy during the first 3 years was 4.90% with SN60WF (70/1431 eyes), 6.76% with ZCB00 (43/636 eyes), 8.94% with MX60 (11/123 eyes), and 26.10% with MI60 (144/552 eyes) lenses. Conclusions: The incidence of PCO is influenced by the material of the IOLs. The hydrophilic IOL was associated with a higher rate of Nd:YAG laser capsulotomy than the hydrophobic IOLs, with a shorter time to Nd:YAG laser capsulotomy. Full article

Background and Objectives: Stroke prevention has traditionally concentrated on research to improve knowledge and awareness of the disease in the general population. Since stroke incidents increase with age, there is a need to focus on the elderly, a high-risk group for developing the disease. This study aimed to examine the level of stroke awareness and knowledge, their predictors, and their source of information. Materials and Methods: A prospective cross-sectional study targeted Lebanese senior citizens aged 65 years and above. A total of 513 participants enrolled in the study through a self-administered survey distributed using a snowball sampling technique. Results: Most participants had appropriate baseline knowledge (more than 75% correct answers) of stroke, including risk factors, alarming signs, and preventive measures. Better knowledge of disease risks was significantly associated with having a university degree (ORa = 1.609; p = 0.029). Participants who had previous ischemic attacks showed significantly lower knowledge of the alarming signs (ORa = 0.467; p = 0.036) and prevention measures (ORa = 0.427; p = 0.029). Those suffering from depression had better knowledge of stroke alarming signs (ORa = 2.060.; p = 0.050). Seeking information from pharmacists, physicians, or the internet was not significantly associated with better knowledge of stroke risks, alarming signs, and preventive measures. Conclusions: The present study showed that seniors had fair knowledge of stroke, despite gaps in stroke prevention measures. Healthcare providers could play a leading role in improving public health by educating seniors to enhance awareness about prevention measures, detecting alarming signs, and acting fast to save a life. Full article

Background and Objectives: Acute cholangitis may be fatal, particularly in elderly patients. According to the Tokyo Guidelines 2018, those aged ≥75 years are classified as moderate (Grade II) severity. However, it has not been established whether age itself is the deciding factor of poor outcomes. We studied the impact of old age (≥75 years) on the mortality and morbidity of acute cholangitis due to choledocholithiasis. Materials and Methods: We retrospectively examined 260 patients with calculous acute cholangitis who had undergone biliary drainage. Patients were divided into two groups: elderly (≥75 years) and non-elderly (<75 years). We aimed to compare organ dysfunction, in-hospital mortality, intensive care unit (ICU) hospitalization, and the severity of acute cholangitis. Results: Of 260 patients, 134 (51.5%) were in the elderly group and 126 (48.5%) were in the non-elderly group. The mean age was 72.3 ± 14.4 years, and 152 (58.5%) were men. The elderly patients showed a higher incidence of shock (12.7% vs. 4.8%, p = 0.029), respiratory dysfunction (7.5% vs. 0%, p = 0.002), and renal dysfunction (8.2% vs. 0.8%, p = 0.006) than the non-elderly patients. The overall in-hospital mortality rate was 2.7%, with no significant differences between the elderly and the non-elderly (4.5% vs. 0.8%, p = 0.121). The incidence of severe acute cholangitis was significantly higher in the elderly group (26.9% vs. 9.5%, p < 0.001). However, there was no significant difference in the rates of ICU hospitalization (9.7% vs. 4%, p = 0.088) and lengths of hospital stay (LOS) (8.3 d vs. 7.1 d, p = 0.086). Conclusions: No difference was observed in the in-hospital mortality, ICU hospitalization, or LOS between the elderly (≥75 years) and the non-elderly (<75 years) with calculous acute cholangitis. However, severe acute cholangitis was significantly more frequent in elderly patients. Full article

Bone marrow failure (BMF) syndromes are a heterogeneous group of benign hematological conditions with common clinical features including reduced bone marrow cellularity and peripheral blood cytopenias. Acquired aplastic anemia (AA) is caused by T helper(Th)1-mediated immune responses and cytotoxic CD8⁺ T cell-mediated autologous immune attacks against hematopoietic stem and progenitor cells (HSPCs). Interferon-γ (IFNγ), tumor necrosis factor-α, and Fas-ligand are historically linked to AA pathogenesis because they drive Th1 and cytotoxic T cell-mediated responses and can directly induce HSPC apoptosis and differentiation block. The use of omics technologies has amplified the amount of data at the single-cell level, and knowledge on AA, and new scenarios, have been opened on “old” point of view. In this review, we summarize the current state-of-art of the pathogenic role of IFNγ in AA from initial findings to novel evidence, such as the involvement of the HIF-1α pathway, and how this knowledge can be translated in clinical practice. Full article

Background and Objectives: Cervical cancer is one of the most common types of frequently found cancers in Thailand. One of the causative agents is the infection of the high-risk human papillomavirus (HPV) type 16 and 18. Traditional medicines are rich sources of bioactive compounds which are a valuable source for the development of novel cancer therapies. In this study, the therapeutic effects of 3 traditional medicines, Kerra^TM, KS^TM, and Minoza^TM, were studied on HeLa and CaSki cells. Materials and Methods: The effects of Kerra^TM, KS^TM, and Minoza^TM on cancer cells were evaluated through cytotoxicity and cell death assays. The infection assay using HPV-16 pseudovirus was also carried out. Results: All traditional medicines efficiently suppressed cell growths of HeLa and CaSki, with Kerra^TM being the most potent anticancer agent followed by KS^TM and Minoza^TM. Kerra^TM at 158 µg/mL and 261 µg/mL significantly increases the percentage inhibition of the HPV-16 pseudovirus infection in a pre-attachment step in a dose-dependent manner, while KS^TM at 261 µg/mL efficiently inhibited viral infection in both pre-attachment and adsorption steps. However, Kerra^TM, KS^TM, and Minoza^TM at subtoxic concentrations could not reduce the viral E6 mRNA expressions of HPV-16 and HPV-18. Cell death assay by acridine orange/ethidium bromide showed that Kerra^TM increased population of dead cells in dose-dependent manner in both CaSki and HeLa. The percentage of secondary necrosis in Kerra^TM-treated CaSki was higher than that of HeLa cells, while the percentage of late apoptotic cells in HeLa was higher than that of CaSki, indicating that HeLa was more susceptible to Kerra^TM than CaSki. For KS^TM and Minoza^TM, these extracts at 250 µg/mL promoted autophagy over cell death. At 500 µg/mL, the percentage of dead cells in Kerra^TM was higher than that of KS^TM and Minoza^TM. Conclusions: Kerra^TM is a potent traditional medicine for promoting cancer cell death. Kerra^TM is possibly useful in the prevention and treatment of cervical cancer. Further investigation will be carried out to gain a better understanding of the biochemical mechanism and the pharmacological activity underlying this effect. Full article