Medicina, Volume 57, Issue 4 (April 2021) – 97 articles

Dyshidrosiform bullous pemphigoid is a variant of bullous pemphigoid. At least 84 patients with dyshidrosiform bullous pemphigoid have been described. Dyshidrosiform bullous pemphigoid usually presents with pruritic blisters in elderly individuals; the hemorrhagic or purpuric lesions on the palms and soles can be the only manifestation of the disease. However, bullae may concurrently or subsequently appear on other areas of the patient’s body. Patients typically improve after the diagnosis is established and treatment is initiated. The mainstay of therapy is systemic corticosteroids, with or without topical corticosteroids, and systemic dapsone or immunosuppressants. Drug-related or nickel-induced dyshidrosiform bullous pemphigoid improves after stopping the associated agent; however, systemic therapy has also been required to achieve resolution of the blisters. Similar to classic bullous pemphigoid, neurologic conditions and psychiatric disorders have been observed in dyshidrosiform bullous pemphigoid patients. The new onset of recurrent or persistent blisters on the palms, soles, or both of an elderly individual should prompt the clinician to consider the diagnosis of dyshidrosiform bullous pemphigoid. Full article

Alpha-1 antitrypsin (AAT) has established anti-inflammatory and immunomodulatory effects in chronic obstructive pulmonary disease but there is increasing evidence of its role in other inflammatory and immune-mediated conditions, like diabetes mellitus (DM). AAT activity is altered in both developing and established type 1 diabetes mellitus (T1DM) as well in established type 2 DM (T2DM). Augmentation therapy with AAT appears to favorably impact T1DM development in mice models and to affect β-cell function and inflammation in humans with T1DM. The role of AAT in T2DM is less clear, but AAT activity appears to be reduced in T2DM. This article reviews these associations and emerging therapeutic strategies using AAT to treat DM. Full article

Background and Objectives: The aetiology and pathomechanism of fibromyalgia syndrome 12 (FMS) as one of chronic pain syndromes still need to be further elucidated. Mitogen-activated protein kinase (MAPK) pathway has been proposed as a novel approach in pain management. Since the major symptom of fibromyalgia syndrome (FMS) patients is pain, it became of interest whether MAPK pathways, such as the stress-activated p38 MAPK/MK2 axis, are activated in FMS patients. Therefore, this study aimed at determining p38 MAPK/MK2 in FMS patients. Materials and Methods: Phosphorylation of MAPK-activated protein kinases 2 (MK2), a direct target of p38 MAPK, was measured in monocytes of FMS and healthy controls (HCs) to monitor the activity of this pathway. Results: The mean level of phosphorylated MK2 was fivefold higher in FMS patients as compared to HCs (p < 0.001). Subgroup analysis revealed that antidepressants did not influence the activity of MK2 in FMS patients. Conclusions: This result indicates that the p38/MK2 pathway could be involved in the pathomechanism of FMS, could act as a clinical marker for FMS, and could be a possible target for pain management in FMS patients. Full article

Background and Objectives: At present, thyroid disorders have a great incidence in the worldwide population, so the development of alternative methods for improving the diagnosis process is necessary. Materials and Methods: For this purpose, we developed an ensemble method that fused two deep learning models, one based on convolutional neural network and the other based on transfer learning. For the first model, called 5-CNN, we developed an efficient end-to-end trained model with five convolutional layers, while for the second model, the pre-trained VGG-19 architecture was repurposed, optimized and trained. We trained and validated our models using a dataset of ultrasound images consisting of four types of thyroidal images: autoimmune, nodular, micro-nodular, and normal. Results: Excellent results were obtained by the ensemble CNN-VGG method, which outperformed the 5-CNN and VGG-19 models: 97.35% for the overall test accuracy with an overall specificity of 98.43%, sensitivity of 95.75%, positive and negative predictive value of 95.41%, and 98.05%. The micro average areas under each receiver operating characteristic curves was 0.96. The results were also validated by two physicians: an endocrinologist and a pediatrician. Conclusions: We proposed a new deep learning study for classifying ultrasound thyroidal images to assist physicians in the diagnosis process. Full article

Background and Objectives: In the general population, sleep disorders are associated with lower urinary tract symptoms (LUTS) including urinary incontinence (UI). This connection has not been explored fully in specific patient groups. Thus, we investigated the association between sleep quality and LUTS for patients with depression. Materials and Methods: This study was prospective and cross-sectional. We analyzed questionnaire data on depression, sleep quality, LUTS, and UI from depressed patients treated in our department of adult psychiatry. We used the Hamilton Rating Scale for Depression, the Holland Sleep Disorders Questionnaire, the International Prostate Symptom Score, and the International Consultation on Incontinence Questionnaire-Short Form. Results: In total, 102 patients treated for depression were enrolled. We found a statistically significant correlation between depression severity and sleep quality. A significant correlation was also investigated for sleep quality and LUTS severity. The group of depressed patients with moderate or severe LUTS had greater sleep problems compared with patients who had mild urinary tract symptoms or no symptoms. With regression analysis, we further demonstrated that the relationships between LUTS and sleep quality as well as UI and sleep quality in depressed patients are independent from age and sex. Conclusions: In the cohort of patients treated for depression, sleep quality correlated with LUTS including UI. We suggest that the negative effect of LUTS and UI on sleep quality that we observed should lead to the re-evaluation of current recommendations for diagnosis and treatment of sleep problems among patients with depression. Full article

Optimizing the diagnosis of lung cancer represents a challenge, as well as a necessity, for improving the low survival of these patients. Flexible bronchoscopy with forceps biopsy is one of the key diagnostic procedures used for lung tumors. The small sample size and crush artifacts are several factors that can often limit access to a complete diagnosis, therefore leading to the need of repeating the bronchoscopy procedure or other invasive diagnostic methods. The bronchoscopic cryobiopsy is a recent technique that proved its utility in the diagnosis of both endobronchial and peripheral lung tumors. In comparison with conventional forceps biopsy, studies report a higher diagnostic yield and a superior quality of the collected samples for both the histopathological and the molecular diagnosis of lung cancer. This method shows promising results in sampling lung tissue, alone, or in conjunction with fluoroscopy or radial endobronchial ultrasound (r-EBUS). With a good safety and cost-benefit profile, this novel method has the potential to improve the diagnosis, and therefore the management of lung cancer patients. The objective of this narrative review is to provide a comprehensive review of the recent data regarding the advantages of cryobiopsy and r-EBUS in lung cancer diagnosis. Full article

Background and Objectives: The rising numbers of laparoscopic sleeve gastrectomy (LSG) procedures now being performed worldwide will likely be followed by an increasing number of patients experiencing gastro-esophageal reflux disease (GERD). The purpose of the current review was to analyze in terms of safety different techniques of fundoplication used to treat GERD associated with LSG. Methods: An online search was performed in PubMed/MEDLINE in December 2020 to identify articles reporting LSG and fundoplication. The following term combination was used: (sleeve, fundoplication), (sleeve, Nissen), (sleeve, Rossetti), (sleeve, Toupet) and (sleeve, Dor). The extracted information included details of the methods (e.g., retrospective case series), demographic characteristics (e.g., age, gender), clinical characteristics, number of patients, rate of conversion, and postoperative outcomes. Results: A total of 154 studies were identified and after an assessment of title according to our exclusion criteria, 116 articles were removed. Of the 38 studies analyzed for full content review, a total of seven primary studies (487 patients) were identified with all inclusion criteria. Analyzing the different types of fundoplication used, we have identified: 236 cases of Nissen-Sleeve, 220 cases with modified Rossetti fundoplication, 31 cases of Dor fundoplication, and no case of Toupet fundoplication. The overall postoperative complication rate was 9.4%, with the most common reported complication being gastric perforation, 15 cases—3.1%. The second most common complication was bleeding identified in nine cases (1.8%) followed by gastric stenosis in six cases (1.2%). The mortality was nil. Conclusions: Different types of fundoplication associated with LSG appear to be a safe surgical technique with an acceptable early postoperative complication rate. Any type of fundoplication associated with LSG to decrease GERD should be evaluated cautiously while prospective clinical randomized trials are needed. Full article

Background and Objectives: Burning mouth syndrome (BMS) is an enigmatic, idiopathic, chronic, often painful clinical entity, where patients experience oral burning without clear clinical changes on the oral mucosa. There are yet to be well established standardized and validated definitions, diagnostic criteria or classifications for burning mouth syndrome. The aim of this study is to determine whether vitamin B complex and zinc supplements or 0.02% topical capsaicin rinse, can help alleviate BMS pain/burning levels. The objectives: (1) Gather data before and after treatment with vitamin B complex and zinc supplements (2) After the vitamin B complex and zinc protocol gather data before and after treatment with 0.02% topical capsaicin rinse (3) Data analysis and assessment for both treatment methods. Materials and Methods: 89 patients took part in the vitamin B and zinc supplement treatment regimen, out of those 20 patients took part in the capsaicin rinse treatment regimen. Before and after each treatment pain/burning levels were determined using the Visual analogue scale, salivary flow was also determined. Results: Both treatment methods showed statistically significant data in reducing pain/burning levels. There were no statistically significant changes in the salivary flow after any treatment. Conclusion: vitamin B and zinc supplement therapy and topical capsaicin rinse therapy can be an effective way to decrease pain/burning sensation levels in patients with BMS. More research should be conducted to determine the benefit of either vitamin B and zinc supplement therapy or topical capsaicin rinse therapy, so that BMS patients have treatment options, that have as few side-effects as possible. Full article

Low-dose acetylsalicylic acid (ASA) is widely used during pregnancy to prevent obstetric complications of placental dysfunction, such as preeclampsia, stillbirth and fetal growth restriction, and obstetric complications in pregnant women with antiphospholipid syndrome. ASA-sensitive pregnant women cannot benefit from the effects of ASA due to the possibility of severe or potentially life-threatening hypersensitivity reactions to ASA. ASA desensitization is a valuable and safe therapeutic option for these women, allowing them to start daily prophylaxis with ASA and prevent pregnancy complications. The authors discuss the recent advances in obstetric conditions preventable by ASA and the management of ASA hypersensitivity in pregnancy, including ASA desensitization. To encourage the implementation of ASA desensitization protocols in ASA-sensitive pregnant women, they also propose a practical approach for use in daily clinical practice. Full article

Background and objective: The recent availability of data from mass-participation running events has allowed researchers to examine pacing from the perspective of non-elite distance runners. Based on an extensive analysis of the literature, we concluded that no study utilizing mass-participation events data has ever directly compared pacing in the 10-km race, with other long-distance races. Therefore, the main aim of this study was to assess and compare pacing between 10-km runners and marathoners, in regards to their sex and age. Materials and methods: For the purpose of this study, official results from the Oslo marathon (n = 8828) and 10-km race (n = 16,315) held from 2015 to 2018 were included. Results: Both 10-km runners and marathoners showed positive pacing strategies. Moreover, two-way analysis of variance showed that women were less likely to slow in the marathon than men (9.85% in comparison to 12.70%) however, not in the 10-km race (3.99% in comparison to 3.38%). Finally, pace changing is more prominent in youngest and oldest marathoners comparing to the other age groups (12.55% in comparison to 10.96%). Conclusions: Based on these findings, practitioners should adopt different training programmes for marathoners in comparison to shorter long-distance runners. Full article

This report addresses the extent to which there may be scope for preventive programmes for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), and, if so, what economic benefits may accrue from the implementation of such programmes. We consider the economic case for prevention programmes, whether there is scope for preventive programmes for ME/CFS, and what are the health and economic benefits to be derived from the implementation of such programmes. We conclude that there is little scope for primary prevention programmes, given that ME/CFS is attributable to a combination of host and environmental risk factors, with host factors appearing to be most prominent, and that there are few identified modifiable risk factors that could be the focus of such programmes. The exception is in the use of agricultural chemicals, particularly organophosphates, where there is scope for intervention, and where Europe-wide programmes of health education to encourage safe use would be beneficial. There is a need for more research on risk factors for ME/CFS to establish a basis for the development of primary prevention programmes, particularly in respect of occupational risk factors. Secondary prevention offers the greatest scope for intervention, to minimise diagnostic delays associated with prolonged illness, increased severity, and increased costs. Full article

Every woman needs to know about the importance of the function of pelvic-floor muscles and pelvic organ prolapse prevention, especially pregnant women because parity and labor are the factors which have the biggest influence on having pelvic organ prolapse in the future. In this article, we searched for methods of training and rehabilitation in prepartum and postpartum periods and their effectiveness. The search for publications in English was made in two databases during the period from August 2020 to October 2020 in Cochrane Library and PubMed. 77 articles were left in total after selection—9 systematic reviews and 68 clinical trials. Existing full-text papers were reviewed after this selection. Unfinished randomized clinical trials, those which were designed as strategies for national health systems, and those which were not pelvic-floor muscle-training-specified were excluded after this step. Most trials were high to moderate overall risk of bias. Many of reviews had low quality of evidence. Despite clinical heterogeneity among the clinical trials, pelvic-floor muscle training shows promising results. Most of the studies demonstrate the positive effect of pelvic-floor muscle training in prepartum and postpartum periods on pelvic-floor dysfunction prevention, in particular in urinary incontinence symptoms. However more high-quality, standardized, long-follow-up-period studies are needed. Full article

The past one hundred years have seen tremendous improvements in burn care, allowing for decreased morbidity and mortality of this pathology. The more prominent advancements occurred in the period spanning 1930–1980; notably burn resuscitation, early tangential excision, and use of topical antibiotic dressings; and are well documented in burn literature. This article explores the advancements of the past 40 years and the areas of burn management that are presently topics of active discussion and research. Full article

Background and Objectives: Ovarian surgical ablation (OSA) in estrogen receptor-positive (ER+) breast cancer is usually performed to halt ovarian function in premenopausal patients. Since alternative pharmacological therapy exists and few studies have investigated why surgery is still performed, we aimed to analyze the reasons for the use of OSA despite the remaining controversy. Materials and Methods: Premenopausal ER+ breast cancer patients treated at a tertiary center (2005–2011) were selected, and patients with germline mutations were excluded. Results: Seventy-nine patients met the inclusion criteria. Globally, the main reasons for OSA included: continued menstruation despite hormone therapy with or without ovarian medical ablation (OMA) (34.2%), patient informed choice (31.6%), disease progression (16.5%), gynecological disease requiring surgery (13.9%), and tamoxifen intolerance/contraindication (3.8%). In women aged ≥45 years, patient choice was significantly more frequently the reason for OSA (47.4% versus 17.1% (p = 0.004)). For those aged <45 years, salvation attempts were significantly more frequent as compared to older women (26.8% versus 5.3% (p = 0.01)). In 77.8% of women undergoing OSA with menstrual cycle maintenance, surgery was performed 1–5 years after diagnosis, while surgery was performed earlier (0–3 months after diagnosis) in patients undergoing OSA as an informed choice (56.0%), as a salvation attempt (53.8%), or due to gynecological disease (63.6%). The leading reason for OSA in women previously undergoing OMA was continued menstruation (60.0%). Conclusions: This study suggests a possible failure of pharmacological ovarian suppression and reinforces the need for shared decision-making with patients when discussing treatment strategies, although validation by further studies is warranted due to our limited sample size. Full article

Background and Objectives: An inter-arm systolic blood pressure difference (IASBPD) is defined as a blood pressure (BP) disparity of ≥10 mmHg between arms. IASBPDs are associated with an increased risk of cardiovascular disease (CVD). Similarly, visceral fat accumulation (VFA) is clinically important because it is associated with higher cardiovascular disease risk. Accordingly, this study compared the body composition parameters of IASBPD individuals with individuals who did not express an IASBPD. Materials and Methods: The analysis included 104 patients. The blood pressures of all participants were measured simultaneously in both arms using automated oscillometric devices. Then patients were divided into two groups according to their IASBPD status: Group 1 (IASBPD− (<10 mmHg)); Group 2 (IASPPD+ (≥10 mmHg)). Body composition parameters were measured using bioelectrical impedance analysis. Results: In 42 (40%) patients, the simultaneously measured IASBPD was equal to or higher than 10 mmHg. The right brachial SBP was higher in 63% of patients. There were no differences between the groups in terms of demographic and clinical characteristics. Regarding the two groups’ body composition parameter differences, VFA was significantly higher in group 2 (p = 0.014). Conclusions: The IASBPD is known to be associated with an increased risk of cardiovascular events. Although the body mass indexes (BMIs) of the two groups were similar, VFA levels in those with a greater than 10 mmHg IASBPD were found to be significantly higher. This finding may explain the increased cardiovascular risk in this group. Full article

Background and objectives: The pineal gland is a photoneuroendocrine organ in the midline of the brain, responsible primarily for melatonin synthesis. It is composed mainly of pinealocytes and glial tissue. This study examined human postmortem pineal glands to microscopically assess age-related changes using digital techniques, and offers a perspective on evolutionary tendencies compared to the past. Materials and Methods: A retrospective autopsy study has been performed on 72 pediatric and adult autopsy cases. The glands have been processed for histological analysis and immunohistochemical staining with glial fibrillary acidic protein (GFAP). Slides were assessed under polarized light and digitally scanned. Morphometric data were obtained using CaseViewer and ImageJ. Results: Thirty-three females and 39 males were included in the study, grouped under three age groups: 0–25, 46–65, and 66–96 years of age. The peak gland volume was found within the 46–65 age group, the overall mean volume was 519 mm³, the main architectural types were lobular and insular, and the mean percentage of pineal calcification was 15% of the gland, peaking within the 66–96 age group, with a predominantly globular shape. Glial cysts were found in 20.8% of cases. The intensity of GFAP stain was maximal in the pediatric age group, but the extent of glial tissue was much larger in elderly patients. Discussion: The degenerative process of the pineal gland can be quantified by measuring normal parenchyma, calcifications, glial tissue, and glial cysts. Morphometric differences have been observed and compared to a similar studies performed in the published literature. The current study, unfortunately, lacks a 26–45 age group. Digital techniques seemed to offer a more exact analysis, but returned similar results to studies performed over 40 years ago, therefore offering important information on evolutionary tendencies. Conclusions: Increase in glial tissue, calcifications, and glial cysts have a defining role as age-related changes in the pineal gland. Full article

Holistic and life-long medical surveillance is the core of personalised medicine and supports an optimal implementation of both preventive and curative healthcare. Personal medical records are only partially unified by hospital or general practitioner informatics systems, but only for citizens with long-term permanent residence. Otherwise, insight into the medical history of patients greatly depends on their medical archive and memory. Additionally, occupational exposure records are not combined with clinical or general practitioner records. Environmental exposure starts preconceptionally and continues during pregnancy by transplacental exposure. Antenatal exposure is partially dependent on parental lifestyle, residence and occupation. Newborn screening (NBS) is currently being performed in developed countries and includes testing for rare genetic, hormone-related, and metabolic conditions. Transplacental exposure to substances such as endocrine disruptors, air pollutants and drugs may have life-long health consequences. However, despite the recognised impact of transplacental exposure on the increased risk of metabolic syndrome, neurobehavioral disorders as well as immunodisturbances including allergy and infertility, not a single test within NBS is geared toward detecting biomarkers of exposure (xenobiotics or their metabolites, nutrients) or effect such as oestradiol, testosterone and cytokines, known for being associated with various health risks and disturbed by transplacental xenobiotic exposures. The outcomes of ongoing exposome projects might be exploited to this purpose. Developing and using a OneHealth Medical Record (OneHealth^MR) may allow the incorporated chip to harvest information from different sources, with high integration added value for health prevention and care: environmental exposures, occupational health records as well as diagnostics of chronic diseases, allergies and medication usages, from birth and throughout life. Such a concept may present legal and ethical issues pertaining to personal data protection, requiring no significant investments and exploits available technologies and algorithms, putting emphasis on the prevention and integration of environmental exposure and health data. Full article

Gestational diabetes mellitus (GDM) is recognized as one of the most common medical complications of pregnancy that can lead to significant short-term and long-term risks for the mother and the fetus if not detected early and treated appropriately. Current evidence suggests that, with the use of appropriate screening programs for GDM, those women diagnosed and treated have reduced perinatal morbidity. It has been implied that, when screening for GDM, there should be uniformity in the testing used and in further management. This paper summarizes and compares current screening strategies proposed by international bodies and discusses application in the context of the COVID-19 pandemic. Full article

Thermal injuries have been a phenomenon intertwined with the human condition since the dawn of our species. Autologous skin translocation, also known as skin grafting, has played an important role in burn wound management and has a rich history of its own. In fact, some of the oldest known medical texts describe ancient methods of skin translocation. In this article, we examine how skin grafting has evolved from its origins of necessity in the ancient world to the well-calibrated tool utilized in modern medicine. The popularity of skin grafting has ebbed and flowed multiple times throughout history, often suppressed for cultural, religious, pseudo-scientific, or anecdotal reasons. It was not until the 1800s, that skin grafting was widely accepted as a safe and effective treatment for wound management, and shortly thereafter for burn injuries. In the nineteenth and twentieth centuries skin grafting advanced considerably, accelerated by exponential medical progress and the occurrence of man-made disasters and global warfare. The introduction of surgical instruments specifically designed for skin grafting gave surgeons more control over the depth and consistency of harvested tissues, vastly improving outcomes. The invention of powered surgical instruments, such as the electric dermatome, reduced technical barriers for many surgeons, allowing the practice of skin grafting to be extended ubiquitously from a small group of technically gifted reconstructive surgeons to nearly all interested sub-specialists. The subsequent development of biologic and synthetic skin substitutes have been spurred onward by the clinical challenges unique to burn care: recurrent graft failure, microbial wound colonization, and limited donor site availability. These improvements have laid the framework for more advanced forms of tissue engineering including micrografts, cultured skin grafts, aerosolized skin cell application, and stem-cell impregnated dermal matrices. In this article, we will explore the convoluted journey that modern skin grafting has taken and potential future directions the procedure may yet go. Full article

Background and objectives: The latest reports suggest that follitropin delta is a highly efficient recombinant human follicle-stimulating hormone (r-hFSH) that became a part of the current assisted reproductive technologies (ARTs). Therefore, the present study aims to assess a series of parameters (follicles, oocytes, and embryos) and further by the outcomes in women following the administration of follitropin delta. Materials and methods: This observational study included 205 women. They were aged between 21 and 43 years (mean 33.45) and an anti-Müllerian hormone (AMH) level ranging from 0.11 to 16.00 ng/dL (mean 2.89). Results: In accordance with the established methodology and following the centralization of data, a total of fifty-eight pregnancies (28.29%) were achieved; forty-five (36.88%) were achieved in women under 35 years and thirteen (15.66%) in women above 35 years. These figures are positively correlated with women’s age considering that the number of follicles >18 mm, oocytes fertilized and embryo(s) varies among groups. Regarding the interest parameters, we noted n = 1719 follicles > 18 mm, n = 1279 retrieved oocytes, and n = 677 embryos at day 3. On the other hand, the following figures have been registered in women above 35 years: 814–follicles > 18 mm, 612 oocytes retrieved and 301 embryos at day 3. During this study, we registered only three cases of abortions (n = 1–0.81% in women under 35 years and n = 2–2.40% in women above 35 years). Nine pregnancies (7.37%) were stopped from evolution in females under 35 years, and twelve pregnancies (n = 8–6.55% in women under 35 years, while n = 4 in women above 35 years) were unsuccessful. A twin pregnancy has been confirmed (1.20%) in women above 35 years, six ongoing pregnancies (4.91%) in those under 35 years, and two in both groups (one per group–n = 1–0.81%, and 1.20%–n = 1) in which we did not know the exact result were registered at the end of the established studied interval. However, there were also situations in which the treatment cause an over-reactivity or had no effect; n = 2 were non-responders, and n = 1 exhibited moderate ovarian hyperstimulation syndrome (OHSS). Conclusions: Based on our results, we strongly encourage the use of this recombinant gonadotropin on a much larger scale. Full article

Pain is managed using a biopsychosocial approach and pharmacological and non-pharmacological treatments. Transcutaneous electrical nerve stimulation (TENS) is a technique whereby pulsed electrical currents are administered through the intact surface of the skin with the intention of alleviating pain, akin to ‘electrically rubbing pain away’. Despite over 50 years of published research, uncertainty about the clinical efficacy of TENS remains. The purpose of this comprehensive review is to critically appraise clinical research on TENS to inform future strategies to resolve the ‘efficacy-impasse’. The principles and practices of TENS are described to provide context for readers unfamiliar with TENS treatment. The findings of systematic reviews evaluating TENS are described from a historical perspective to provide context for a critical evaluation of factors influencing the outcomes of randomized controlled trials (RCTs); including sample populations, outcome measures, TENS techniques, and comparator interventions. Three possibilities are offered to resolve the impasse. Firstly, to conduct large multi-centered RCTs using an enriched enrolment with randomized withdrawal design, that incorporates a ‘run-in phase’ to screen for potential TENS responders and to optimise TENS treatment according to individual need. Secondly, to meta-analyze published RCT data, irrespective of type of pain, to determine whether TENS reduces the intensity of pain during stimulation, and to include a detailed assessment of levels of certainty and precision. Thirdly, to concede that it may be impossible to determine efficacy due to insurmountable methodological, logistical and financial challenges. The consequences to clinicians, policy makers and funders of this third scenario are discussed. I argue that patients will continue to use TENS irrespective of the views of clinicians, policy makers, funders or guideline panel recommendations, because TENS is readily available without prescription; TENS generates a pleasant sensory experience that is similar to easing pain using warming and cooling techniques; and technological developments such as smart wearable TENS devices will improve usability in the future. Thus, research is needed on how best to integrate TENS into existing pain management strategies by analyzing data of TENS usage by expert-patients in real-world settings. Full article

About 422 million people worldwide have diabetes and approximately one-third of them have a major risk factor for diabetic foot ulcers, including poor sensation in their feet from peripheral neuropathy and/or poor perfusion to their feet from peripheral artery disease. The current healthcare ecosystem, which is centered on the treatment of established foot disease, often fails to adequately control key reversible risk factors to prevent diabetic foot ulcers leading to unacceptable high foot disease amputation rate, 40% recurrence of ulcers rate in the first year, and high hospital admissions. Thus, the latest diabetic foot ulcer guidelines emphasize that a paradigm shift in research priority from siloed hospital treatments to innovative integrated community prevention is now critical to address the high diabetic foot ulcer burden. The widespread uptake and acceptance of wearable and digital health technologies provide a means to timely monitor major risk factors associated with diabetic foot ulcer, empower patients in self-care, and effectively deliver the remote monitoring and multi-disciplinary prevention needed for those at-risk people and address the health care access disadvantage that people living in remote areas. This narrative review paper summarizes some of the latest innovations in three specific areas, including technologies supporting triaging high-risk patients, technologies supporting care in place, and technologies empowering self-care. While many of these technologies are still in infancy, we anticipate that in response to the Coronavirus Disease 2019 pandemic and current unmet needs to decentralize care for people with foot disease, we will see a new wave of innovations in the area of digital health, smart wearables, telehealth technologies, and “hospital-at-home” care delivery model. These technologies will be quickly adopted at scale to improve remote management of diabetic foot ulcers, smartly triaging those who need to be seen in outpatient or inpatient clinics, and supporting acute or subacute care at home. Full article

Headache is a common finding in the postpartum period, caused by a spectrum of different conditions. Most headaches in the postpartum period are self-limiting and benign in etiology, but there are some potentially serious causes to be considered. We disclose two cases of postpartum headache, initially considered as post-dural puncture headache (PDPH), that evolved into a harmful condition and showed that an expanded differential diagnosis for headache in the postpartum is mandatory, requiring a high level of attention from health professionals. In fact, a careful examination of the medical history, physical examination, and the recognition for the need for early neuroradiological imaging should increase diagnostic accuracy. Full article

Background and Objectives: Heart failure with preserved ejection fraction (HFpEF) remains a worldwide management problem. Although there is a general effort for characterizing this population, few studies have assessed the predictive value of the echocardiographic E/e’ ratio in patients with acute HFpEF. The aim of the study was to identify groups with different prognosis in patients hospitalized with a first acute episode of HFpEF. Materials and Methods: The primary endpoint of the study was heart failure readmissions (HFR) at 6 months, while the secondary outcome was six-month mortality. We consecutively enrolled 91 patients hospitalized for the first time with acute HFpEF. We examined the E/e’ ratio as an independent predictor for HFR using univariate regression. Results: We identified and validated the E/e’ ratio as an independent predictor for HFR. An E/e’ ratio threshold value of 13.80 was calculated [(area under the receiver operating characteristic curve (AUROC) = 0.693, sensitivity = 78.60%, specificity = 55%, p < 0.004)] and validated as an inflection point for an increased number of HFR. Thus, we divided the study cohort into two groups: group 1 with an E/e’ ratio < 13.80 (n = 39) and group 2 with an E/e’ ratio > 13.80 (n = 49). Compared to group 1, group 2 had an increased number of HFR (p = 0.003) and a shorter time to first HFR (p = 0.002). However, this parameter did not influence all-cause mortality within six months (p = 0.84). Conclusions: The dimensionless E/e’ ratio is a useful discriminator between patients with acute HFpEF. An E/e’ value over 13.80 represents a simple, yet effective instrument for assessing the HFR risk. However, all-cause mortality at six months is not influenced by the E/e’ ratio. Full article

Backgrounds and Objectives: The epidemiology and prognostic role of lingual lymph node (LLN) metastasis in patients with oral squamous cell carcinoma (OSCC) remain unclear. Here, we aimed to analyze the clinicopathological features, risk factors, and prognostic role of LLN metastasis in patients with OSCC. Materials and Methods: In total, 945 patients with OSCC were retrospectively analyzed. Clinicopathological features were compared between patients with and without LLN metastasis. The risk factors of LLN metastasis and its effects on survival outcomes were evaluated using multi-variate analysis. Results: LLN metastasis was noted in 67 patients (7.1%). Habitual alcohol consumption and clinical neck node metastasis were independent risk factors for LLN metastasis. LLN metastasis was an independent prognostic factor for disease-free and overall survival, although LLN dissection did not improve survival outcomes. Conclusion: LLN metastasis is an independent adverse prognostic factor. Further prospective studies are needed to fully assess the extent of LLN dissection required in OSCC patients. Full article

Background and Objectives: The jumping kick of Taekwondo was a unilateral exercise that repeatedly moves in one direction. The exercise was exposed to the risk of injury due to the heavy ground reaction force and load in the landing. The first purpose of this study was to compare the impact force (IF), peak vertical ground reaction force (PVGRF), vertical loading rate (VLR), vertical stiffness (VS), and landing foot angle (LFA) during the landing of the jumping kick according to the experience of lower injury. The second purpose of this study was to investigate the lower extremities’ strength and the bilateral/ipsilateral asymmetry between the groups; Material and Methods: Ten injury-experience athletes (IG, age: 21.0 ± 0.8 years; height: 170.5 ± 4.1 cm; body weight: 66.7 ± 6.0 kg; career: 8.1 ± 5.0 years) and seven non-injury experience athletes (NG, age: 22.9 ± 4.0 years; height: 173.4 ± 3.1 cm; body weight: 67.9 ± 7.9 kg; career: 8.3 ± 5.0 years) participated; Results: There was no statistical difference between the two groups in the landing and lower extremity muscle strength impact variables. However, in the bilateral asymmetry of the ankle plantar flexor and the ipsilateral asymmetry of the hip abductor/adductor, IG was statistically larger than NG (p < 0.05). The landing foot angle also showed negative correlation to all impact variables (IF, PVGRF, VLR, and VS) (p < 0.05); Conclusions: It is desirable to place the landing foot down at a wide angle to prevent injury in performing Taekwondo jumping kicks. Although NGs have been shown to have better muscle strength symmetry and balance in some areas compared to IG, further research is needed to determine whether they are effective in preventing injury. Full article

Both laboratory investigations and body composition quantification measures (e.g., computed tomography, CT) portray muscle loss in symptomatic Coronavirus disease 2019 (COVID-19) patients. Muscle loss is associated with a poor prognosis of the disease. The exact mechanism of muscle damage in COVID-19 patients, as well as the long-term consequences of muscle injury in disease survivors, are unclear. The current review briefly summarizes the literature for mechanisms, assessment measures, and interventions relevant to skeletal muscle insult in COVID-19 patients. Muscle injury is likely to be attributed to the cytokine storm, disease severity, malnutrition, prolonged physical inactivity during intensive care unit (ICU) stays, mechanical ventilation, and myotoxic drugs (e.g., dexamethasone). It has been assessed by imaging and non-imaging techniques (e.g., CT and electromyography), physical performance tests (e.g., six-minute walk test), anthropometric measures (e.g., calf circumference), and biomarkers of muscle dystrophy (e.g., creatine kinase). Interventions directed toward minimizing muscle loss among COVID-19 patients are lacking. However, limited evidence shows that respiratory rehabilitation improves respiratory function, muscle strength, quality of life, and anxiety symptoms in recovering older COVID-19 patients. Neuromuscular electrical stimulation may restore muscle condition in ICU-admitted patients, albeit empirical evidence is needed. Given the contribution of malnutrition to disease severity and muscle damage, providing proper nutritional management for emaciated patients may be one of the key issues to achieve a better prognosis and prevent the after-effects of the disease. Considerable attention to longer-term consequences of muscle injury in recovering COVID-19 patients is necessary. Full article

Background and Objectives: Breast cancer (BC) remains one of the major causes of cancer death in women worldwide. The difficulties in assessing the deep molecular mechanisms involved in this pathology arise from its high complexity and diverse tissue subtypes. Long non-coding RNAs (lncRNAs) were shown to have great tissue specificity, being differentially expressed within the BC tissue subtypes. Materials and Methods: Herein, we performed lncRNA profiling by PCR array in triple negative breast cancer (TNBC) and luminal A tissue samples from 18 BC patients (nine TNBC and nine luminal A), followed by individual validation in BC tissue and cell lines. Tissue samples were previously archived in formalin-fixed paraffin-embedded (FFPE) samples, and the areas of interest were dissected using laser capture microdissection (LCM) technology. Results: Two lncRNAs (OTX2-AS1 and SOX2OT) were differentially expressed in the profiling analysis (fold change of 205.22 and 0.02, respectively, p < 0.05 in both cases); however, they did not reach statistical significance in the individual validation measurement (p > 0.05) when analyzed with specific individual assays. In addition, GAS5 and NEAT1 lncRNAs were individually assessed as they were previously described in the literature as being associated with BC. GAS5 was significantly downregulated in both TNBC tissues and cell lines compared to luminal A samples, while NEAT1 was significantly downregulated only in TNBC cells vs. luminal A. Conclusions: Therefore, we identified GAS5 lncRNA as having a differential expression in TNBC tissues and cells compared to luminal A, with possible implications in the molecular mechanisms of the TNBC subtype. This proof of principle study also suggests that LCM could be a useful technique for limiting the sample heterogeneity for lncRNA gene expression analysis in BC FFPE tissues. Future studies of larger cohort sizes are needed in order to assess the biomarker potential of lncRNA GAS5 in BC. Full article

Elastofibroma dorsi (ED) is known as a particular clinical and biological entity. We report a case of a bilateral elastofibroma dorsi (ED) in a 65-year-old female who presented to the Department of General and Oncologic Surgery of Emergency Clinical Municipal Hospital Timisoara, Romania. The patient was symptomatic on the right side, presenting pain in the interscapulothoracic region associated with a variable tumoral mass, dependent on the position of the right arm. Imaging studies revealed a well-defined, bilateral tumoral mass with alternation of the muscular and fatty tissue. The initial diagnosis of lipoma was taken into consideration based on the CT scan and clinical findings. Surgical excision of the right subscapular tumor was performed without any postoperative complications. Microscopic examination of hematoxylin and eosin, Masson’s trichrome, and orcein stained slides revealed the diagnosis of ED. Considering the high rate of reported postoperative complications and the asymptomatic presentation of the contralateral subscapular mass, the patient underwent clinical and imagistic monitoring for the contralateral tumor. Due to its rare nature, ED is a difficult preoperative diagnosis that can, however, be suggested by its specific location and may require an accurate histopathological examination for a final diagnosis. Full article

Background and objectives: the aim of this study was to analyze the efficacy of a modified “amnion-assisted conjunctival epithelial redirection (ACER)” technique for the treatment of partial limbal stem cell deficiency (LSCD). Materials and methods: the medical records of three patients with partial LSCD who underwent corneal surface reconstruction with modified ACER following superficial keratectomy were retrospectively studied. Briefly, in this technique, an inner amniotic membrane (AM) layer was applied on the corneal surface to promote corneal re-epithelialization. The outer AM layer was applied as a barrier to prevent the invasion of conjunctival epithelial cells into the cornea before the corneal surface was completely covered by corneal epithelial cells derived from the remaining intact limbal stem cells. Results: in all three cases, the outer AM layer successfully kept the conjunctival epithelium away from the corneal surface and prevented an admixture of conjunctival epithelial cells with corneal epithelial cells. In all three patients, the cornea was completely re-epithelized with epithelial cells derived from the remaining healthy limbal stem cells, and a clear visual axis was maintained without recurrence for a mean follow-up period of 37.3 ± 8.6 months. Conclusions: the preliminary results suggest that modified ACER appears to be a viable option for patients with partial LSCD. Full article