RhoA, Claudin 18, and c-MET in Gastric Cancer: Clinicopathological Characteristics and Prognostic Significance in Curative Resected Patients

Background: Recently, markers related to molecular classification were suggested as promising therapeutic targets for treatment and prediction of prognosis in gastric cancer (GC), including c-MET, RhoA, and Claudin-18 (CLDN18). This study aimed to investigate their expression in GC and its correlation with clinicopathological characteristics and survival. Methods: We retrospectively evaluated GC patients who underwent curative gastrectomy. c-MET, RhoA, and CLDN18 were analyzed through immunohistochemistry (IHC), and groups for analysis were determined according to the median values obtained for each marker. Results: Among the 349 GC evaluated, 180 (51.6%), 59 (16.9%), and 61 (17.5%) patients were completely negative for c-MET, RhoA, and CLDN18, respectively. Total gastrectomy, D1 lymphadenectomy, poorly differentiated histology, and greater inflammatory infiltrate were more frequent in the c-MET-negative group. Diffuse type, greater inflammatory infiltrate, and advanced pT and pTNM stage were associated with low-RhoA GC. The venous invasion was more frequent in the low-CLDN18 group. Furthermore, c-MET was positively correlated with RhoA and negatively with CLDN18. HER2 expression was associated with c-MET-positive and high-CLDN18 GC; and loss of E-cadherin expression in c-MET-negative and low-RhoA GC. c-MET-negative and Low-RhoA were significantly associated with worse disease-free survival. Conclusions: c-MET, RhoA, and CLD18 expression occurred frequently in GC. RhoA GC had distinct clinicopathological characteristics related to prognosis. c-MET and RhoA were associated with survival but were not independent predictors of prognosis.

Nitric Oxide: The Missing Factor in COVID-19 Severity?

Coronavirus disease 2019 (COVID-19) is a contagious respiratory and vascular disease that continues to spread among people around the world, mutating into new strains with increased transmission rates, such as the delta variant. The scientific community is struggling to discover the link between negative COVID-19 outcomes in patients with preexisting conditions, as well as identify the cause of the negative clinical patient outcomes (patients who need medical attention, including hospitalization) in what seems like a widespread range of COVID-19 symptoms that manifest atypically to any preexisting respiratory tract infectious diseases known so far. Having successfully developed a nutritional formulation intervention based on nitrate, a nitric oxide precursor, the authors hypothesis is that both the comorbidities associated with negative clinical patient outcomes and symptoms associated with COVID-19 sickness are linked to the depletion of a simple molecule: nitric oxide.

ARNI Pre-Operative Use and Vasoplegic Syndrome in Patients Undergoing Heart Transplantation or Left Ventricular Assist Device Surgery

Background: Vasoplegic syndrome after orthotopic heart transplantation (OHT) or left ventricular assist device (LVAD) implantation is a rare but highly lethal syndrome with complex etiologies. The objective of this study was to assess if the preoperative use of sacubitril-valsartan combination is associated with an increased vasoplegic syndrome (VS) frequency after OHT or LVAD implantation and its relationship with 30-day mortality. Methods: A retrospective review of perioperative data, between January 2016 and December 2017, from 73 consecutive OHT and LVAD surgery adult patients at our institution was performed. VS was defined as normal cardiac output with persistent low systemic resistance requiring a norepinephrine intravenous perfusion > 0.5 µg/kg/min and the absence of sepsis or hemorrhagic shock within 48 h after surgery. Patients were all followed-up for adverse events and all-cause mortality at 30 days. Results: In our cohort of 73 patients (median age 51.7 years, 65% male patients), 25 (34%) patients developed VS. Twenty-two (30.1%) patients were on ARNI at the time of surgery, 31 (42.5%) were on other RAS blockers, 12 (16.4%) were on norepinephrine and 8 (11%) had no pre-operative drug. The pre-operative use of any vasoactive agent, was not significantly associated with VS (OR = 1.36; IC95% [0.78; 2.35]; p = 0.38). The pre-operative use of an ARNI compared to all other groups was not significantly associated with VS (OR = 2.0; IC95% [0.71; 5.62]; p = 0.19). The pre-operative use of an ARNI compared to other RAS blockers was also not significantly associated with VS (OR = 1.25; IC95% [0.37; 4.26]; p = 0.72). At 30 days, 18 (24.7%) patients had died. The pre-operative treatment with ARNI, or other RAS inhibitors was associated with a significantly lower rate of death compared to the absence of treatment (HR = 0.11; IC95% [0.02; 0.55]; p = 0.009 for ARNI and HR = 0.20; IC95% [0.06; 0.69]; p = 0.011 for other RASi). Conclusions: Preoperative use of sacubitril-valsartan was not significantly associated with development of vasoplegic syndrome in patients undergoing OHT or LVAD surgery. Furthermore, our data suggests a significant 30-day survival benefit with efficient renin-angiotensin blockade before surgery.

Safety of Insulin Degludec/Insulin Aspart in Patients with Diabetes Mellitus over a Period of 1 Year during Routine Clinical Care in India: SMART (Study of Management of Diabetes with Ryzodeg™ Treatment)

This post-authorization study was conducted to evaluate the safety of insulin degludec/insulin aspart (IDegAsp) in adult patients with diabetes mellitus (DM) during routine clinical care under a real-world setting in India. Eligible patients received IDegAsp for a minimum of 12 months during routine clinical management. Data were collected at 0, 3, 6, and 12 months. In total, 1029 adult patients with DM were included; 65.2% (n = 671) were men; mean age was 55.0 ± 12.2 years, and the mean duration of diabetes mellitus was 10.8 ± 7.4 years. Thirty adverse events were reported in 23 patients (2.2%) during the follow-up: two adverse events in two patients were serious with fatal outcomes, which were unrelated to IDegAsp use. At baseline, there were 176 confirmed hypoglycemic events in 67 (6.7%) patients while they were on their previous treatment options. At 12 months of treatment with IDegAsp, 11 confirmed hypoglycemic events were reported in 11 (1.1%) patients since the previous visit; there were no reported episodes of severe hypoglycemia. Mean glycosylated hemoglobin value reduced from 9.5% ± 1.8% at baseline to 7.7% ± 1.1% at 12 months. This study showed the safety of IDegAsp in patients with diabetes mellitus over a period of 1 year during routine clinical care.

Nutrients, Cognitive Function, and Brain Aging: What We Have Learned from Dogs

Due to a difference in genetics, environmental factors, and nutrition, just like in people, dogs age at different rates. Brain aging in people and dogs share similar morphological changes including irreversible cortical atrophy, cerebral amyloid angiopathy, and ventricular enlargement. Due to severe and irreversible brain atrophy, some aging dogs develop cognitive dysfunction syndrome (CDS), which is equivalent to dementia or Alzheimer’s disease (AD) in people. The risk factors and causes of CDS in dogs have not been fully investigated, but age, gender, oxidative stress, and deficiency of sex hormones appears to be associated with increased risk of accelerated brain aging and CDS in dogs. Both AD and CDS are incurable diseases at this moment, therefore more efforts should be focused on preventing or reducing brain atrophy and minimizing the risk of AD in people and CDS in dogs. Since brain atrophy leads to irreversible cognitive decline and dementia, an optimal nutritional solution should be able to not only enhance cognitive function during aging but also reduce irreversible brain atrophy. Up to now, only one nutritional intervention has demonstrated both cognition-enhancing benefits and atrophy-reducing benefits.

Wound Healing and Therapy in Soft Tissue Defects of the Hand and Foot from a Surgical Point of View

Wounds and tissue defects of the hand and foot often lead to severe functional impairment of the affected extremity. Next to general principles of wound healing, special functional and anatomic considerations must be taken into account in the treatment of wounds in these anatomical regions to achieve a satisfactory reconstructive result. In this article, we outline the concept of wound healing and focus on the special aspects to be considered in wounds of the hand and foot. An overview of different treatment and dressing techniques is given with special emphasis on the reconstruction of damaged structures by plastic surgical means.

Removal of a Giant Cyst of the Left Ovary from a Pregnant Woman in the First Trimester by Laparoscopic Surgery under Spinal Anesthesia during the COVID-19 Pandemic

This paper reports a case of a 21 year old primigravida at 6 weeks gestation, suffering from important abdominal pain, who was admitted into the medical center with a giant cyst of 28 × 20 cm on her left ovary. A torsion of the ovarian cyst was suspected. Her COVID-19 status was unknown. In view of the emergency of the situation and the COVID-19 pandemic, laparoscopy in spinal anesthesia was performed. The patient remained conscious during the surgical intervention and tolerated it well apart from a slight dyspnea, which was easily eliminated by changing her body position and decreasing the pneumoperitoneum pressure. The ovarian cyst was removed by enlarging the trocar incision. The patient recovered with neither incident nor pregnancy loss. COVID-19-related complications can induce adverse pregnancy outcomes. Under general anesthesia, patients with COVID-19 are at risk of severe pneumonia and of passing their infection to the medical personnel. To avoid such complications in non-specialized centers, laparoscopy should be performed in regional anesthesia. Laparoscopy in spinal anesthesia can be performed safely on pregnant patients by placing them in the proper position, using a low pneumoperitoneum, and monitoring the hemodynamics. During early pregnancy, general anesthesia induces a higher risk of teratogenic effects and of miscarriage.

Trabecular Bone Score and Bone Mineral Density in Postmenopausal Women with Morbid Obesity—A Clinical Paradox

Obesity has long been considered to have a protective effect on bone, but specific complications in those with morbid obesity are known to have a detrimental impact on bone architecture. We aimed to study the bone microarchitecture (TBS—trabecular bone score) and bone mineral density (BMD) in postmenopausal women with morbid obesity compared to obese and non-obese age-matched women. Eighty-five consecutive postmenopausal women with morbid obesity (body mass index (BMI) ≥ 35 kg/m2) were enrolled and compared to age-matched obese (n = 80) and non-obese postmenopausal controls (n = 85). The BMD and TBS were assessed in all subjects using a Hologic-QDR 4500-W Discovery-A DXA scanner. The mean BMD (gm/cm2) at the femoral neck in women with morbid obesity was found to be significantly lower as compared to the age-matched postmenopausal obese controls (0.723 versus 0.762, p-value = 0.002). The BMD at the lumbar spine and hip showed similar trends but were not statistically significant. The bone microarchitecture was found to be significantly lower in those with morbid obesity (1.205) as compared to the other two groups (obesity 1.244; non-obese 1.228) (p < 0.013). Though obesity was associated with a better bone density and bone microarchitecture in postmenopausal women, a paradoxical lower value was seen in those with morbid obesity.

Post-Coronavirus Disease-2019 (COVID-19): Toward a Severe Multi-Level Health Crisis?

There were already numerous challenges facing the healthcare system prior to the ongoing coronavirus disease-2019 (COVID-19) pandemic. Although we look forward to ending this pandemic, it is still expected that the healthcare system will face further challenges leading to a multi-level health crisis. Indeed, after the COVID-19 pandemic, there will still be COVID-19 active cases and those left with health problems following COVID-19 infection who will be of a particular impact. In addition, we also have the health problems that either emerged or worsened during COVID-19, especially with the reduced ability of the healthcare system to take care of many non COVID-19 patients during the COVID-19 pandemic. Such expected evolution of the situation highlights the necessity for the decision-makers to consider applying serious reforms and take quick measures to prevent a post-COVID-19 health crisis.

Sodium Chloride, Migraine and Salt Withdrawal: Controversy and Insights

This paper examines evidence implicating migraine headache as a withdrawal symptom of excessive sodium chloride intake. Emerging research in food addiction posits that food and drug addictions share common features, such as withdrawal symptoms. Salt (sodium chloride) meets the criteria for the diagnosis of substance dependence, including withdrawal in which the substance is used to relieve withdrawal symptoms. The premonitory symptoms of migraine include food cravings for salty foods, which can alleviate migraine pain. Edema, possibly related to large amounts of salt consumed in binge eating, can cause approximately four pounds of retained fluid. This amount of fluid is similar to the fluid retained before the onset of migraine headache, which may be accompanied by polyuria. This paper proposes that inhibited withdrawal from highly processed food intake, rich in salt, mediates an association between increased sodium chloride intake and relief from migraine headache pain. The relief from withdrawal symptoms could also be a mediating factor that explains the controversial findings inversely associating dietary sodium intake with migraine history. Moreover, the withdrawal of retained sodium and edema related to the use of nonsteroidal anti-inflammatory drugs may elucidate a potential mechanism in medication overuse headache. Further research is needed to investigate the pain experienced from sodium chloride withdrawal in migraine headache.