Impact of COVID-19 Outbreak on Stoma Surgery and Stoma Clinic Service: A Retrospective Study at a Single Japanese Referral Hospital.

Aim: The impact of the COVID-19 pandemic on medical practice has been frequently reported from Western countries, but there have been few studies in other areas, especially regarding stoma surgery and stoma care. Methods: We investigated the numbers of all operations and stoma-related surgeries at our hospital in 2019 and 2020. The cumulative numbers of consultations at our ostomy clinic and patient population stratified by the period of having a stoma were compared between these calendar years. The frequency of ostomy clinic visit by individual patients within the first year after stoma creation and stoma-related complications per consultation were also analyzed. Results: The number of elective surgeries decreased by approximately 10% from 2019 to 2020, but the numbers of stoma creation and closure procedures did not differ. The total numbers of consultations at our ostomy clinic were also similar between these years. However, the percentage of patients with a stoma for less than a year who visited our ostomy clinic increased from 49.7% in 2019 to 53.5% in 2020, whereas the visitation rate for other patients decreased. Moreover, patients with a stoma for less than a year visited the ostomy clinic more frequently in 2020 (0.42/month) than in 2019 (0.30/month, p=0.032). There were fewer grade 2 or more severe peristomal complications in 2020 (11% vs 17% in 2019, p < 0.001) at our ostomy clinic. Conclusion: The COVID-19 outbreak led to a shift in the patient population at ostomy clinics of new stoma patients, which may have resulted in fewer peristomal complications.

Aneuploidy and sex concordance rate between cell-free DNA analysis from spent culture media of preimplantation embryo and DNA from whole embryo with respect to different morphological grading.

Purpose: The aneuploidy and sex concordance between cell-free DNA in spent culture media (SCM) and DNA from whole embryo with respect to different morphological grading were examined to evaluate the feasibility of non-invasive preimplantation genetic testing for aneuploidy (niPGT-A). Methods: A total of 46 pairs of embryos and corresponding SCM were divided into two groups based on the morphological grade. DNA was extracted from 22 and 24 pairs of low- and high-grade embryos, respectively, and respective SCM followed by chromosomal analysis using next-generation sequencing. Aneuploidy study and sex determination were conducted for both groups, and concordance rates were calculated. Results: For low-grade embryos, 63.6% (14/22) were determined as aneuploidy by whole embryo analysis, and concordance rates were 54.5% (12/22) using niPGT-A. On the contrary, for high-grade embryos 41.7% (10/24) were determined as aneuploidy by whole embryo analysis, and concordance rates were 62.5% (15/24) using niPGT-A. The concordance rates were not statistically different between the low-grade and high-grade embryo groups (p = 0.804). For sex determination, concordance rates between whole embryo and SCM were 81.8% (18/22) and 87.5% (21/24) in low- and high-grade groups, respectively. Conclusion: Aneuploidy and sex evaluation by niPGT-A may be feasible for both morphologically low- and high-grade embryos.

Obesity, glucose intolerance, advanced age, and lymphocytopenia are independent risk factors for oxygen requirement in Japanese patients with Coronavirus disease 2019 (COVID-19).

At the current time of rising demand for hospital beds, it is important to triage COVID-19 patients according to the treatment needed during hospitalization. The need for oxygen therapy is an important factor determining hospital admission of these patients. Our retrospective study was designed to identify risk factors associated with the progression to oxygen requirement in COVID-19 patients. A total of 133 patients with laboratory-confirmed COVID-19 were admitted to our hospital from February 22, 2020, to August 23. After excluding asymptomatic, non-Japanese, pediatric, pregnant patients and also those who needed oxygen immediately at admission, data of the remaining 84 patients were analyzed. The patients were separated into those who required oxygen after admission and those who did not, and their characteristics were compared. Age, body mass index (BMI), lymphocyte count, C-reactive protein (CRP), lactate dehydrogenase, estimated glomerular filtration rate, glucose intolerance, hypertension, and dyslipidemia were significantly different between the two groups. Multivariate analysis identified four significant and independent risk factors of oxygen requirement, including advanced age, obesity, glucose intolerance and lymphocytopenia. Dividing the patients into subgroups according to the number of these risk factors found in each patient indicated that the need for oxygen increased with higher number of these risk factors in the same individual. Our results suggest that the presence of higher number of these risk factors in COVID-19 patients is associated with future oxygen requirement and that this index can be potentially useful in triaging COVID-19 patients staying home in the context of need for hospitalization.

Four cases of Mayer-Rokitansky-Küster-Hauser syndrome treated via non-surgical vaginal reconstruction using uterine cervical dilators.

Vaginal creation is the standard treatment for Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome. Although non-surgical method is recommended as a first-line treatment in the American College of Obstetricians and Gynecologists guidelines for gynecological practice, it is not commonly performed in Japan. At our hospital, vaginal dilation using uterine cervical dilators (Hegar's dilator) is performed for patients with MRKH syndrome. We report four cases successfully treated with vaginal dilation. After the examination, patients were instructed to practice daily self-dilation at home. The initiation size was No. 13 with 10.5-mm diameter. After the vaginal cavity was dilated to a depth of 6 cm, the size of dilators was gradually increased until No. 30 with 25-mm diameter in a tip and 28-mm diameter in a trunk. The duration required to achieve the outcome was 5-22 months. All cases were successfully treated without any severe complication.

The Surprising Effect of Phenformin on Cutaneous Darkening and Characterization of Its Underlying Mechanism by a Forward Chemical Genetics Approach.

Melanin in the epidermis is known to ultimately regulate human skin pigmentation. Recently, we exploited a phenotypic-based screening system composed of ex vivo human skin cultures to search for effective materials to regulate skin pigmentation. Since a previous study reported the potent inhibitory effect of metformin on melanogenesis, we evaluated several biguanide compounds. The unexpected effect of phenformin, once used as an oral anti-diabetic drug, on cutaneous darkening motivated us to investigate its underlying mechanism utilizing a chemical genetics approach, and especially to identify alternatives to phenformin because of its risk of severe lactic acidosis. Chemical pull-down assays with phenformin-immobilized beads were performed on lysates of human epidermal keratinocytes, and subsequent mass spectrometry identified 7-dehydrocholesterol reductase (DHCR7). Consistent with this, AY9944, an inhibitor of DHCR7, was found to decrease autophagic melanosome degradation in keratinocytes and to intensely darken skin in ex vivo cultures, suggesting the involvement of cholesterol biosynthesis in the metabolism of melanosomes. Thus, our results validated the combined utilization of the phenotypic screening system and chemical genetics as a new approach to develop promising materials for brightening/lightening and/or tanning technologies.

Effectiveness of biofilm-based wound care system on wound healing in chronic wounds.

A biofilm plays a crucial role in delaying wound healing. Sharp debridement, a possible effective method for eliminating biofilms, can only be applied to the wound with visible necrotic tissue; thus, no option has been available for eliminating biofilms that are not accompanied by necrotic tissue. Wound blotting was recently developed to visualize biofilm noninvasively and quickly, and ultrasonic debridement is available for biofilm removal. Therefore, the purpose of this study was to investigate the efficacy of "biofilm-based wound care system (BWCS)," a combination of wound blotting as a point-of-care testing and ultrasonic debridement, for promoting wound healing. Firstly, the cross-sectional study was conducted to examine the proportion of biofilm removal by ultrasonic debridement in pressure ulcers [Study 1]. Subsequently, the retrospective cohort study was conducted to examine the effectiveness of BWCS for healing of chronic wounds [Study 2]. The proportions of wound healing between wounds treated with BWCS and those with standard care in the home-visiting clinic were compared by Kaplan-Meier curve, and the Cox proportional hazard modeling was used to assess the effect of BWCS on wound healing. In Study 1, the median of biofilm removal proportion was 38.9% (interquartile range, 12.9-68.0%) for pressure ulcers treated with standard care and 65.2% (41.1-78.8%) for those treated with ultrasonic debridement (p = 0.009). In Study 2, the proportion of wound healing within 90 days was significantly higher in wounds treated with BWCS than in those treated with standard care (p = 0.001). The adjusted hazard ratio of BWCS for wound healing was 4.5 (95% confidence interval, 1.3-15.0; p = 0.015). In conclusion, we demonstrated that our novel approach, BWCS, can be a promising therapeutic strategy for visualizing biofilms that are not accompanied by necrotic tissue and promoting healing in chronic wounds.

Sudden onset of sleep caused by hypothalamic infarction: a case report.

BACKGROUND: Hypothalamic lesions, such as tumors and demyelinating diseases, reportedly cause abnormal sleepiness. However, stroke involving the hypothalamus has rarely been described. Here, we report a patient with infarction restricted to the hypothalamus who presented with sudden onset of sleep. CASE PRESENTATION: A 42-year-old woman with a history of migraine without aura presented with irresistible sleepiness and developed several episodes of sudden onset of sleep. Neurological examinations were unremarkable except for partial left Horner syndrome. Brain magnetic resonance imaging (MRI) revealed a high-intensity lesion restricted to the left hypothalamus on diffusion-weighted and fluid-attenuated inversion recovery MRI images. Cerebrospinal fluid (CSF) orexin-A levels obtained on hospital day 3 after her sleepiness had resolved were normal (337 pg/mL; normal > 200 pg/mL). Serum anti-nuclear and anti-aquaporin 4 (AQP4) antibodies and CSF myelin basic protein and oligoclonal band were negative. A small hypothalamic infarction was suspected, and the patient was treated with intravenous edaravone and argatroban, as well as oral clopidogrel. Three months later, there had been no clinical relapse, and the hypothalamic lesion had almost disappeared on follow-up MRI. No new lesion suggestive of demyelinating disease or tumor was observed. CONCLUSION: Hypothalamic stroke should be considered a cause of sudden onset of sleep.

A case of primary ciliary dyskinesia treated with ICSI using testicular spermatozoa: case report and a review of the literature.

Purpose: To investigate whether or not intracytoplasmic sperm injection (ICSI) using spermatozoa extracted from testis (TESE-ICSI) is a more effective treatment than ICSI with ejaculated spermatozoa (EJ-ICSI) for primary ciliary dyskinesia (PCD). Methods: We reported a case of PCD in which we performed TESE-ICSI after repeated failure of EJ-ICSI. Together with data from previous case reports, we compared the fertilization rate and pregnancy outcome of TESE-ICSI and EJ-ICSI. Results: In our case, TESE-ICSI improved the morphology of spermatozoa and fertilization rate. However, the outcome was only a biochemical pregnancy. According to the analysis combined with previous reports, there was no difference in the fertilization rate and pregnancy outcome parameters between TESE-ICSI and EJ-ICSI. Conclusions: TESE-ICSI for PCD may improve the fertilization rate compared to EJ-ICSI. However, it does not necessarily improve the pregnancy outcome for a patient with primary ciliary dyskinesia.

Co-occurrence of multiple cerebral infarctions due to hypercoagulability associated with malignancy and meningeal carcinomatosis as the initial manifestation of gastric cancer.

BACKGROUND: Meningeal carcinomatosis and hypercoagulability associated with malignancy are typical late stage complications in cancer patients. The co-occurrence of meningeal carcinomatosis and cerebral infarction related to hypercoagulability associated with malignancy in an individual as the initial manifestation of malignancy has not been previously reported. CASE PRESENTATION: Herein, we report the case of an 80-year-old patient who presented with meningeal carcinomatosis and hypercoagulability related to malignancy as the initial manifestation of occult gastric cancer. The patient displayed consciousness disturbance, mild left facial paralysis, and bilateral positive Babinski's sign. Using brain magnetic resonance imaging, the patient was diagnosed as having acute multiple cerebral infarctions. Cerebrospinal fluid (CSF) cytology showed adenocarcinoma and upper gastrointestinal endoscopy disclosed scirrhous gastric cancer. The patient presented with headache, fever, and meningeal irritation with a subacute course. Tuberculous or fungal meningitis was initially suspected; however, cytological evidence of adenocarcinoma in the CSF led to the diagnosis of meningeal carcinomatosis. CONCLUSION: The comorbidity of hypercoagulability associated with malignancy and meningeal carcinomatosis should be considered in a patient presenting with multiple cerebral infarctions, progressive disturbance of consciousness, fever, and meningeal irritation.

Preoperative stoma site marking reduces postoperative stoma-related complications in emergency surgery: A single center retrospective cohort study.

BACKGROUND AND OBJECTIVE: Stoma site marking is an important factor in reducing stoma-related complications, thereby influencing the long-term quality of life in the elective setting. The impact of preoperative stoma site marking in emergency stoma creation is largely unknown. We aimed to determine whether preoperative stoma site marking in emergency stoma creation reduces stoma-related complications. METHODS: Patients who underwent emergency stoma creation at our hospital between 2009 and 2022 were examined by reviewing our prospective database and retrospective chart review. Subjects were classified into the "marking (+)" or "marking (-)" group according to stoma site marking (194 and 151 patients, respectively). The changes in the frequency of stoma marking over time and the effects of stoma marking on stoma-related complications were analyzed. RESULTS: The overall frequency of grade 2 or higher stoma-related complications was lower in the marking (+) group than in the marking (-) group (24% versus 36%, p = 0.010). Stoma site marking was associated with fewer soma site bleeding (2% versus 10%, p < 0.001), and the frequency of peristomal dermatitis was also lower (10%) in the marking (+) group (versus 18%, p = 0.042). Moreover, the lack of stoma site marking was an independent risk factor for overall stoma-related complications (adjusted odds ratio: 1.69, p = 0.034). CONCLUSIONS: Preoperative stoma site marking was associated with stoma-related complications in emergency surgery. The clinical significance of our attempt is worth validating with prospective studies.

Isolated shoulder palsy due to cortical infarction: a case report and literature review of clinicoradiological correlations.

Clinicoradiological correlations observed in patients with small cortical infarctions have supported somatotopic representation of different parts of body areas in primary motor cortex. However, isolated shoulder weakness because of infarction in precentral gyrus has rarely been described. We report an 80-year-old woman with isolated shoulder palsy because of cortical ischemic infarction in the base of the left precentral gyrus as confirmed by brain magnetic resonance imaging. In our patient, cardiogenic embolism or Trousseau syndrome associated with lung cancer was considered the cause of ischemic infarction. Physicians should consider small cortical infarction, when a patient complains of sudden onset of shoulder weakness without pain. In line with the previous reports, a responsible cortical lesion in our patient corresponded to motor shoulder area in the motor homunculus reported to be located more medially to the hand area.

Isolated body lateropulsion in a patient with pontine infarction.

A 72-year-old man with diabetes mellitus and hypertension was admitted to our hospital with lightheadedness. The patient showed lateropulsion to the right side, but his neurological findings were otherwise normal. Brain magnetic resonance images showed a fresh ischemic infarct in the left dorsal part of the lower pons. Body lateropulsion is characterized by an irresistible falling to one side and has been reported in lesions in several brain regions. However, it has rarely been reported in pontine lesions. We suggest that physicians should be aware that pontine lesions can cause isolated body lateropulsion without other neurological deficits.

Nod1 acts as an intracellular receptor to stimulate chemokine production and neutrophil recruitment in vivo.

Nod1 is a member of family of intracellular proteins that mediate host recognition of bacterial peptidoglycan. To characterize immune responses mediated by Nod1, synthetic ligand compounds possessing enhanced ability to stimulate Nod1 were developed to study the function of Nod1. Stimulation of epithelial cells with Nod1 stimulatory molecules induced chemokines and other proinflammatory molecules that are important for innate immune responses and recruitment of acute inflammatory cells. Administration of Nod1 ligands into mice induced chemokines and recruitment of acute inflammatory cells, an activity that was abolished in Nod1-null mice. Microarray analysis revealed that Nod1 stimulation induces a restricted number of genes in intestinal epithelial cells compared with that induced by tumor necrosis factor (TNF) alpha. Nod1 stimulation did not induce TNFalpha, interleukin 12, and interferon gamma, suggesting that the primary role of Nod1 is to induce the recruitment of immune cells. These results indicate that Nod1 functions as a pathogen recognition molecule to induce expression of molecules involved in the early stages of the innate immune response.

Sleep-related hallucinations in patients with Parkinson's disease.

Given that sleep-wake cycle dysfunction can cause hallucinations in Parkinson's disease patients, sleep-related hallucinations may be a different subtype from hallucinations that occur only during full wakefulness. However, few studies that distinguish the onset situations of hallucinations related to sleep from those that occur in full wakefulness have been conducted to investigate hallucinations in Parkinson's disease patients. Therefore, we conducted a multicenter observational study to investigate the prevalence of and factors associated with sleep-related hallucinations in patients with Parkinson's disease. Information on hallucinations was collected by using a questionnaire and face-to-face interviews. Of 100 consecutive patients with Parkinson's disease, 29 (29%) reported sleep-related hallucinations, and 16 (16%) reported hallucinations only in the full wakefulness. A longer duration of Parkinson's disease treatment (OR 1.35, 95% CI 1.07 to 1.72), higher Beck Depression Inventory-II scores (OR 1.07; 95% CI 1.01 to 1.14), and higher rapid eye movement sleep behavior disorder scores (OR 5.60; 95% CI 1.54 to 20.38) were independent factors associated with the presence of sleep-related hallucinations in a multivariable analysis. Sleep-related hallucinations, but not daytime hallucinations, were associated with probable rapid eye movement sleep behavior disorder. Phenomenological discrimination between sleep-related hallucinations and daytime hallucinations is important for elucidating the full pathology in Parkinson's disease and the mechanisms underlying hallucinations.

Limonoids and unsaturated fatty acids present in Melia toosendan increase ceramide production in keratinocytes.

The skin barrier prevents moisture evaporation and the entry of foreign substances such as allergens. Ceramides are one of the most important factors for maintaining skin barrier function. Melia toosendan is a plant of the Meliaceae family, and its fruit extracts have been used in Traditional Chinese Medicine as analgesics and anthelmintics; however, its ability to increase ceramide levels has not been reported. In this study, we screened for compounds present in M. toosendan fruit extracts that increase ceramide levels in the skin. We fractionated the extracts based on their activity to identify the active components. Nimbolinins, limonoids such as toosendanin, and hydroxylated unsaturated fatty acids were found to be the major active components. The structure-activity relationship of toosendanin derivatives indicated that the sites around R4 and R5 contributed to the activity. To the best of our knowledge, this is the first report showing that limonoids promote ceramide production in skin cells. Therefore, M. toosendan fruit extracts may be used to develop products for improving the skin barrier function.

Impact of the COVID-19 Pandemic on the Quality of Life of Patients with Parkinson's Disease and Their Caregivers: A Single-Center Survey in Tochigi Prefecture.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has negatively affected the mental health of the general population. OBJECTIVE: We investigated the determinants of quality of life (QOL) in Parkinson's disease (PD) patients during the COVID-19 pandemic. METHODS: Impacts of lifestyle changes due to the COVID-19 pandemic on 100 patients with PD and their caregivers/spouses were assessed. The Hospital Anxiety and Depression Scale was used to assess anxiety and depression. The physical component summary (PCS) and mental component summary (MCS) scores of the short form (SF)-8 were used to evaluate health-related QOL. RESULTS: Regarding health-related QOL, physical function, role physical, general health, vitality and the PCS score were significantly worse in PD patients than in caregivers. Worsening of PD-related symptoms, increased stress, and decreased physical activity were observed in 29.0%, 37.0% and 44.0% of PD patients, respectively. Sixteen patients (16.0%) experienced problems with hospital access, but none reported medication shortages. Strong concerns about COVID-19 were reported by 47.0% of caregivers and 50.0% of PD patients. In PD patients, increased gait disturbance and rigidity, disease severity, smoking, the levodopa equivalent dose and decreased body weight predicted a worse PCS score; anxiety, depression, female sex, stress and long disease duration predicted a worse MCS score. In caregivers, age and smoking contributed to a worse PCS score; depression, stress and worsening patient mood contributed to a worse MCS score. CONCLUSION: We report the negative impacts of the COVID-19 pandemic on health-related QOL and its determinants in PD patients and their caregivers.

Molecular cloning and functional characterization of porcine nucleotide-binding oligomerization domain-1 (NOD1) recognizing minimum agonists, meso-diaminopimelic acid and meso-lanthionine.

In this study, we isolated a complementary DNA encoding nucleotide-binding oligomerization domain-1 (NOD1) from Peyer's patches (Pps) of swine gut-associated lymphoid tissues (GALT). The complete open reading frame of porcine NOD1 contains 2862 bp, encoding a 953-amino acid polypeptide. The porcine NOD1 amino acid sequence is more closely related to the human sequence (83.8% identity) than the mouse counterpart (79.2% identity). To examine the subcellular expression and function of porcine NOD1, we overexpressed it in human embryonic kidney 293 cells. Immunostaining with an anti-porcine NOD1 polyclonal antibody revealed that the protein was expressed in transfectants as an intracellular membrane-bound molecule. In the transfected cells, both gamma-d-glutamyl-meso-diaminopimelic acid, and meso-diaminopimelic acid and meso-lanthionine activated nuclear factor-kappa B. Quantitative real-time PCR detected NOD1 mRNA in multiple tissues isolated from adult and newborn swine, including the esophagus, duodenum, jejunum, ileum, ileal Pps, colon, spleen, and mesenteric lymph nodes. In the newborn and adults, NOD1 was highly expressed in the esophagus and GALT, such in the ileal Pps and mesenteric lymph nodes. Furthermore, Toll-like receptor and NOD1 ligands as well as immunobiotic lactic acid bacteria enhanced the expression of NOD1 in GALT of adult and newborn swine. Our results should help clarify how the intestinal immune system is modulated by low-molecular weight peptidoglycan fragments through NOD1.

[Efficacy of oral cavity care in preventing stomatitis (mucositis) in cancer chemotherapy].

Stomatitis is a common side effect during cancer chemotherapy. We hypothesized that careful oral cavity care using patient guidance and cleanliness index prevents stomatitis in cancer chemotherapy. We introduced oral care patient guidance including teaching good brushing methods, O'Leary's Plaque Control Record(PCR)as a cleanliness index, and Eilers' Oral Assessment Guide(OAG)as an overall index after April 2006. We evaluated the incidence of stomatitis in 20 patients(10 patients between April 2004 to May 2006 and 10 patients after April 2006)with esophageal cancer who received chemotherapy including 5-FU and CDDP. Patients receiving brushing training after 2006 were evaluated regarding cleanliness of their oral cavities using PCR index and OAG index. The rates of stomatitis were 60%(6/10)and 40%(4/10)before and after the introduction of oral care patient guidance. The average of PCR index decreased from 82% to 46% after teaching good brushing method to the patients. The average of OAG index after brushing training was 9.14 which was better score compared with previous reports. Introduction of oral care patient guidance decreased the incidence of stomatitis. Both PCR and OAG indexes were useful in evaluating the objective condition of the oral cavity and in sharing patients' information among a medical team. These indexes encouraged the patients to clean their oral cavities.