Comprehensive analysis of long COVID in a Japanese nationwide prospective cohort study.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread rapidly since 2019, and the number of reports regarding long COVID has increased. Although the distribution of long COVID depends on patient characteristics, epidemiological data on Japanese patients are limited. Hence, this study aimed to investigate the distribution of long COVID in Japanese patients. This study is the first nationwide Japanese prospective cohort study on long COVID. METHODS: This multicenter, prospective cohort study enrolled hospitalized COVID-19 patients aged ≥18 years at 26 Japanese medical institutions. In total, 1200 patients were enrolled. Clinical information and patient-reported outcomes were collected from medical records, paper questionnaires, and smartphone applications. RESULTS: We collected data from 1066 cases with both medical records and patient-reported outcomes. The proportion of patients with at least one symptom decreased chronologically from 93.9% (947/1009) during hospitalization to 46.3% (433/935), 40.5% (350/865), and 33.0% (239/724) at 3, 6, and 12 months, respectively. Patients with at least one long COVID symptom showed lower quality of life and scored higher on assessments for depression, anxiety, and fear of COVID-19. Female sex, middle age (41-64 years), oxygen requirement, and critical condition during hospitalization were risk factors for long COVID. CONCLUSIONS: This study elucidated the symptom distribution and risks of long COVID in the Japanese population. This study provides reference data for future studies of long COVID in Japan.

Annexin A1 is a cell-intrinsic metalloregulator of zinc in human ILC2s.

Group 2 innate lymphoid cells (ILC2s) produce large amounts of type 2 cytokines including interleukin-5 (IL-5) and IL-13 in response to various stimuli, causing allergic and eosinophilic diseases. However, the cell-intrinsic regulatory mechanisms of human ILC2s remain unclear. Here, we analyze human ILC2s derived from different tissues and pathological conditions and identify ANXA1, encoding annexin A1, as a commonly highly expressed gene in non-activated ILC2s. The expression of ANXA1 decreases when ILC2s activate, but it increases autonomously as the activation subsides. Lentiviral vector-based gene transfer experiments show that ANXA1 suppresses the activation of human ILC2s. Mechanistically, ANXA1 regulates the expression of the metallothionein family genes, including MT2A, which modulate intracellular zinc homeostasis. Furthermore, increased intracellular zinc levels play an essential role in the activation of human ILC2s by promoting the mitogen-activated protein kinase (MAPK) and nuclear factor κB (NF-κB) pathways and GATA3 expression. Thus, the ANXA1/MT2A/zinc pathway is identified as a cell-intrinsic metalloregulatory mechanism for human ILC2s.

A prospective clinical study evaluating short-term changes in body composition and quality of life after gastrectomy in elderly patients receiving postoperative exercise and nutritional therapies.

BACKGROUND: Muscle mass loss after gastrectomy is associated with a negative impact on quality of life (QOL) and long-term prognosis following gastric cancer treatment, especially in elderly patients. We conducted a prospective study to examine short-term changes in body composition and QOL after gastrectomy in elderly patients with gastric cancer who received exercise and nutritional therapies. METHODS: Patients over aged 65 years of age who underwent gastrectomies for gastric cancer were enrolled in our study. Patients received exercise and nutritional therapies with branched-chain amino acid (BCAA)-rich supplements during 1 month after surgery. Body composition was evaluated using InBody S10 before surgery, and at 1 week and 1 month postoperatively. Other variables including QOL status (EQ-5D-5 L), serum albumin level, hand grip strength, and gait speed were evaluated at the same time. RESULTS: Eighteen patients were analyzed. The mean loss of skeletal muscle mass index (SMI) was 4.6% (1 week) and 2.1% (1 month) compared to the preoperative period. QOL scores showed almost the same degree of recovery at 1 month after gastrectomy as preoperative scores. Serum albumin levels, hand grip strength, and gait speed decreased at 1 week and then increased at 1 month after surgery, similar to the changes seen in SMI. CONCLUSIONS: Multidisciplinary approaches play key role in the surgical treatment of elderly patients. Postoperative exercise and nutritional therapies with BCAA-rich supplements may benefit elderly patients after gastrectomy by reducing loss of SMI and decreases in QOL. TRIAL REGISTRATION: UMIN Clinical Trials Registry; UMIN000034374 (registration date: 10/10/2018).

Risk factors associating with delayed gastric emptying after laparoscopic distal gastrectomy.

PURPOSE: The aim of this study was to investigate the incidence of delayed gastric emptying among the patients receiving laparoscopic distal gastrectomy, and to explore their clinical features and risk factors. METHODS: Clinical data were collected for 223 patients who underwent laparoscopic distal gastrectomy for gastric cancer. We retrospectively evaluated the clinicopathological features and analyzed the incidence of delayed gastric emptying among 223 patients. Delayed gastric emptying was diagnosed by patient's symptoms and the plane radiograph with an air fluid level and dilation of the remnant stomach. RESULTS: Delayed gastric emptying was found in five (2.2%) of the 223 patients. By univariate logistic regression analysis, greater American Society of Anesthesiologists Physical Status (ASA-PS) and older age were significantly related to occurrence of delayed gastric emptying. By multivariate logistic regression analysis, older age was independently significantly related to incident delayed gastric emptying. The area under the curve (AUC) ((95% CI) of the receiver operating characteristic (ROC) was 0.842 (0.561-0.957). The best cutoff for discriminating patients with and without delayed gastric emptying was 80 years (sensitivity 80% and specificity 83%). CONCLUSION: Our study found the occurrence of delayed gastric emptying is possibly correlated with age. Therefore, careful perioperative observation in elderly patients may possibly be important for possible development of delayed gastric emptying after laparoscopic distal gastrectomy.

How Can Dupilumab Cause Eosinophilic Pneumonia?

Reports of eosinophilic pneumonia (EP) as a side effect of dupilumab administration are limited in previous studies. Herein, we report two cases in which EP developed subsequent to the administration of dupilumab for eosinophilic chronic rhinosinusitis (ECRS). Case 1: A 55-year-old woman presented with ECRS, eosinophilic otitis media, and bronchial asthma, and was treated with dupilumab for ECRS. Five weeks later, fever and dyspnea developed, and infiltration shadows were observed in her lungs. The peripheral blood eosinophil count (PBEC) was 3848/µL (26%), bronchoalveolar lavage fluid showed eosinophilic infiltration, and EP was subsequently diagnosed. Her condition improved following prednisolone treatment. Case 2: A 59-year-old man presented with fatigue and dyspnea after receiving dupilumab for ECRS. He had infiltrative shadows throughout his left lung field, and his PBEC was 4850/µL (26.5%). Prednisolone was initiated, and his condition improved. EP developed in both patients during the period of elevated PBEC after dupilumab administration, and dupilumab was suspected to be the causative agent in their EP. Hence, EP should be considered as a differential diagnosis when fever and dyspnea appear following dupilumab administration.

Current overview of the role of neuropeptides in ILC2s and future directions.

The neural and immune systems are closely connected, and recently, their molecular mechanisms and relationships with diseases have attracted substantial attention. Particularly, it has been increasingly reported that ILC2s, which produce type 2 cytokines independent of acquired immunity, are regulated by neuropeptides such as catecholamines, acetylcholine, vasoactive intestinal peptide, neuromedins, and calcitonin gene-related peptide. However, the regulatory mechanisms in this regard are only partially understood, implying that further studies are still needed to clarify the complete mechanisms and processes. In this review, we summarize current reports on the regulatory effect of neuropeptides on ILC2s, some of which have conflicting results, possibly owing to the complexity of G-protein coupled receptors. By summarizing the current evidence, we hope to be able to identify what is currently unknown as well as what needs to be clarified in the future.

Smooth muscle degeneration of the mesenteric and branching veins causing ischemic enteritis: a case report.

BACKGROUND: Ischemic bowel injuries are generally caused by arteriosclerosis, thromboembolism, or vasculitis. Ischemic enteritis is less common than ischemic colitis because of the rich collateral arteries of the small intestine. In the present case, smooth muscle degeneration of the mesenteric to the submucosal veins caused ischemic enteritis and small bowel obstruction. CASE PRESENTATION: An 85-year-old woman with recurrent enteritis eventually developed small bowel obstruction. We performed laparoscopic partial resection of the small intestine. The pathological findings revealed smooth muscle degeneration of the mesenteric veins that caused ischemic enteritis. Venous changes were detected not only in the injured region, but also in a part of the normal region of the resected specimen. She continued to experience some minor symptoms postoperatively; however, these symptoms subsided in a short period with medicine discontinuation. CONCLUSION: This report shows the possibility that a disease causes ischemic enteritis with unique venous pathological changes and may recur postoperatively.

Repair of a perineal hernia with a bladder patch after abdominoperineal resection: A case report and literature review.

Perineal hernia is the protrusion of the intra-abdominal viscera through the pelvic floor. It rarely occurs after abdominoperineal resection but has increasingly occurred after surgical treatment for rectal cancer. A patient was diagnosed as having perineal hernia 10 days after laparoscopic abdominoperineal resection with preoperative radiotherapy and chemotherapy. He presented with epigastric discomfort and perineal wound dehiscence. Perineal hernia was confirmed by computed tomography scan and treated with a semi-emergency surgery. The surgical field was contaminated because of the perineal wound dehiscence. The levator muscle at the pelvic floor was not sufficient, so we used a bladder patch to cover the pelvic inlet. The surgery was performed without any adverse events. To our best knowledge, this is the first case report to present the usefulness of a bladder patch for the treatment of a perineal hernia using a laparoscopic transabdominal approach in emergency situations.

Anal tuberculosis presenting as refractory perianal abscess.

Although most cases occur in immunocompromised individuals, anal tuberculosis can occur in the absence of HIV infection. Anal tuberculosis should be considered in the differential diagnosis of chronic or recurrent anal fistulas.

Gram staining of gallbladder bile samples is useful for predicting surgical site infection in acute cholecystitis patients undergoing an early cholecystectomy.

BACKGROUND: Microbiological assessment of gallbladder bile is important for postoperative management in cholecystectomy for acute cholecystitis (AC). Gram staining is used as the first step in the assessment, in order to preliminarily detect bacteria in the bile sample. This study was conducted to evaluate the clinical significance of Gram staining results in the development of postoperative surgical site infection (SSI) in AC patients. METHODS: A total of 428 AC patients, who underwent an early cholecystectomy with microbiological assessment of gallbladder bile, were enrolled in this retrospective study. The clinical usefulness of the Gram staining results was evaluated by univariate and multivariate regression analyses. RESULTS: Of the 428 patients, 298 patients (69.6%) were diagnosed with bile infection by the Gram staining method. The rate of SSI was higher in patients with bile infection (9.7%) than in those without the infection (0.8%). The multivariate analysis indicated that the bile infection diagnosed by Gram staining (odds ratio: 9.091; P = .033) was an independent factor to predict SSI development, along with open surgery. CONCLUSIONS: Gram staining diagnosis of bile infection in an early cholecystectomy for AC is useful for predicting postoperative SSI development, which should benefit postoperative management.

Pulmonary Intravascular Large B-cell Lymphoma in a Patient Administered Methotrexate for Rheumatoid Arthritis.

A 70-year-old woman with rheumatoid arthritis undergoing methotrexate (MTX) treatment presented with dyspnea and a subfever. Computed tomography (CT) revealed a diffuse minimal ground-glass appearance in both lungs and splenomegaly. The gallium scintigram showed a diffuse, mild uptake in both lungs and the spleen. The lung biopsy specimen revealed the presence of CD20-positive atypical lymphocytes in the small pulmonary vessels. The patient was diagnosed with pulmonary intravascular diffuse large B-cell lymphoma (IVLBCL) and exhibited spontaneous regression after MTX was discontinued. This report describes a rare case of MTX-associated lymphoproliferative disorder expressing pulmonary IVLBCL.

Dementia in elderly patients undergoing early cholecystectomy for acute cholecystitis: a retrospective observational study.

BACKGROUND: Dementia often adversely affects postoperative outcomes in surgical patients. This study evaluated postoperative outcomes among elderly patients with and without dementia undergoing early cholecystectomy for acute cholecystitis (AC). METHODS: A total of 182 patients over 85 years of age who were diagnosed with AC and treated from January 2005 to March 2018 were reviewed retrospectively; 59 patients who underwent early cholecystectomy were enrolled. The complication rates, length of postoperative hospital stay, and rates of routine discharge (i.e., returning to their preoperative living location) were compared between two groups of patients with and without dementia. RESULTS: The overall complication rate after early cholecystectomy for AC in 59 patients was 11.9%, and there was no mortality in this series. The median postoperative hospital stay was 9.0 days, and the routine discharge rate was 89.8%. Of the 59 patients, 22 patients (37.3%) had a history of dementia. Complication rates were comparable between the groups, despite the rate of delirium development being significantly higher in the dementia group. The median length of postoperative hospital stay and routine discharge rates did not significantly differ between groups. CONCLUSIONS: Early cholecystectomy for patients with AC over 85 years of age was performed safely, and elderly patients with dementia had similar postoperative outcomes as compared with patients without dementia.

Abscopal effect of radiation on multiple lung metastases of lung adenocarcinoma: a case report.

BACKGROUND: Abscopal effect is the out-of-field response to localized irradiation therapy that results in systemic antitumorigenic effects such as the regression of a tumor distant from the target site. CASE PRESENTATION: A 76-year-old woman was diagnosed with pulmonary adenocarcinoma (cT1bN0M0 stage IA), and right upper lobectomy was performed in November 2015. The pathological stage was pT1bN2M0 stage IIIA. Genomic analysis revealed an EGFR mutation. Immunohistochemical analysis revealed a programmed death-ligand 1 tumor proportion score of < 1%. The patient was under watchful observation without adjuvant chemotherapy. Multiple mediastinal and right hilar lymph node metastases were found in February 2018. Radiation therapy at a total dose of 60.0 Gy distributed in 30 fractions was performed over a period of 6 weeks. A computed tomography (CT) scan performed 6 weeks after irradiation therapy showed a reduction in lymph node metastases. However, left hilar and right supraclavicular lymph node metastases and multiple pulmonary metastases were newly observed outside of the irradiation field. A CT scan performed 6 weeks later showed a dramatic complete disappearance of the previously observed pulmonary metastases. No chemotherapy was administered during the period. CONCLUSION: This was a case of abscopal effect: irradiation of the mediastinum resulted in the disappearance of multiple pulmonary metastases in both lungs.

A resected case of recurrent ITPN in the remnant pancreas after pancreatoduodenectomy.

BACKGROUND: Since intraductal tubulopapillary neoplasm (ITPN) is a rare disease, the clinical features of ITPN, especially the characteristics related to recurrence, have not been revealed. We performed a total remnant pancreatectomy for a patient whose ITPN recurred 16 months after pancreatoduodenectomy (PD). We report useful findings to clarify how ITPN reoccurs based on this experience and previously reported cases. CASE PRESENTATION: A 61-year-old male patient was diagnosed with pancreatic cancer and underwent PD. However, a postoperative pathologic examination diagnosed ITPN with invasive cancer. After receiving adjuvant chemotherapy, he was hospitalized for pancreatitis 16 months after the operation. He was diagnosed as having recurrence near the pancreato-jejunal anastomosis based on detailed examinations and underwent a remnant total pancreatectomy. From the results of the histopathological examination, he was found to have a recurrence of ITPN as a polypoid mass without invasion distant from the surgical stump of the first operation. Furthermore, tumor cells floating in the main pancreatic duct distant from the main tumor were observed at three locations. REVIEW OF THE LITERATURE: Including our case, five cases of recurrence in the remnant pancreas after surgery for ITPN have been reported. Recurrence in the main pancreatic duct was observed in four of these five cases. The primary tumor, which recurred in the remnant pancreas after surgery, was characterized as being relatively small and less invasive; however, Ki-67 labeling index was high. In immunohistochemical examination, the expression of MUC6, which is not one of characteristics of ITPN, tended to be positive. CONCLUSION: In this case, tumor cells were floating inside the pancreatic duct at several locations. From the results of this case and a review of previous reports, the cause of ITPN recurrence in this case seemed to be due to tumor cells leaving the tumor and implanting into the pancreatic duct.

A case report of metastatic lung adenocarcinoma with long-term survival for over 11 years.

RATIONALE: This is the first known report in the English literature to describe a case of metastatic non-small cell lung cancer that has been controlled for >11 years. PATIENT CONCERNS: A 71-year-old man visited our hospital because of dry cough. DIAGNOSIS: Chest computed tomography revealed a tumor on the left lower lobe with pleural effusion, and thoracic puncture cytology indicated lung adenocarcinoma. INTERVENTIONS: Four cycles of carboplatin and docetaxel chemotherapy reduced the size of the tumor; however, it increased in size after 8 months, and re-challenge chemotherapy (RC) with the same drugs was performed. Repeated RC controlled disease activity for 6 years. After the patient failed to respond to RC, erlotinib was administered for 3 years while repeating a treatment holiday to reduce side effects. The disease progressed, and epidermal growth factor receptor (EGFR) gene mutation analysis of cells from the pleural effusion detected the T790 M mutation. Therefore, osimertinib was administered, which has been effective for >1 year. OUTCOMES: The patient has survived for >11 years since the diagnosis of lung cancer. LESSONS: Long-term survival may be implemented by actively repeating cytotoxic chemotherapy and EGFR-tyrosine kinase inhibitor administration.

A Case of Influenza B and Mycoplasma pneumoniae Coinfection in an Adult.

A 19-year-old woman was referred to our hospital because of a persistent fever and cough that lasted for over a week. Influenza B virus infection was diagnosed using the rapid test kit. Initially, the patient was diagnosed with influenza B infection associated with lobar pneumonia and treated with an anti-influenza virus drug and sulbactam/ampicillin. The patient's fever persisted, and her respiratory condition worsened. On day 5, a computed tomography (CT) scan revealed an extension of the consolidation areas in the left lung and new opacities in the right lung. The antibiotic treatment was changed to meropenem and levofloxacin, and the patient's physical condition gradually improved. A sputum sample revealed the presence of Mycoplasma pneumoniae-specific DNA. Both influenza B virus and M. pneumoniae infections were confirmed serologically. This was a case of coinfection with influenza B virus and M. pneumoniae in a healthy young woman. The M. pneumoniae pneumonia diagnosis was delayed because the predominant feature observed in the CT scan was dense consolidation. M. pneumoniae should be considered as one of the causative pathogens in influenza coinfection cases with CT scan images presenting dense consolidation.

[Complete response achieved in a case of gastric gastrointestinal stromal tumor by administration of imatinib mesilate with concurrent relatively high-dose steroid therapy to control side effects].

We present a 53-year-old man who underwent proximal gastrectomy for gastric gastrointestinal stromal tumor (GIST) in August 2005. Imatinib mesilate (imatinib) 400 mg/day was started in February 2006 for left adrenal metastasis. Tumor size markedly decreased by April 2006, but medication had to be discontinued due to a pruritic rash. A distal pancreatectomy, splenectomy, and left adrenectomy were performed in August for recurrent adrenal metastases. Imatinib 200 mg/day started postoperatively was discontinued immediately due to fever and pruritus. Local recurrence with peritoneal dissemination was found in February 2007. Imatinib 100 mg/day with prednisolone (PDL) 5 mg/day was discontinued in two days due to pruritic dermatitis. Imatinib 200 mg/day with PDL 40 mg/day was restarted in April due to an increase in tumor size. Treatment continued without obvious side effects, and PDL dosage was tapered to 10 mg/day. The tumor was no longer visible on CT in May 2008, and complete response is being maintained as of August 2009.