Background: Copy number variation (CNV) is associated with progression of esophageal cancer (EC), a common gastrointestinal neoplasm. Methods: Using sequencing data, CNV data, and clinical data of EC transcriptome samples obtained from public databases, we performed differential expression analysis on sequencing data. Differentially expressed CNV-driven lncRNAs were screened using the chi-square test, and CNV-driven lncRNA-associated miRNAs and mRNAs were predicted. Cytoscape software was then used to construct ceRNA networks. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed to investigate biological functions of mRNAs in the ceRNA network. Survival curves were plotted to explore correlations between lncRNAs in the ceRNA network and overall survival of CNV patients. Multiple databases were used to predict lncRNAs-related drugs. Results: A dysregulated lncRNA-associated ceRNA network driven by CNV in EC, including 11 lncRNAs, 11 miRNAs and 159 mRNAs, was constructed. Downstream enrichment of mRNAs was related to biological processes such as extracellular matrix organization, indicating that these mRNAs mainly participate in intercellular exchange between tumor cells. Additionally, expression of all lncRNAs in the ceRNA network, except LINC00950, LINC01270 and MIR181A1HG, was correlated with patients' CNV. In addition, none of the 11 lncRNAs was significantly correlated with overall survival of CNV patients. CH5424802 and PD-033299CNV mainly affected the RTK signaling pathway and the cell cycle of tumor cells via RP11-180N14.1 and RP11-273 G15.2 in the ceRNA network. Conclusions: This study identified 11 CNV-driven lncRNAs that might affect EC development, 2 of which have promising effects if applied to drug treatment. These findings might assist in identifying novel treatments for EC.

Background: Opioid-induced respiratory depression (RD) is a potentially life-threatening adverse drug event. This study used the Japanese Adverse Drug Event Report (JADER) database to investigate the profile of opioid-related RD in non-cancer patients. Methods: We analyzed data recorded in the JADER database between April 2004 and February 2020, which were downloaded from the Pharmaceutical and Medical Devices Agency website. Reporting odds ratios for RD were calculated for the 20 opioids approved in Japan, and daily dose and onset time were further analyzed for opioids used in chronic non-cancer pain (CNCP). Results: Among the opioids, RD adverse event signals were detected for 22 combinations of opioids and administration routes in non-cancer patients. Of these combinations, transdermal buprenorphine and oral tramadol/acetaminophen were approved for CNCP and tended to be reported more frequently in elderly patients. The median daily doses of transdermal buprenorphine and oral tramadol/acetaminophen were 10.0 and 22.5 mg of daily oral morphine equivalent doses, respectively, which are within the standard range for starting dosage. The median time-to-onset of transdermal buprenorphine and oral tramadol/acetaminophen was 6.5 and 4.0 days, respectively, and 75% of cases were reported within 20 to 40 days after the start of treatment. The hazard type for both opioids was classified as early failure. Conclusions: Our findings suggest that elderly CNCP patients should be closely monitored after the start of opioid treatment, especially during the first week and, if possible, for 1 month, even if starting doses are within ranges recommended by the manufacturer and guidelines.

Background: As members of a medical team, pharmacists are expected to provide optimal patient-centered, evidence-based pharmacotherapy. In Japan, in consideration of the importance of palliative care, a system was initiated for certifying palliative care pharmacists in 2010. However, no studies have evaluated the usefulness of board certification in palliative pharmacy. Therefore, we surveyed the status of medication guidance for the physical and psychological symptoms of patients receiving palliative care and compared the medication guidance provided by certified and uncertified pharmacists. Methods: The survey was conducted in February and March 2022. Pharmacists registered as members of the Japanese Society of Pharmaceutical Palliative Care and Sciences were surveyed by using a web-based questionnaire and 209 pharmacists responded: the certified pharmacist group comprised 123 (58.9%) pharmacists and the uncertified pharmacist group comprised 86 (41.1%) pharmacists. Results: The certified pharmacist group provided better and more frequent medication guidance, according to responses to four of the six items related to pain relief. Three items were related to non-pain symptom relief, and one of the four items was related to psychiatric symptom relief (P < 0.05). The study showed that the certified pharmacist group received a better rating than the uncertified pharmacist group for involvement in palliative pharmacotherapy leading to improvement of patient quality of life (P < 0.05). Conclusion: As compared with uncertified pharmacists, certified pharmacists intervened more proactively and provided a broader range of palliative care.

Parathyroid tumors (PTs) are sometimes difficult to diagnose because they are small and have low-velocity blood flow, which can be missed by current imaging modalities. PTs consist of parathyroid adenoma (PA), parathyroid cyst, and parathyroid carcinoma (PC). Detective flow imaging (DFI) is a new imaging technology that displays low-velocity blood flow. Herein, we report two cases in which DFI was useful for diagnosis of PTs. One patient had a PA and a parathyroid cyst in close proximity, and the other had a PC. To our knowledge, this is the first report to demonstrate the usefulness of DFI in the diagnosis of PTs.

A 79-year-old woman collided with a cliff in a passenger automobile. The fire department acknowledged an automated collision notification from the D-Call Net (DCN) at 1 min after the accident and called for doctors by helicopter ( "Doctor-Heli" [DH] in Japan) 9 min after the injury. The DH reached the victim 28 min after the injury, and examination revealed pain in the right side of her chest, tachypnea, and a weak radial artery pulse (indicating shock). The DH arrived at the hospital 49 min after the injury. Thoracic drainage was performed for right-sided tension pneumothorax. She recovered from shock but was diagnosed with flail chest and placed on a respirator. She was extubated on postoperative day 6 and transferred to a rehabilitation hospital on postoperative day 57. Because of the DCN, the patient received treatment 15 min earlier than she would have with the conventional system. Emergency response task forces must develop strategies for connecting DCN warnings to rapid medical response systems.

Our case involved a 66-year-old woman who noticed progressive asymmetric involuntary movement, difficulty speaking, and difficulty swallowing. The patient fractured her femur due to a lower extremity involuntary movement while walking. During the course of her treatment for the fracture, her neurological symptoms worsened. Approximately 2 months after becoming aware of her symptoms, she visited our clinic for evaluation of difficulty with unassisted walking and weight loss due to dysphagia. To identify the cause of her neurological symptoms, hematological examination, brain magnetic resonance imaging, single-photon emission computed tomography for cerebral blood flow, electroencephalography, and a somatosensory evoked potential test were conducted. Although the cause of her neurological symptoms could not be determined, computed tomography revealed the presence of breast cancer, which led us to suspect paraneoplastic neurological syndrome (PNS). After breast cancer treatment, her neurological symptoms improved simultaneously. Therefore, the patient was retrospectively diagnosed with PNS. We report a case of PNS whose neurological symptoms followed a subacute course and were relieved after breast cancer treatment.

Acquired hemophilia A (AHA) is a rare disease in which an autoantibody causes bleeding by interacting with and inhibiting the coagulation activity of endogenous factor VIII (FVIII). Most cases of AHA are idiopathic; known causes include autoimmune diseases, malignant tumors, pregnancy, drugs, and viral infections. An 86-year-old man was diagnosed with AHA based on the following results: an activated partial thromboplastin time (aPTT) extension of 130.7 seconds, presence of an inhibitor pattern in a mixing study, an endogenous factor VIII (FVIII) level of <1%, and an FVIII inhibitor titer of >5.1 Bethesda units (BU). The activity of von Willebrand factor (vWF) was diminished (<10%), which was considered a complication of acquired von Willebrand syndrome (AVWS). The patient was started on prednisolone, and the inhibitor level eventually became negative. vWF values also became normal. However, 1 year later, he was hospitalized for treatment of coronavirus disease 2019 (COVID-19). Blood testing showed an aPTT extension of 110.5 seconds, FVIII level of 4%, and FVIII inhibitor titer of 0.8 BU; thus, a relapse of AHA was diagnosed. After administration of corticosteroid and remdesivir, he recovered from COVID-19 and AHA. The inhibitor level became negative on the 9th day of admission. Several studies have implicated COVID-19 infection and vaccination in AHA. We recommend that aPTT be measured when patients with AHA are infected with SARS-CoV2, to confirm AHA relapse.

Tumor necrosis factor (TNF) inhibitors, including adalimumab, are widely used to treat refractory psoriatic arthritis (PsA). Although isoniazid chemoprophylaxis is generally effective in preventing reactivation of latent tuberculosis infection (LTBI), prophylactic measures do not fully protect against development of active tuberculosis. We report a rare case of active tuberculosis despite chemoprophylaxis for LTBI in a patient receiving adalimumab for PsA. A 60-year-old Japanese woman who had received a diagnosis of psoriasis at age 35 years presented with arthralgia of the right hand, which she first noticed 2 months previously. Physical examination showed scattered erythematous papules and plaques with scales on her trunk, extremities, and scalp. Her right metacarpophalangeal and proximal interphalangeal joints were swollen and painful, and her right wrist and elbow were painful. PsA was diagnosed and adalimumab was initiated. Because an interferon-γ release assay (IGRA) showed a borderline result at screening, isoniazid was administered as chemoprophylaxis for LTBI. At 22 months after initiation of adalimumab, IGRA was positive and chest CT disclosed centrilobular nodules in both lungs and swelling of multiple lymph nodes. Culture of sputum at 24 months demonstrated Mycobacterium tuberculosis. Active tuberculosis was diagnosed, and treatment with a combination of isoniazid, rifampicin, ethambutol hydrochloride, and pyrazinamide was started. To ensure timely diagnosis and treatment of active tuberculosis, a tuberculosis expert should be consulted at an early stage, with regular screening and monitoring.