Objective To identify the risk factors for severe diverticular bleeding in an elderly population.

Methods Using a comprehensive computerized hospital database, severe and non-severe diverticular bleeding cases were compared for 19 factors: the age, sex, body mass index, comorbid conditions (hypertension, cardiovascular disease, cerebrovascular disease, and chronic renal failure, including those undergoing dialysis), history of diverticular bleeding, use of low-dose aspirin, use of antiplatelet agent besides aspirin, use of anticoagulant agent, use of prednisolone, use of non-steroidal anti-inflammatory drugs, use of cyclooxygenase-2 selective inhibitors, changes in vital signs, hypoalbuminemia, bilateral diverticula, identification of bleeding lesion, and rebleeding. Severe bleeding was defined as the need for blood transfusion, emergency surgery, or vascular embolization.

Patients A total of 258 patients were admitted for lower gastrointestinal bleeding between August 2010 and July 2020, among whom 120 patients over 65 years old diagnosed with diverticular bleeding were included in this study.

Results Fifty-one patients (43%) had severe diverticular bleeding. Independent risk factors for severe diverticular bleeding were as follows: change in vital signs [odds ratio (OR), 5.23; 95% confidence interval (CI), 1.9-14.4; p=0.0014], hypoalbuminemia (OR, 12.3; 95% CI, 1.97-77.3; p=0.0073), bilateral diverticula (OR, 3.47; 95% CI, 1.33-9.02; p=0.011), and rebleeding (OR, 5.92; 95% CI, 2.21-15.8; p<0.001). The area under the receiver operating characteristic curve was 0.79 after cross validation.

Conclusion Severe diverticular bleeding in elderly population may be predicted by changes in their vital signs, hypoalbuminemia, bilateral diverticula, and rebleeding.

Objective S-1 and modified FOLFIRINOX (mFFX) were often used as the second-line chemotherapies after failure of gemcitabine plus nab-paclitaxel (GnP) in unresectable pancreatic cancer (UPC) until nanoliposomal irinotecan plus 5-fluorouracil/leucovorin therapy was approved as an alternative in Japan in 2020. However, the clinical outcomes of S-1 and mFFX after GnP have scarcely been reported. Therefore, we retrospectively studied them.

Methods We extracted the clinical data of 86 patients with UPC who received second-line chemotherapy after GnP between 2015 and 2020. Among the patients who had a good organ functions and no massive ascites, 41 patients treated with S-1 and 21 treated with mFFX were enrolled.

Results Compared to S-1, mFFX tended to be used for younger patients with a good general condition (median age, 63 vs. 71 years, p<0.01; and performance status 0, 67% vs. 37%, p<0.05). The median progression-free and overall survival were similar between the S-1 (3.7 and 7.2 months, respectively) and mFFX (3.3 and 7.4 months, respectively) groups. The response rate in patients with measurable lesions was 4% (n=1/23) in the S-1 group and 17% (n=2/12) in the mFFX group. The incidence of grade 3 or 4 adverse events was 20% in the S-1 group and 57% (neutrophil count decreased in 43%) in the mFFX group (p<0.01).

Conclusion S-1 and mFFX were both acceptable second-line chemotherapies after GnP therapy for UPC, although attention should be paid to myelosuppression during mFFX treatment. Further studies involving nanoliposomal irinotecan plus 5-fluorouracil/leucovorin therapy are necessary to facilitate the selection of the optimal regimen for each patient.

Objective Dasatinib, a second-generation tyrosine kinase inhibitor, is used for chronic myelogenous leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). It reportedly causes pulmonary arterial hypertension (PAH) and the dose-dependent induction of apoptosis in pulmonary endothelial cells. However, no report has yet discussed the relationship between dasatinib-induced PAH and drug dose. We therefore investigated the incidence of dasatinib-induced PAH and the relationship between dasatinib-PAH and drug dose in consecutive patients with CML and Ph+ ALL who took dasatinib.

Methods The clinical data of 128 patients with CML (94 patients) and Ph+ ALL (34 patients) were retrospectively analyzed.

Patients All patients (>17 years old) who received dasatinib from January 2009 to March 2020 at Jichi Medical University (Tochigi, Japan) were included. Patients who transferred within one month of starting dasatinib administration were excluded.

Results Four (4.3%) and three (8.8%) patients developed pulmonary hypertension (PH), which was considered present when the transtricuspid pressure gradient was ≥40 mmHg, in the CML and ALL groups, respectively. No significant difference was observed between the PH onset and the administration period, cumulative dose, or daily dose of dasatinib. PH occurred in seven patients (5.5%), and the period from the start of dasatinib administration to the PH onset ranged from 7 to 39 (median: 28) months. No patients died from PH in either group.

Conclusion Dasatinib-induced PAH does not occur time- or dose-dependently. When administering dasatinib, cardiovascular diagnostic modalities should be routinely checked, and PAH occurrence should be promptly detected.

Objective The coronavirus disease 2019 (COVID-19) pandemic continues to spread across the world, and the utility of many drugs for treatment has been suggested. However, few studies have examined the efficacy and safety of treatment with baricitinib, remdesivir, and dexamethasone.

Methods A retrospective, cohort study of patients who were admitted to Kurashiki Central Hospital in Japan between April 6 and June 29, 2021, was conducted. Differences in patients' background characteristics, clinical outcomes, and safety were investigated in the groups with and without baricitinib treatment. The primary outcome was the bacterial infection rate, and the secondary outcome was the 28-day mortality rate. An inverse probability of treatment weighting (IPTW) analysis, including 12 covariates, was used as a propensity score analysis to reduce biases.

Results In total, there were 96 patients, including 43 in the baricitinib-containing therapy (BCT) group and 53 in the non-baricitinib-containing therapy (non-BCT) group. In the BCT group, the ordinal scale on admission was 2.3% with 4, 51.1% with 5, 23.3% with 6, and 23.3% with 7. In the non-BCT group, the ordinal scale was 1.9% with 3, 18.9% with 4, 58.5% with 5, 13.2% with 6, and 7.5% with 7. After adjusting by the IPTW analysis, the BCT group did not have an increased bacterial infection rate [odds ratio (OR), 1.1; 95% confidence interval (CI), 0.36-3.38; p=0.87] or 28-day mortality rate (OR, 0.31; 95% CI, 0.07-1.3; p=0.11) compared with the non-BCT group.

Conclusion BCT can be administered without increasing the infection risk compared with non-BCT.

Objective In myotonic dystrophy type 1 (DM1), the CTG repeat size in the dystrophia myotonica protein kinase gene has been shown to correlate with disease severity and is a potential predictive marker for respiratory decline. However, genetic testing can be challenging in some clinical situations. We developed a simple formula for estimating the CTG repeat size using a single spirometry test in patients with DM1.

Methods In this single-center retrospective study, we reviewed 50 consecutive patients with genetically confirmed DM1 whose follow-up visits were at our hospital. The patients were randomly assigned to training and test analysis subsets. By applying a linear mixed model to the longitudinal spirometry results of the training set, we calculated the fixed effects on the annual respiratory decline. Subsequently, we derived a prediction formula to calculate the repeat size that incorporated %vital capacity (%VC) and the patient's age at the time of the spirometry evaluation; the results were validated by the test set.

Results A total of 157 spirometry tests were recorded. The fixed effects on the annual %VC decline were =-0.90. The derived formula [repeat size=-16.8× (age+%VC/0.90) +2663] had a moderate predictive performance with a mean coefficient of determination of 0.41.

Conclusion The CTG repeat size in patients with DM1 can be potentially predicted using a simple formula based on a single spirometry test conducted at any time over the disease course. It can be useful as a supportive tool for advance care planning when genetic testing is not available.

Objective To investigate seizure control in patients with epilepsy during the coronavirus disease 2019 (COVID-19) pandemic.

Method A systematic review and meta-analysis was conducted, and the MEDLINE, EMBASE, CENTRAL, and ClinicalTrials.gov databases were comprehensively searched for relevant studies. Studies that reported seizure control in patients with epilepsy during the COVID-19 pandemic were included. Pooled proportions with 95% confidence intervals (CIs) of patients with epilepsy who experienced seizure worsening during the COVID-19 pandemic were assessed using a random-effects model. The quality of the assessment for each study, heterogeneity between the studies, and publication bias were also evaluated. Subgroup analyses were performed, excluding studies with reports of seizures worsening from caregivers.

Results A total of 24 studies with 6,492 patients/caregivers were included in the meta-analysis. The pooled proportion of seizure worsening was 18.5% (95% CI: 13.9-23.6; I²=96%; p<0.01). The pooled proportion of seizure worsening in the subgroup analysis was 18.9% (95% CI: 13.5-25.0; I²=96%; p<0.01).

Conclusion Although the heterogeneity was high, our results showed a relatively high incidence of seizure worsening during the COVID-19 pandemic. During the COVID-19 pandemic, physicians should be aware of the likelihood of worsening seizures in patients with epilepsy.

Objective Vaccination technique is a crucial skill for medical trainees to learn, especially in the current coronavirus disease 2019 pandemic. To this end, validated assessment tools are essential in teaching appropriate techniques. However, valid instruments for assessing vaccine administration skills have not yet been developed. We therefore explored the development and validation of an assessment tool for vaccination techniques based on expert consensus.

Methods We implemented a modified Delphi process to develop a vaccination technique assessment tool. We then conducted a validation study to establish the reliability and validity of the tool.

Results Two rounds of the modified Delphi process were performed to generate a 19-item, vaccination performance assessment checklist. In the validation study, the linear weighted kappa value for inter-rater reliability of the overall checklist score was 0.725. Spearman's correlation coefficient between the mean checklist score and the global rating was 0.98 (p<0.01).

Conclusions This is a pioneering study examining the development and validation of an assessment tool for vaccine administration techniques. The tool will be widely used in vaccination-related education.

We herein report two patients with hepatocellular carcinoma (HCC) who exhibited intraabdominal bleeding caused by tumor rupture soon after lenvatinib initiation. A hypervascular nodule was present in the lateral segment manifesting extrahepatic protrusion in an 81-year-old-man and in the caudate lobe, which was completely occupied by the tumor, in an 83-year-old-man. Both patients were given lenvatinib, and epigastralgia occurred suddenly three and five days later. Computed tomography revealed high-attenuation areas suggesting bleeding around the left and caudate lobes. Considering the strong antiangiogenic effects by lenvatinib, transcatheter arterial embolization should be performed before lenvatinib initiation in patients with subcapsular HCC.

An elderly patient was admitted to our hospital for acute heart failure soon after receiving influenza vaccination. On admission, chest radiography revealed pulmonary edema. An electrocardiogram showed poor R progression, and echocardiography showed diffuse hypokinesis and myocardial edema. The serum troponin level was elevated. A histopathological evaluation indicated active myocarditis with lymphocyte-predominant infiltrates. A drug-induced lymphocyte stimulation test (DLST) was positive. The patient rapidly recovered from heart failure after treatment with conventional heart failure drugs, such as intravenous diuretics and vasodilators. These experimental data and the clinical course suggest that influenza vaccination was responsible for heart failure due to acute lymphocyte myocarditis.

An 84-year-old woman presented with dyspnea in the sitting position. Platypnea-orthodeoxia syndrome (POS) was suspected based on arterial desaturation when her posture changed from the supine to the sitting position. Transesophageal echocardiography showed right-to-left shunting enhancement through a patent foramen ovale (PFO) in the sitting position. Three-dimensional (3D) cardiac CT in the sitting position revealed that the elongated ascending aorta compressed the right ventricular inflow tract, resulting in restricted blood flow to the right ventricle and increased right-to-left shunting. This case highlights the role of 3D-CT in the sitting position in the management of POS.

A 60-year-old Japanese woman was hospitalized for cardiogenic shock 24 days after receiving the second dose of the coronavirus disease 2019 BNT162b2 vaccine. Impella CP left ventricular assist device implantation and venoarterial peripheral extracorporeal membranous oxygenation were immediately initiated along with inotropic support and steroid pulse therapy, as an endomyocardial biopsy specimen showed myocarditis. Three weeks later, her cardiac function had recovered, and she was discharged. An immune response associated with the presence of spike protein in cardiac myocytes may be related to myocarditis in the present case because of positive immunostaining for severe acute respiratory syndrome coronavirus 2 spike protein and C4d in the myocardium.

A 41-year-old Japanese man was admitted to our hospital with acute perimyocarditis 4 weeks after coronavirus disease 2019 (COVID-19) infection. Ten days after admission, the patient showed bilateral facial nerve palsy in the course of improvement of perimyocarditis under treatment with aspirin and colchicine. After prednisolone therapy, perimyocarditis completely improved, and the facial nerve palsy gradually improved. Acute perimyocarditis and facial nerve palsy can occur even 4 weeks after contracting COVID-19.

Metformin-associated lactic acidosis (MALA) is an extremely rare but life-threatening adverse effect of metformin treatment. The lifestyle changes associated with the coronavirus disease 2019 (COVID-19) pandemic may increase the potential risk of MALA development in patients with diabetes. We herein report a 64-year-old Japanese man taking a small dose of metformin who presented with MALA accompanied by hypoglycemia secondary to increased alcohol consumption triggered by lifestyle changes during the pandemic. Physicians should prescribe metformin judiciously to prevent MALA development and pay close attention to lifestyle changes in patients at risk for MALA during the COVID-19 pandemic.

A 57-year-old man with lung adenocarcinoma was treated with chemotherapy and immune checkpoint blockade. After two cycles of carboplatin, pemetrexed, and pembrolizumab, he developed a persistent fever. Chest computed tomography (CT) suggested inflammation of the aortic wall. We treated the patient with corticosteroids. After four cycles of carboplatin, pemetrexed, and pembrolizumab, chest CT showed an aneurysm in the ascending aorta. We diagnosed him with inflammatory thoracic aortic aneurysm induced by pembrolizumab and performed surgical replacement of the ascending aorta. Although this might be a very rare case, we should be aware of aortitis as a potential adverse effect of pembrolizumab.

Unilateral absence of the pulmonary artery (UAPA) with or without other anomalies in the heart is a rare congenital malformation. A 55-year-old Filipino woman without a remarkable medical history was admitted to our hospital for hemoptysis. Contrast-enhanced chest computed tomography revealed the absence of the left pulmonary artery. Echocardiography and right heart catheterization showed no cardiac malformations or pulmonary hypertension. We diagnosed her with isolated left-sided UAPA and performed transarterial embolization of the left inferior phrenic artery. This resolved the hemoptysis, and there was no recurrence during the four-year follow-up period.

We herein report a 44-year-old Japanese man with hereditary transthyretin amyloidosis (ATTRv amyloidosis) harboring the variant Leu58Arg (p.Leu78Arg) in TTR in whom we conducted an observational study with liver transplantation (LT) and transthyretin (TTR) stabilizers (tafamidis and diflunisal) for 9 years. This patient showed gradual deterioration of sensory, motor, and autonomic neuropathy symptoms after LT. Furthermore, cardiac amyloidosis gradually developed. Although the present case showed deterioration of the symptoms after disease-modifying treatments, LT might be suitable in patients with the same variant if they are young and in good condition due to a long survival after LT.

We herein report the first case of occipital neuralgia secondary to spinal cord infarction. A 74-year-old woman suddenly developed numbness and dysmetria in her right arm. Two days later, she developed a paroxysmal shooting pain in the right posterior part of the scalp three to five times per day. Magnetic resonance imaging revealed a hyperintense lesion in the right posterior column and dorsal root entry zone at the C2 level. The patient was subsequently diagnosed with occipital neuralgia secondary to spinal cord infarction. Diverse etiologies need to be considered in occipital neuralgia secondary to spinal cord lesions.

KMT2B-related dystonia (DYT28, DYT-KMT2B) is an inherited dystonia that generally begins in the lower limbs during childhood and evolves into generalized dystonia. We herein report a case of adult-onset DYT28 with dystonic tremor. A 27-year-old woman initially displayed right upper limb and cervical tremors over the course of 1 year. A neurological examination also revealed cervical and lower limb dystonia. Although the disease generally develops during childhood, we diagnosed the woman with DYT28, as genetic testing revealed a mutation in KMT2B. Adult-onset patients with DYT28 might also show uncommon symptoms as well as DYT-TOR1A (DYT1).

A 72-year-old woman presented with acute-progressive muscle weakness after a rash in the left upper limb. Muscle weakness was restricted to the left C5 innervated muscles. Short inversion time inversion recovery magnetic resonance imaging (MRI) showed a high-intensity signal in the left C5 nerve root, and nerve ultrasound showed its enlargement. She was diagnosed with segmental zoster paralysis (SZP) and treated with acyclovir and methylprednisolone. Her muscle strength gradually recovered, and the abnormal signal and enlargement in the left C5 nerve root improved. This is the first SZP case of confirmed improvement of abnormal findings on MRI and nerve ultrasound in association with muscle power recovery.

Ankylosing spondylitis (AS) is rarely accompanied by other autoimmune diseases and/or hematologic disorders. We herein report a 46-year-old man with AS coexisting with relapsing polychondritis (RP), antiphospholipid syndrome (APS) and myelodysplastic syndrome (MDS). While receiving anti-TNF therapy for AS, the patient developed anemia and was diagnosed with MDS. After six months, he developed swelling and redness of the nose and both auricles. RP was diagnosed by an ear biopsy. Afterward, during the evaluation of a repeated fever, APS was diagnosed. This case of AS with multiple autoimmune diseases and hematologic malignancy successfully responded to a Janus kinase inhibitor (baricitinib).

A 70-year-old healthy woman came to our hospital with right index finger pain and swelling after an injury incurred due to a commercial dishwasher. X-ray of the hand showed osteolysis around the distal interphalangeal joint. A further examination revealed Pseudomonas aeruginosa in the unexposed pus, so the patient was treated with a total of 10 weeks of cefepime, followed by levofloxacin and debridement twice. While this may have been a case of bacterial replacement, we should still consider P. aeruginosa infection in healthy adults when faced with an episode of waterborne injury.

Disseminated nontuberculous mycobacterial infection (DNTM) is typically observed in immunocompromised hosts. Recently, it has been reported that healthy individuals with serum neutralizing autoantibodies for interferon (IFN)-γ can also develop DNTM. We herein report a case of anti-IFN-γ antibody-seropositive DNTM caused by Mycobacterium kansasii with symptoms mimicking TAFRO or POEMS syndrome, including anasarca, organomegaly, skin pigmentation, polyneuropathy, osteosclerotic change, thrombocytopenia, serum M protein, high C-reactive protein level, and reticulin fibrosis. The combination of antimicrobial chemotherapy with glucocorticoid and intravenous immunoglobulin improved his symptoms. Glucocorticoids may be an effective method of suppressing the production of anti-IFN-γ antibodies in DNTM.

A 66-year-old woman underwent partial mastectomy and a sentinel lymph node biopsy for left breast cancer; the pathological diagnosis was invasive ductal carcinoma (pT1aN0, pStage I, triple-negative subtype). Postoperative radiotherapy was performed. Two years later, she developed redness and induration at both breasts. The diagnosis was bilateral inflammatory breast cancer. After four cycles of dose-dense epirubicin and cyclophosphamide followed by 12 weekly paclitaxel cycles, bilateral total mastectomy and axillary lymph node dissection were performed. At the one-year follow-up after undergoing operation and radiotherapy, she remained alive without recurrence. Dose-dense treatment regimens may help patients achieve complete resection without short-term recurrence.