地方独立行政法人　総合病院国保旭中央病院 研修医・レジデント

次の各問いに対する答えを解答用紙に記入しなさい。

Ⅰ．老化に関する以下の文章を和訳しなさい。

Aging is a major risk factor for the higher incidence and prevalence of chronic conditions, such as cardiovascular diseases, metabolic diseases, and neurodegenerative diseases. Chronic systemic sterile inflammation is crucially involved with the etiology and progression of these conditions. Several features of premature aging have been reported in young adults or adults with these chronic conditions. In the elderly, these conditions are often presented with multimorbidity and may finally lead to organ failure and death. With the advance of immunosenescence (aging of the immune system), older adults also become more susceptible to infectious diseases and cancer. Elderly population is at increased risk for developing and dying from influenza and coronavirus disease 2019 (COVID-19). Of note, the adults with chronic (inflammatory) conditions are the ones with heightened risk for developing severe COVID-19 and dying. Therefore, there is an interplay between immunosenescence and age-related diseases. In this way, it is important to intervene more quickly and multidimensionally with novel preventive and therapeutic approaches. First of all, it is important to differentiate acute from chronic inflammatory processes. Acute inflammation is a transient and useful process aiming the elimination of pathogens and tissue regeneration, orchestrated by cells of the innate immunity. But aging starts a chronic inflammatory process, known as "inflammaging", with persistent and non-resolved production of pro-inflammatory mediators (cytokines, chemokines, and acute phase proteins) that increases the risk for age-related morbidity and mortality. Some lifestyle factors, including smoking, obesity, and lack of exercise, are known to be associated with persistent inflammation. Although there are many sources of inflammaging, some evidence indicates the presence of overt infections during life to fuel inflammaging.

Ⅱ．機能性僧帽弁閉鎖不全症に関する以下の文章を和訳しなさい。

Our understanding of mitral regurgitation (MR) has grown exponentially in the past few years: We have moved beyond primary MR due to mitral valve prolapse to a recognition that secondary MR, detected more commonly now with increasing prevalence in heart failure as well as widespread imaging, is not just MR with nonprolapsing leaflets, but an entirely different entity with multiple new subtypes with diverse pathophysiology. Functional MR (FMR) is a complex problem with both diagnostic and therapeutic challenges and adverse prognostic impact. Classic FMR is caused by left ventricular (LV) dysfunction; atrial FMR occurs when left atrial dilation results in mitral annular dilation in the absence of LV dysfunction. In classic FMR, normal mitral leaflets are prevented from closing properly by a combination of decreased closing force and outward expansion of the papillary muscles and their supporting LV myocardium. This can occur with small regional wall motion abnormalities or with global LV dilation and can occur in both ischemic and nonischemic cardiomyopathy. Recent evidence implicates newer mechanisms, including significant myocardial fibrosis/scar as an important factor that contributes to the adverse prognosis of FMR and papillary muscle dyssynchrony.

次の各問いに対する答えを解答用紙に記入しなさい。

Ⅰ．急性腸閉塞に関する以下の文章を和訳しなさい。

Distention of the intestine is caused by the accumulation of gas and fluid proximal to and within the obstructed segment. Between 70 and 80% of intestinal gas consists of swallowed air, and because this is composed mainly of nitrogen, which is poorly absorbed from the intestinal lumen, removal of air by continuous gastric suction is a useful adjunct in the treatment of intestinal distention. The accumulation of fluid proximal to the obstructing mechanism results not only from ingested fluid, swallowed saliva, gastric juice, and biliary and pancreatic secretions but also from interference with normal sodium and water transport. During the first 12-24 h of obstruction, a marked depression of flux from lumen to blood of sodium and water occurs in the distended proximal intestine. After 24 h, sodium and water move into the lumen, contributing further to the distention and fluid losses. Intraluminal pressure rises from a normal of 2-4 cmH2O to 8-10 cmH2O. The loss of fluids and electrolytes may be extreme, and unless replacement is prompt, hypovolemia, renal insufficiency, and shock may result. Vomiting, accumulation of fluids within the lumen, and the sequestration of fluid into the edematous intestinal wall and peritoneal cavity as a result of impairment of venous return from the intestine all contribute to massive loss of fluid and electrolytes.

Ⅱ．COVID-19 に対する呼吸機能検査実施に関する以下の文章を和訳しなさい。

Consideration #1: Understand the prevalence of COVID19 in your community.
In high prevalence communities, spirometry testing must be restricted, and spirometry testing should only be done if absolutely necessary. In low prevalence communities, a negative COVID19 test done 48 hours before the procedure is more reliable because there are fewer false negative individuals in the community. In these low prevalence communities, spirometry may be less restrictive.
Consideration #2: Weight the risks and benefits of spirometry. Only perform spirometry tests that are essential.
Examples of essential spirometry tests may include preoperative risk stratification, diagnosis of dyspnea, monitoring patients at risk for drug-related pulmonary toxicity, monitoring lung transplant patients, and accurate diagnosis of asthma or COPD.
Consideration #3: Screen the patient before the spirometry test.
1. Screen patients and caregivers telephonically or through the EMR for COVID19 symptoms, previous exposure, and prior COVID19 testing before arriving at the clinic.
2. Pre-screen patients as they arrive at the clinic, including taking their temperature and screening for potential COVID19 symptoms such as chills, cough, sore throat, shortness of breath/chest tightness, loss of taste or smell, runny nose, nasal congestion, headache, severe fatigue/exhaustion, and/or muscle pain.
Consideration #4: Follow appropriate precautions for both the patient and healthcare professional.
1. If a patient is showing flu-like symptoms or symptoms of COVID19 or is at high-risk for COVID19, postpone the spirometry test. COVID19 patients must not be tested for minimum of 30 days post infection.
2. While in the clinic, all patients should wear a face mask.
3. Maintain a minimum of six feet between patients.
4. Family members and friends should not accompany the patient inside the clinic, except for one caregiver of minors or disabled individuals.

次の各問いに対する答えを解答用紙に記入しなさい。

Ⅰ．乳がんと関節リウマチに関する以下の文章を和訳しなさい。

With a lifetime risk of close to 1 in 10, breast cancer is the most common cancer among women. Rheumatoid arthritis (RA) is the most common rheumatic disease affecting the joints, and has a marked female predominance. Although the overall risk of malignancies in RA is increased by 10%–15% compared with the general population, large cohort studies have consistently reported decreased occurrence of breast cancer among women with RA. The characteristics and the reason(s) behind the decreased risk of breast cancer in women with RA remain unknown, indeed also virtually unstudied. Hormonal factors such as hormone replacement therapy (HRT), early menarche and late menopause, no breast feeding and nulliparity and increasing age at first birth are all established risk factors for breast cancer. The role of these factors in the occurrence of RA is less clear. For HRT, available evidence does not indicate an association with risk of RA. For breast feeding, studies to date have reported a protective effect against RA, while results for parity and risk of RA are inconclusive. Early menopause may be associated with subsequent development of RA. Importantly, however, no study has assessed the extent to which the decrease in risk of breast cancer in women with RA can be explained by known breast cancer risk factors. If the observed reduction in the risk of breast cancer in women with RA was attributable to shared risk factors rather than a causal effect of the RA disease or its treatment, then one would expect that the reduced risk of breast cancer would be present already before the onset of RA.

Ⅱ．心臓と腎臓の相互依存に関する以下の文章を和訳しなさい。

The heart and the kidney are interlinked in physiologic states to maintain salt-water homeostasis and normal BP. In health, the crosstalk between the two organs helps the body to respond to changes in kidney perfusion resulting from volume depletion or overload, to maintain appropriate blood flow to vital organs and thereby avoid ischemia or hyperperfusion injury. In disease, the kidney and heart can adversely affect each other's function. On the one hand, inability to excrete salt and water and abnormal renin secretion by the diseased kidney increases cardiac preload, afterload, and heart failure; on the other hand, poor kidney perfusion owing to low cardiac output, and renal venous congestion owing to right heart failure, causes kidney failure. When both organs are diseased, they adversely affect each other's function, which poses significant challenges in the management of patients with compromised heart and kidney function. Common pathologic mechanisms may affect both organs and cause simultaneous dysfunction of the kidney and heart. The neurohumoral interactions between the two organs are complex in disease states. The natriuretic peptides, which induce diuresis with cardiac volume overload, are upregulated with kidney disease so as to help with associated fluid retention; however, they can be elevated because of poor elimination of the peptide molecules by the kidneys themselves. During treatment of heart failure with diuretics, although congestive symptoms and brain natriuretic peptide (BNP) concentrations improve, kidney function may worsen because of a reduction in kidney plasma flow. Stopping of diuretics may improve kidney function but worsen cardiac volumes and level of BNP.

次の各問いに対する答えを解答用紙に記入しなさい。

Ⅰ．COPD急性憎悪（AE）と末梢血好酸球数に関する以下の文章を和訳しなさい。

BACKGROUND: Characterizing acute exacerbations of COPD (AECOPD) and individualizing therapy is challenging. Key exacerbation therapies include antibiotics and systemic corticosteroids. Blood eosinophils, when either low or high, may offer a simple, inexpensive distinction to predict beneficial responses to these therapies.
METHODS: Exacerbations were grouped according to blood eosinophil count as low (<50/μL), normal (50-150/μL), or high (>150/μL). Exacerbations were classified as being associated with infection if either virus testing was positive or C-reactive protein was ≥20 mg/L. Associations of eosinophil groups with infection, hospital length or stay, and 12-month survival were compared using appropriate statistical methods.
RESULTS: There were no significant differences in baseline characteristics between patients with low, normal, or high blood eosinophils in either cohort. Eosinophil counts <50/μL were more strongly associated with infection (91% vs 51.9%, p = .001), distinguished patients with longer median hospital stays (7 vs 4 days, p < .001), and were associated with lower 12-month survival (82.4% vs 90.7%, p = .028; pooled data of both cohorts) than eosinophil counts > 150/μL.
CONCLUSIONS: Low and high blood eosinophil counts in hospitalized patients with AECOPD provide a practical clinical distinction that can potentially be used to inform management strategies. Prospective studies are needed to evaluate if this strategy can guide discriminate use of antibiotics and/or corticosteroids.

Ⅱ．門脈圧亢進症に関する以下の文章を和訳しなさい。

Portal hypertension is defined as the elevation of the hepatic venous pressure gradient (HVPG) to >5 mmHg. Portal hypertension is caused by a combination of two simultaneously occurring hemodynamic processes: (1) increased intrahepatic resistance to the passage of blood flow through the liver due to cirrhosis and regenerative nodules, and (2) increased splanchnic blood flow secondary to vasodilation within the splanchnic vascular bed. Portal hypertension is directly responsible for the two major complications of cirrhosis: variceal hemorrhage and ascites. Variceal hemorrhage is an immediate life-threatening problem with a 20-30% mortality rate associated with each episode of bleeding. The portal venous system normally drains blood from the stomach, intestines, spleen, pancreas, and gallbladder, and the portal vein is formed by the confluence of the superior mesenteric and splenic veins. Deoxygenated blood from the small bowel drains into the superior mesenteric vein along with blood from the head of the pancreas, the ascending colon, and part of the transverse colon. Conversely, the splenic vein drains the spleen and the pancreas and is joined by the inferior mesenteric vein, which brings blood from the transverse and descending colon as well as from the superior two-thirds of the rectum. Thus, the portal vein normally receives blood from almost the entire GI tract.

次の各問いに対する答えを解答用紙に記入しなさい。

1．急性好酸球性肺炎に関する以下の文章を和訳しなさい。

At presentation, acute eosinophilic pneumonia is often mistaken for acute lung injury or acute respiratory distress syndrome (ARDS), until a BAL is performed and reveals >25% eosinophils.  Although the predominant symptoms of acute eosinophilic pneumonia are cough, dyspnea, malaise, myalgias, night sweats, and pleuritic chest pain, physical examination findings include high fevers, basilar rales, and rhonchi on forced expiration.  Acute eosinophilic pneumonia most often affects males between age 20 and 40 with no history of asthma.  Although no clear etiology has been identified, several case reports have linked acute eosinophilic pneumonia to recent initiation of tobacco smoking or exposure to other environmental stimuli including dust from indoor renovations.  In addition to a suggestive history, the key to establishing a diagnosis of acute eosinophilic pneumonia is the presence of >25% eosinophilia on BAL fluid.  While lung biopsies show eosinophilic infiltration with acute and organizing diffuse alveolar damage, it is generally not necessary to proceed to biopsy to establish a diagnosis.  Although patients present with an elevated white blood cell count, in contrast to other pulmonary eosinophilic syndromes, acute eosinophilic pneumonia is often not associated with peripheral eosinophilia upon presentation.  However, between 7 and 30 days of disease onset, peripheral eosinophilia often occurs with mean eosinophil counts of 1700.

2．僧帽弁逆流に関する以下の文章を和訳しなさい。

Atrial fibrillation (AF) is the most common rhythm disorder observed in 2% of the general population and the prevalence is further increasing as the society is aging. It is well known that atrial fibrillation (AF) causes left atrial (LA) and mitral annular dilatation without left ventricular (LV) dysfunction. However, whether AF and succeeding annular dilatation cause significant mitral regurgitation (MR) without LV dysfunction remains controversial. It had been widely recognized that MR can occur without significant degenerative changes of the mitral leaflets in patients with severe left heart dilatation or LV dysfunction caused either by ischemic heart disease or idiopathic myocardial disease. These types of MR were called functional (secondary) MR in contrast to degenerative (primary) MR caused by the organic change of mitral valve itself. Research performed during the early era of 2-dimensional echocardiography (2DE) reported annular dilatation as the primary mechanism related to functional MR caused by LV dilatation/dysfunction. Then, significant evolution in imaging techniques including 3-dimensional echocardiography (3DE) enabled more detailed and comprehensive observation in mitral valve morphology, and later studies using 3DE revealed that the primary mechanism of this MR is attributable to tethering of the mitral valve caused by the dilated LV and displaced papillary muscle rather than mitral annular dilatation.

次の各問いに対する答えを解答用紙に記入しなさい。

1．腸管免疫に関する以下の文章を和訳しなさい。

T cells are found within the gut epithelial layer, scattered throughout the lamina propria and submucosa, and around and within follicles in Peyer's patches and other GALT structures. In humans, most of the intraepithelial T cells are CD8+ cells. In mice, about 50% of intraepithelial lymphocytes express the γδ form of the TCR, similar to intraepidermal lymphocytes in the skin. In humans, only about 10% of intraepithelial lymphocytes are γδ cells, but this proportion is still higher than the percentages of γδ cells among T cells in other tissues. Both the αβ and the γδ TCR-expressing intraepithelial lymphocytes have a limited diversity of antigen receptors, and thus a limited range of specificities compared to most T cells. This restricted repertoire may have evolved to recognize microbes that are commonly encountered at the epithelial surface. Lamina propria T cells are mostly CD4+, and most have the phenotype of activated effector or memory T cells, the latter with an effector memory phenotype. Many of these memory T cells are noncirculating tissue-resident memory cells. Recall that these lamina propria effector and memory T cells are generated from naive precursors in the GALT and mesenteric lymph nodes, enter the circulation, and preferentially home back into the lamina propria. T cells within Peyer's patches and in other follicles adjacent to the intestinal epithelium are mostly CD4+ helper T cells, including follicular helper T cells and regulatory T cells.

2．大動脈弁狭窄症に関する以下の文章を和訳しなさい。

Aortic stenosis (AS) is the most common valvular heart disease (VHD), with a prevalence >4% in octogenarians. The pressure overload associated with AS leads to development of left ventricular (LV) concentric hypertrophy, impairment of LV diastolic and systolic function, and ultimately, heart failure (HF). In the absence of treatment, symptomatic severe AS is associated with poor prognosis. However, aortic valve replacement may change the natural history of AS and restore a patient's life expectancy close to that of the age- and sex-matched general population. Cardiac amyloidosis (CA) is characterized by extracellular deposit of amyloid fibrils within the myocardium and other cardiac structures; this condition afflicts ≤25% of octogenarians. CA shares several common features with AS, but its prognosis generally is worse than severe AS alone. Recent studies suggest that the coexistence of AS and CA is more common than previously anticipated. The combination of AS and CA complicates the diagnosis and therapeutic management of both conditions. Recently, effective pharmacotherapies have been developed to halt and reverse the course of transthyretin (TTR) CA. There is thus an urgent need to standardize and optimize the diagnostic evaluation and therapeutic management of CA in AS, and vice versa.

次の各問いに対する答えを解答用紙に記入しなさい。

1．JAK阻害薬であるBaricitinibに関する以下の文章を和訳しなさい。

In the present pandemic of coronavirus disease-19 (COVID-19), baricitinib has gained considerable interest because of its protective and curative effects on SARS-CoV-2 infection.  It has been shown that baricitinib prevents virus endocytosis and reduces viral assembly by inhibiting adaptor-related protein-2 (AP- 2)–associated protein kinase 1 and cyclin-G-associated kinase enzymes in alveolar type 2 cells.  Because these cells contribute to viral transmission, baricitinib might hinder viral entrance to the underlying tissue.  Baricitinib could also exert beneficial effects in treating acute respiratory distress syndrome in COVID-19 patients by alleviating exaggerated inflammatory responses.  An in vitro study investigating the effect of baricitinib on cytokine release from whole blood cells of COVID-19 patients in response to SARS-CoV-2 antigens demonstrated decreased spike-specific responses consequent to the reduced expression of IFN-γ, IL-17, IL-1β, IL-6, TNF-α, and other inflammatory cytokines.  Although cytokine inhibition is helpful for managing severe cases of COVID-19, the essential role of cytokines, particularly IFNs, in eradicating viral infection should be taken into consideration.  Therefore, JAK inhibitors are supposed to be administered preferentially to critical patients for a limited period and regarding their cytokine profiles.

2．肝腫瘍に関する以下の文章を和訳しなさい。

Hepatic adenomas are clonal benign proliferations resulting from single gene driver mutations.  HCA (hepatocellular adenoma) have a low prevalence of 0.001% of the population and are frequently diagnosed in women aged 35-40 years.  The female:male ratio is 10:1, and the main risk factors are oral contraceptives in females and use of anabolic androgenic steroids in male body builders.  HCA have the potential for hemorrhage and HCC development, particularly when sized >5 cm.  Nowadays, there is a clear understanding of the molecular classification of HCA: (a) HCA with CTNNB1 mutations (10-20%) are at-risk of HCC development and are present in men treated with androgens; (b) inflammatory adenomas (50-60%) are associated with single mutations (Gp130:65%) and are more prevalent in females with obesity or diabetes; and (c) adenomas with inactivated HNF-1A.  Diagnosis is based on MRI imaging, which is able to correlate with molecular subtypes in 80% of cases (Inflammatory and HNF-1A type).  For defining HCA with CTNNB1 mutations, biopsy is required.  Upon diagnosis, discontinuation of oral contraceptives and weight loss is recommended.  Resection is indicated in all cases of size >5 cm or men or CTNNB1 mutation.  For HCA <5 cm, 1-year follow-up is recommended.  In case of active HCA bleeding, embolization followed by resection is the treatment of choice.  The presence of multiple HCA is common, and guidelines endorse treating them based on the size of the main nodule.

次の各問いに対する答えを解答用紙に記入しなさい。

1．NPSLEに関する以下の文章を和訳しなさい。

No clear evidence has yet been found regarding the treatment of neuropsychiatric manifestation of SLE (NPSLE). Various immunosuppressive treatments have been introduced for a variety of NP symptoms in patients with SLE. Cyclophosphamide is the only drug that has been compared with steroid pulse therapy in a randomized controlled trial and has been found more useful than steroid pulse therapy. However, the evidence from this study is considered insufficient due to the characteristics of the patients. For instance, most patients had epilepsy or peripheral neuropathy, and some had optic neuritis. Azathioprine can be used as a maintenance therapy or to reduce the steroid dosage applied. Azathioprine used as a maintenance therapy has been shown to suppress the recurrence of NP manifestations in patients with NPSLE. Mycophenolate mofetil (MMF) is widely used as the first-line option for both the induction and maintenance therapies for lupus nephritis. Several observational studies have suggested the potential benefit of MMF in the non-renal manifestations of SLE. However, it is difficult to make any definite conclusion. The effectiveness of rituximab against refractory NPSLE has previously been reported by Tokunaga et al. In a systematic review, clinical response to rituximab has been detected in 85% of patients with NPSLE. However, two SLE patients under rituximab treatment have died due to progressive leukoencephalopathy, and thus the clinical trial has been aborted.

2．COVID-19に関する以下の文章を和訳しなさい。

The pandemic of novel coronavirus disease (COVID-19) has developed as a tremendous threat to global health. Although most COVID-19 patients present with respiratory symptoms, some present with gastrointestinal (GI) symptoms like diarrhoea, loss of appetite, nausea/vomiting and abdominal pain as the major complaints. These features may be attributable to the following facts: (a) COVID-19 is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and its receptor angiotensin converting enzyme 2 (ACE2) was found to be highly expressed in GI epithelial cells, providing a prerequisite for SARS-CoV-2 infection; (b) SARS-CoV-2 viral RNA has been found in stool specimens of infected patients, and 20% of patients showed prolonged presence of SARS-CoV-2 RNA in faecal samples after the virus converting to negative in the respiratory system. These findings suggest that SARS-CoV-2 may be able to actively infect and replicate in the GI tract. Moreover, GI infection could be the first manifestation antedating respiratory symptoms; patients suffering only digestive symptoms but no respiratory symptoms as clinical manifestation have also been reported. Thus, the implications of digestive symptoms in patients with COVID-19 is of great importance.

次の各問いに対する答えを解答用紙に記入しなさい。

1．結核性腹膜炎に関する以下の文章を和訳しなさい。

Tuberculous peritonitis is an uncommon site of extrapulmonary infection caused by M. tuberculosis. Patients with HIV infection, cirrhosis, diabetes mellitus, and underlying malignancy are at increased risk. Noncirrhotic patients with tuberculous peritonitis usually have ascites with a high protein content, low glucose concentration, and a low serum-to-ascites albumin gradient (<1.1 g/dL). Patients almost always have an elevated ascitic fluid WBC count with a lymphocytic predominance. The algorithm in evaluation of patients with ascitic fluid that has a high lymphocyte count includes cytologic evaluation of the fluid and consideration of laparoscopy. Patients with lymphocytic ascites and fever usually have TB, whereas afebrile patients usually have malignancy-related ascites. Cancer is the cause of lymphocytic ascites about 10 times more frequently than TB. If peritoneal metastases are present, the cytologic findings are positive more than 90% of the time, and the laparoscopy can be avoided. If the cytology is negative, however, laparoscopy is performed and is nearly 100% sensitive in detecting tuberculous peritonitis. However, a number of noninvasive diagnostic tests are available to diagnose extrapulmonary disease. Adenosine deaminase levels are typically elevated in the ascitic fluid in tuberculous ascites, and this finding can help differentiate tuberculous peritonitis from peritoneal carcinomatosis. An enzyme-linked immunospot assay (ELISPOT) and PCR assay (Xpert MTB/RIF) are novel, rapid, noninvasive tests for M. tuberculosis. Tuberculous peritonitis may also appear as a pelvic mass on CT, with high serum levels of CA125, making the diagnosis difficult to distinguish from metastatic ovarian cancer.

2．I期とII期の非小細胞肺癌（NSCLC）の放射線療法に関する以下の文章を和訳しなさい。

There is currently no role for postoperative radiation therapy in patients following resection of stage I or II NSCLC with negative margins. However, patients with stage I and II disease who either refuse or are not suitable candidates for surgery should be considered for radiation therapy with curative intent. Stereotactic body radiation therapy (SBRT) is a technique used to treat patients with isolated pulmonary nodules (≤5 cm) who are not candidates for or refuse surgical resection. Treatment is typically administered in three to five fractions delivered over 1-2 weeks. In uncontrolled studies, disease control rates are >90%, and 5-year survival rates of up to 60% have been reported with SBRT. By comparison, survival rates typically range from 13 to 39% in patients with stage I or II NSCLC treated with standard external-beam radiotherapy. Cryoablation is another technique occasionally used to treat small, isolated tumors (i.e., ≤3 cm). However, very little data exist on long-term outcomes with this technique.

次の各問いに対する答えを解答用紙に記入しなさい。

Ⅰ．家族性地中海熱に関する以下の文章を和訳しなさい。

Familial Mediterranean fever (FMF), an autosomal recessive disease, is characterized by recurrent self-limited attacks of fever, joint pain, and abdominal pain, most commonly in people of Mediterranean origin. The gene responsible for FMF, MEFV on chromosome 16, encodes the protein pyrin. MEFV gene analysis assists in diagnosis. Patients develop what appears to be an acute abdomen due to peritonitis. Their severe abdominal pain is reduced by lying motionless with hips flexed. The abdomen is rigid with rebound tenderness, reduced bowel sounds, and abdominal distension. There may be multiple air-fluid levels, a leukocytosis with a left shift, an increased ESR, and elevated acute-phase reactants. The attack begins to subside after 24 hours. Peritonitis results in protein- rich sterile exudates with fibrin and neutrophils that, when organized, may lead to adhesions and small bowel obstruction, sometimes with strangulation and necrosis. Patients are asymptomatic between episodes, although acute-phase reactants may be elevated, indicating subclinical inflammation. Serum amyloid concentration increases dramatically during febrile attacks. AA amyloidosis may develop independent of the frequency, duration, and intensity of flare-ups. Kidney impairment is the most clinically significant result, but amyloid can deposit in the GI tract and cause symptoms after many years. FMF is associated with other diseases such as IBD, some vasculitides, and irritable bowel syndrome. GI mucosal involvement may suggest IBD but mucosal healing can be achieved with colchicine alone.

Ⅱ．心不全と間質線維化に関する以下の文章を和訳しなさい。

Heart failure is accompanied by the progressive accumulation of interstitial collagen fibers, which decrease the myocardial contractility and compliance, and therefore cause ventricular systolic and/or diastolic dysfunction. The exact mechanism of these fibrotic changes is still unclear, but there are two main theories. First, it is thought that a reactive collagen fiber accumulation occurs in the interstitium and perivascular regions and leads to fibrotic changes. On the other hand, an adaptive, reparative fibrosis due to myocyte loss is suspected. Not only the amount of the cardiac collagen changes in heart failure, but also the quality with a shift from insoluble to soluble collagen, leading to reduced myocardial cross-linking and therefore an impaired ventricular contraction. The formed fibrotic tissue is a dynamic structure, metabolically active, contractile, and is able to adapt to changing circumstances. Due to interstitial fibrosis, the capillary density also reduces, which results in an impaired oxygen supply of the tissues and therefore hypoxia-induced structural changes and apoptosis/necrosis of the cells.

次の各問いに対する答えを解答用紙に記入しなさい。

Ⅰ．血管浮腫に関する以下の文章を和訳しなさい。

Recurrent angioedema of the skin is a commonly diagnosed clinical symptom that can be seen in various clinical entities. Some types of angioedema of the skin are associated with episodes of upper-airway obstruction that might be life-threatening. Asphyxiation by laryngeal oedema is well known in hereditary angioedema (HAE) due to C1-inhibitor (deficiency) and in recurrent angioedema induced by angiotensin-converting-enzyme (ACE) inhibitors. Therefore, the exact type of angioedema must be identified in each patient. In many patients, angioedema is associated with urticaria. If relapsing urticaria occurs simultaneously or otherwise with angioedema, the two disorders are assumed to be symptoms of the same disease. Recurrent angioedema without urticaria can result from inherited or acquired C1-inhibitor deficiency, or be induced by ACE inhibitors. HAE due to C1-inhibitor deficiency is not associated with urticaria, whereas ACE inhibitors may cause recurrent angioedema alone, or in association with urticaria. In recurrent angioedema C1-inhibitor deficiency, antihistamines and corticosteroids are not effective. Other types of angioedema without urticaria are rare and include local angioedema secondary to physical stress, such as vibratory angioedema. Some patients with recurrent angioedema have clinical symptoms that cannot be ascribed to one of these disorders. This type of angioedema is referred to as idiopathic angioedema.

Ⅱ．Covid-19入院患者におけるデキサメタゾン使用に関する以下の文章を和訳しなさい。

In this controlled, open-label trial comparing a range of possible treatments in patients who were hospitalized with Covid-19, we randomly assigned patients to receive oral or intravenous dexamethasone (at a dose of 6 mg once daily) for up to 10 days or to receive usual care alone. The primary outcome was 28-day mortality. Here, we report the preliminary results of this comparison. A total of 2104 patients were assigned to receive dexamethasone and 4321 to receive usual care. Overall, 483 patients (22.9%) in the dexamethasone group and 1110 patients (25.7%) in the usual care group died within 28 days after randomization (age-adjusted rate ratio, 0.83; 95% confidence interval [CI], 0.75 to 0.93; P<0.01). The proportional and absolute between-group differences in mortality varied considerably according to the level of respiratory support that the patients were receiving at the time of randomization. In the dexamethasone group, the incidence of death was lower than that in the usual care group among patients receiving invasive mechanical ventilation (29.3% vs. 41.4%; rate ratio, 0.64; 95% CI, 0.51 to 0.81) and among those receiving oxygen without invasive mechanical ventilation (23.3% vs. 26.2%; rate ratio, 0.82; 95% CI, 0.72 to 0.94) but not among those who were receiving no respiratory support at randomization (17.8% vs. 14.0%; rate ratio 1.19; 95% CI, 0.91 to 1.55). In patients hospitalized with Covid-19, the use of dexamethasone resulted in lower 28-day mortality among those who were receiving either invasive mechanical ventilation or oxygen alone at randomization but not among those receiving no respiratory support.

次の各問いに対する答えを解答用紙に記入しなさい。

1．結核性腹膜炎に関する以下の文章を和訳しなさい。

Tuberculous peritonitis is an uncommon site of extrapulmonary infection caused by M. tuberculosis. Patients with HIV infection, cirrhosis, diabetes mellitus, and underlying malignancy are at increased risk. Noncirrhotic patients with tuberculous peritonitis usually have ascites with a high protein content, low glucose concentration, and a low serum-to-ascites albumin gradient (<1.1 g/dL). Patients almost always have an elevated ascitic fluid WBC count with a lymphocytic predominance. The algorithm in evaluation of patients with ascitic fluid that has a high lymphocyte count includes cytologic evaluation of the fluid and consideration of laparoscopy. Patients with lymphocytic ascites and fever usually have TB, whereas afebrile patients usually have malignancy-related ascites. Cancer is the cause of lymphocytic ascites about 10 times more frequently than TB. If peritoneal metastases are present, the cytologic findings are positive more than 90% of the time, and the laparoscopy can be avoided. If the cytology is negative, however, laparoscopy is performed and is nearly 100% sensitive in detecting tuberculous peritonitis. However, a number of noninvasive diagnostic tests are available to diagnose extrapulmonary disease. Adenosine deaminase levels are typically elevated in the ascitic fluid in tuberculous ascites, and this finding can help differentiate tuberculous peritonitis from peritoneal carcinomatosis. An enzyme-linked immunospot assay (ELISPOT) and PCR assay (Xpert MTB/RIF) are novel, rapid, noninvasive tests for M. tuberculosis. Tuberculous peritonitis may also appear as a pelvic mass on CT, with high serum levels of CA125, making the diagnosis difficult to distinguish from metastatic ovarian cancer.

2．I期とII期の非小細胞肺癌（NSCLC）の放射線療法に関する以下の文章を和訳しな さい。

There is currently no role for postoperative radiation therapy in patients following resection of stage I or II NSCLC with negative margins. However, patients with stage I and II disease who either refuse or are not suitable candidates for surgery should be considered for radiation therapy with curative intent. Stereotactic body radiation therapy (SBRT) is a technique used to treat patients with isolated pulmonary nodules (≤5 cm) who are not candidates for or refuse surgical resection. Treatment is typically administered in three to five fractions delivered over 1-2 weeks. In uncontrolled studies, disease control rates are >90%, and 5-year survival rates of up to 60% have been reported with SBRT. By comparison, survival rates typically range from 13 to 39% in patients with stage I or II NSCLC treated with standard external-beam radiotherapy. Cryoablation is another technique occasionally used to treat small, isolated tumors (i.e., ≤3 cm). However, very little data exist on long-term outcomes with this technique.

次の各問いに対する答えを解答用紙に記入しなさい。

Ⅰ．Measlesに関する以下の文章を和訳しなさい。（下線部の訳は下記を参照すること）

Measles is an acute viral illness that starts with a prodromal phase, lasting 2 to 4 days, of fever and at least one of the “three Cs” (cough, coryza, and conjunctivitis), similar to any upper respiratory tract infection. The characteristic measles rash — an erythematous maculopapular exanthema　— appears 2 to 4 days after the onset of fever, first on the face and head and then on the trunk and extremities; it may be confluent on the face and upper body. During the ensuing 3 to 5 days, the rash in different parts of the body fades in the order in which it appeared, and full recovery occurs within 7 days after rash onset in uncomplicated cases. Koplik spots, small bluish white plaques on the buccal mucosa, are present in up to 70% of cases and are considered pathognomonic of measles; they may appear 1 to 2 days before the onset of rash and may be present for an additional 1 to 2 days after rash onset. Complications associated with measles infection in industrialized countries include otitis media (7 to 9% of patients), pneumonia (1 to 6%), diarrhea (8%), postinfectious encephalitis (approximately 1 per 1000), subacute sclerosing panencephalitis (a progressive degenerative disease with onset usually 5 to 10 years after acute measles; approximately 1 per 10,000), and death (approximately 1 per 1000). an erythematous maculopapular exanthema：紅斑性丘疹 pathognomonic :（疾患に）特徴的な

Ⅱ．僧帽弁逸脱に関する以下の文章を和訳しなさい。

Mitral Valve Prolapse (MVP) is a common disorder afflicting 2-3% of the general population. It is characterized by typical fibromyxomatous changes in the mitral leaflet tissue with superior displacement of one or both leaflets into the left atrium. MVP can be associated with significant mitral regurgitation (MR), bacterial endocarditis, congestive heart failure, and even sudden death. MVP is a clinical entity that is not fully understood, despite being known for more than a century. A ‘mid-systolic click’ was first described in 1887 by Cuffer and Barbillon. In 1963 Barlow demonstrated the presence of MR by angiography in patients with the ‘click-murmur’ syndrome. Criley subsequently coined the term mitral valve prolapse. MVP may be familial or sporadic. Despite being the most common cause of isolated MR requiring surgical repair, little is known about the genetic mechanisms underlying the pathogenesis and progression of MVP. Studies on the heritable features of MVP have been limited by the analysis of relatively small pedigrees and by self-referral and selection biases, including a preponderance of data from hospital-based cohorts. Nonetheless, a majority of data favors an autosomal dominant pattern of inheritance in a large proportion of individuals with MVP. Despite the variability in the clinical features, familial MVP might be considered a prevalent Mendelian cardiac abnormality in humans. While filamin A has been identified as causing an X-linked form of MVP, the causative genes for the more common form of autosomal dominant MVP have yet to be defined.

次の各問いに対する答えを解答用紙に記入しなさい。

Ⅰ．急性大動脈解離に関する以下の文章を和訳しなさい。

Acute aortic dissection is a rare but life-threatening condition with a lethality rate of 1 to 2% per hour after onset of symptoms in untreated patients. Therefore, its prompt and proper diagnosis is vital to increase a patient’s chance of survival and to prevent grievous complications. Typical symptoms of acute aortic dissection include severe chest pain, hypotension or syncope and, hence, mimic acute myocardial infarction or pulmonary embolism. Advanced age, male gender, long-term history of arterial hypertension and the presence of aortic aneurysm confer the greatest population attributable risk. However, patients with genetic connective tissue disorders such as Marfan, Loeys Dietz or Ehlers Danlos syndrome, and patients with bicuspid aortic valves are at the increased risk of aortic dissection at a much younger age. Imaging provides a robust foundation for diagnosing acute aortic dissection, as well as for monitoring of patients at increased risk of aortic disease. As yet, easily accessible blood tests play only a small role but have the potential to make diagnosis and monitoring of patients simpler and more cost-effective.

Ⅱ．レジオネラ肺炎に関する以下の文章を和訳しなさい。

Legionnaires’ disease is often included in the differential diagnosis of “atypical pneumonia,” along with pneumonia due to C. pneumoniae, Chlamydia psittaci, Mycoplasma pneumoniae, Coxiella burnetii, and some viruses. The clinical similarities among “atypical” pneumonias include a nonproductive cough with a low frequency of grossly purulent sputum. The clinical manifestations of Legionnaires’ disease are usually more severe than those of most “atypical” pneumonias. The course and prognosis of Legionella pneumonia more closely resemble those of bacteremic pneumococcal pneumonia than those of pneumonia due to other “atypical” pathogens. Patients with community-acquired Legionnaires’ disease are significantly more likely than patients with pneumonia of other etiologies to be admitted to an intensive care unit (ICU) on presentation. The mild cough of Legionnaires’ disease is only slightly productive. Sometimes the sputum is streaked with blood. Chest pain – either pleuritic or nonpleuritic – can be a prominent feature and, when coupled with hemoptysis, can lead to an incorrect diagnosis of pulmonary embolism. Shortness of breath is reported by one-third to one-half of patients. Gastrointestinal difficulties are often pronounced; abdominal pain, nausea, and vomiting affect 10-20% of patients. Diarrhea (watery rather than bloody) is reported in 25-50% of cases. The most common neurologic abnormalities are confusion or changes in mental status.

次の各問いに対する答えを解答用紙に記入しなさい。

Ⅰ．腹部身体所見に関する以下の文章を和訳しなさい。

Physical examination should include an assessment for signs of systemic disease. The presence of lymphadenopathy, especially supraclavicular lymphadenopathy (Virchow’s node), suggests metastatic abdominal malignancy. The abdominal examination should begin with inspection for the presence of uneven distention or an obvious mass. Auscultation should follow. The absence of bowel sounds or the presence of high-pitched localized bowel sounds points toward an ileus or intestinal obstruction. An umbilical venous hum may suggest the presence of portal hypertension, and a harsh bruit over the liver is heard rarely in patients with hepatocellular carcinoma or alcoholic hepatitis. Abdominal swelling caused by intestinal gas can be differentiated from swelling caused by fluid or a solid mass by percussion; an abdomen filled with gas is tympanic, whereas an abdomen containing a mass or fluid is dull to percussion. The absence of abdominal dullness, however, does not exclude ascites, because a minimum of 1500 mL of ascitic fluid is required for detection on physical examination. Finally, the abdomen should be palpated to assess for tenderness, a mass, enlargement of the spleen or liver, or presence of a nodular liver suggesting cirrhosis or tumor. Light palpation of the liver may detect pulsations suggesting retrograde vascular flow from the heart in patients with right-sided heart failure, particularly tricuspid regurgitation.

Ⅱ．結核（TB）の薬物療法に関する以下の文章を和訳しなさい。

The two aims of TB treatment are (1) to prevent morbidity and death by curing TB while preventing the emergence of drug resistance and (2) to interrupt transmission by rendering patients noninfectious. Chemotherapy for TB became possible with the discovery of streptomycin in 1943. Randomized clinical trials clearly indicated that the administration of streptomycin to patients with chronic TB reduced mortality rates and led to cure in the majority of cases. However, monotherapy with streptomycin eventually was associated with the development of resistance to this drug and the resulting failure of treatment. With the introduction into clinical practice of paraaminosalicylic acid (PAS) and isoniazid, it became axiomatic in the early 1950s that cure of TB required the concomitant administration of at least two agents to which the organism was susceptible. Furthermore, early clinical trials demonstrated that a long period of treatment―i.e., 12-24 months―was required to prevent recurrence. The introduction of rifampin (rifampicin) in the early 1970s heralded the era of effective short-course chemotherapy, with a treatment duration of <12 months. The discovery that pyrazinamide, which was first used in the 1950s, augmented the potency of isoniazid/rifampin regimens led to the use of a 6-month course of this triple-drug regimen as standard therapy.

次の各問いに対する答えを解答用紙に記入しなさい。

Ⅰ．管腔臓器の閉塞に関する以下の文章を和訳しなさい。

Intraluminal obstruction classically elicits intermittent or colicky abdominal pain that is not as well localized as the pain of parietal peritoneal irritation. However, the absence of cramping discomfort should not be misleading because distention of a hollow viscus may also produce steady pain with only rare paroxysms. Small-bowel obstruction often presents as poorly localized, intermittent periumbilical or supraumbilical pain. As the intestine progressively dilates and loses muscular tone, the colicky nature of the pain may diminish. With superimposed strangulating obstruction, pain may spread to the lower lumbar region if there is traction on the root of the mesentery. The colicky pain of colonic obstruction is of lesser intensity, is commonly located in the infraumbilical area, and may often radiate to the lumbar region. Sudden distention of the biliary tree produces a steady rather than colicky type of pain; hence, the term biliary colic is misleading. Acute distention of the gallbladder usually causes pain in the right upper quadrant with radiation to the right posterior region of the thorax or to the tip of the right scapula, but it is also not uncommonly found near the midline. Distention of the common bile duct often causes epigastric pain that may radiate to the upper lumbar region. Considerable variation is common, however, so that differentiation between these may be impossible. The typical subscapular pain or lumbar radiation is frequently absent.

Ⅱ．慢性空洞性肺アスペルギルス症に関する以下の文章を和訳しなさい。

The hallmark of chronic cavitary pulmonary aspergillosis is one or more pulmonary cavities expanding over a period of months or years in association with pulmonary symptoms and systemic manifestations such as fatigue and weight loss. (Pulmonary aspergillosis developing over <3 months is better classified as subacute invasive aspergillosis.) Often mistaken initially for tuberculosis, almost all cases occur in patients with prior pulmonary disease (e.g., tuberculosis, atypical mycobacterial infection, sarcoidosis, rheumatoid lung disease, pneumothorax, bullae) or lung surgery. The onset is insidious, and systemic features may be more prominent than pulmonary symptoms. Cavities may have a fluid level or a well-formed fungal ball, but pericavitary infiltrates and multiple cavities―with or without pleural thickening―are typical. An irregular internal cavity surface and thickened cavity walls are indicative of disease activity. IgG antibodies to Aspergillus are almost always detectable in blood, and levels fall slowly with successful therapy. Some patients have concurrent infections―even without a fungal ball―with atypical mycobacteria and/or other bacterial pathogens. One or more Aspergillus nodules that resemble early lung carcinoma and may cavitate have been recognized. If untreated, chronic pulmonary aspergillosis typically progresses (sometimes relatively rapidly) to unilateral or upper lobe fibrosis.

次の各問いに対する答えを解答用紙に記入しなさい。

Ⅰ．Fever of unknown origin (FUO)に関する以下の文章を和訳しなさい。

The differential diagnosis of fever of unknown origin (FUO) can be subdivided in four categories: infections, malignancies, noninfectious inflammatory diseases (NIID), and miscellaneous causes. In Western countries, infections account for one-fifth of FUO cases, with next in frequency NIID and malignancies. In non-Western countries, infections (mostly tuberculosis) are a much more common cause of FUO (43% vs 17%) with similar cases due to NIID and malignancies. In most cases of FUO, there is an uncommon presentation of a common disease. Important for diagnosing FUO is a search for potentially diagnostic clues (PDCs) in a complete and repeated history-taking, physical examination, and the essential investigations. PDCs are defined as all localizing signs, symptoms, and abnormalities potentially indicating a certain diagnosis. Based on these PDCs, a limited list of probable diagnosis can be made. Further diagnostic procedures should be limited to specific investigations to confirm or exclude these possible diseases, because most investigations are helpful only when performed in patients with PDCs for the diagnosis searched for. When PDCs are absent, FDG-PET/CT should be performed to guide additional diagnostic tests. In case of negative FDG-PET/CT and persisting FUO, it is probably more rewarding to wait for new PDCs to appear than immediately perform more screening investigations.

Ⅱ．壁側腹膜の炎症に関する以下の文章を和訳しなさい。

The pain of parietal peritoneal inflammation is steady and aching in character and is located directly over the inflamed area, its exact reference being possible because it is transmitted by somatic nerves supplying the parietal peritoneum. The intensity of the pain is dependent on the type and amount of material to which the peritoneal surfaces are exposed in a given time period. For example, the sudden release into the peritoneal cavity of a small quantity of sterile1) acid gastric juice causes much more pain than the same amount of grossly contaminated neutral feces. Enzymatically active pancreatic juice incites more pain and inflammation than does the same amount of sterile bile containing no potent enzymes. Blood is normally only a mild irritant and the response to urine can be bland2), so exposure of blood and urine to the peritoneal cavity may go unnoticed unless it is sudden and massive. Bacterial contamination, such as may occur with pelvic inflammatory disease or perforated distal intestine, causes low-intensity pain until multiplication causes a significant amount of inflammatory mediators to be released. Patients with perforated upper gastrointestinal ulcers may present entirely differently depending on how quickly gastric juices enter the peritoneal cavity. Thus, the rate at which any inflammatory material irritates the peritoneum is important. 1)無菌の 2)刺激の少ない

次の各問いに対する答えを解答用紙に記入しなさい。

Ⅰ．心臓突然死に関する以下の文章を和訳しなさい。

It is indisputable that sudden cardiac death (SCD) has been and remains a major population burden, even though there have been some notable advances over the years. Examples of the latter include a rapid 50% reduction in mortality from acute myocardial infarction after the development of coronary care units with antiarrhythmic therapy and bedside defibrillators, improvements in resuscitation sciences, and the development and use of implantable cardioverter-defibrillators in a subgroup of appropriately identified high-risk patients. Despite these advances, the opportunities offered by better capabilities for prediction and prevention of cardiac arrest remain an important challenge because ≈90% of victims of sudden cardiac arrest (SCA) occurring out of hospital do not survive, premature SCD and disabilities after SCA survival are a large burden on society because of loss of productive years of life, and healthcare costs attributed to SCA are large and growing. We, as scientific, clinical, and epidemiological communities, have not been successful in addressing many aspects of this challenge. Even elements that intuitively seem simple, such as generating reliable numbers for both events and causes, have been difficult, although they are a key first step for moving from population dynamics to improved individual risk prediction.

Ⅱ．Cough-variant asthmaに関する以下の文章を和訳しなさい。

The typical symptoms of asthma are intermittent episodes of wheezing, chest tightness, breathlessness, and cough. However, a subset of asthmatics will have cough-variant asthma, which manifests as a chronic cough as the only symptom with an otherwise normal physical examination. In studies of patients with chronic cough and a normal chest radiograph, asthma accounted for approximately one-third of all causes. Cough-variant asthma is more common in studies done in China, where it is the most common cause of chronic cough. In patients suspected of having cough-variant asthma, pulmonary function test (PFT) is the initial test and should include forced expiratory volume in 1 second (FEV 1), forced vital capacity (FVC), and FEV 1 -to-FVC ratio. The presence of an airway obstruction that improves after the administration of a bronchodilator agent is highly suggestive of asthma. The authors also recommend simultaneously assessing lung volume and diffuse capacity, in case the airway obstruction is irreversible, which would point toward a diagnosis of COPD. Failure to demonstrate a reversible airway obstruction does not exclude the diagnosis of asthma, and bronchoprovocation testing1), such as the methacholine2) inhalation challenge, can be considered to confirm the diagnosis. The negative predictive value of a methacholine challenge test is reported to be close to 100, so a negative result essentially rules out asthma. According to the American College of Chest Physicians (ACCP), if methacholine challenge is not available or cannot be performed, empiric antiasthma treatment is indicated. 1)気管支吸入誘発試験 2)メタコリン