Tolvaptan reduces the required amount of albumin infusion in patients with decompensated cirrhosis with uncontrolled ascites : a multicenter retrospective propensity score-matched cohort study.

Background: The aim of this retrospective study was to determine whether tolvaptan treatment reduces the amount of albumin administered, volume of ascites removed, and frequency of paracentesis procedures in patients with decompensated cirrhosis with uncontrolled ascites with conventional diuretics. Patients and methods: The control (C) group included patients treated with conventional diuretics. The tolvaptan (T) group included patients treated with both tolvaptan and conventional diuretics. Both groups were matched according to baseline parameters. The amount of albumin administered, volume of ascites removed, and frequency of paracentesis within 30 days of onset of uncontrolled ascites were compared between the two groups. Results: After matching, 74 patients (C=37, T=37) were included. Baseline parameters (C vs. T group) were as follows: age, 69.5 ± 9.3 vs. 70.4 ± 11.0 years (p = 0.702) ; males, 24 (64.9%) vs. 25 (67.6%) (p = 0.999) ; patients with hepatocellular carcinoma, 17 (45.9%) vs. 18 (48.6%) (p = 0.999) ; serum albumin levels at treatment initiation, 2.76 ± 0.48 vs. 2.73 ± 0.49 g/dL (p = 0.773), and serum creatinine levels at treatment initiation, 1.18 ± 1.23 vs. 1.09 ± 0.48 g/dL (p = 0.679). In the C vs. T groups, respectively, mean amount of albumin administered was 51.0 ± 31.4 vs. 33.4 ± 29.8 g/month (p = 0.016) ; mean volume of ascites removed was 2,905 ± 4,921 vs. 1,824 ± 3,185 mL/month (p = 0.266) ; and mean frequency of paracentesis was 0.92 ± 1.46 vs. 0.89 ± 1.45 procedures (p = 0.937). Conclusions: Tolvaptan reduced the use of albumin infusion in patients with decompensated cirrhosis and was effective and acceptable for uncontrolled ascites.

A change in the timing for starting systemic therapies for hepatocellular carcinoma: the comparison of sorafenib and lenvatinib as the first-line treatment.

Aim: The aim of this retrospective multicenter study was to evaluate the differences in the timing for starting systemic therapies as the first-line treatment for hepatocellular carcinoma (HCC). Methods: A total of 375 patients with HCC treated with sorafenib from May 2009 to March 2018 and 56 patients treated with lenvatinib from March 2018 to November 2018 at our affiliated hospitals were included in this study. Results: The median ages of the sorafenib and lenvatinib groups were 71.0 (interquartile range [IQR]: 64.0-77.0) and 73.5 (IQR: 68.0 -80.0) years old, and 300 (80.0%) and 42 (75.0%) patients were men, respectively. The Barcelona Clinic Liver Cancer stage was early, intermediate and advanced in 39 patients (10.4%), 133 patients (35.5%) and 203 patients (54.1%) in the sorafenib group and 1 patient (1.8%), 17 patients (30.4%) and 38 patients (67.9%) in the lenvatinib group, respectively. In the analysis of intermediate HCC, patients who satisfied the criteria of TACE failure/refractoriness (P=0.017), those with ALBI grade 1 (P=0.040), and those with a serum AFP level < 200 ng/ml (P=0.027) were found more frequently in the lenvatinib group than in the sorafenib group, with statistical significance. The objective response rate (ORR) of lenvatinib was 34.8% in the overall patients and 46.7% in the intermediate-stage HCC patients, which was significantly higher than sorafenib (P=0.001, P=0.017). Conclusions: The emergence of lenvatinib has encouraged physicians to start systemic chemotherapy earlier in intermediatestage HCC patients.

Faecal lactoferrin is a useful biomarker for mucosal healing in patients with ulcerative colitis during granulocyte and monocyte adsorptive apheresis therapy.

AIM: The study investigated the value of faecal lactoferrin as a follow-up biomarker for mucosal healing of ulcerative colitis during granulocyte and monocyte adsorptive apheresis (GMA) therapy. METHOD: Patients with ulcerative colitis exhibiting a moderate or severe disease activity with a partial Mayo Score (pMS) of over 4 were enrolled in this study. The patients received 10 courses of GMA therapy. The pMS value and faecal lactoferrin level were monitored and compared with the findings of endoscopy until 12 months after the last dose of GMA therapy. RESULTS: Twenty patients (male:female 11:9) were enrolled in this study. Twelve had total colitis, while six had left-sided involvement and two had distal proctitis. Thirteen (65.0%) responded to GMA therapy. The faecal lactoferrin levels were significantly decreased in patients who responded to GMA therapy (P < 0.05), whereas the levels did not change in non-responders. Moreover, the faecal lactoferrin levels correlated with the endoscopic findings (r = 0.792, P < 0.01) and pMS scores (r = 0.529, P < 0.01). The correlation coefficients between the faecal lactoferrin levels and mucosal findings were higher than those observed between the pMS score and mucosal findings. CONCLUSION: The faecal lactoferrin level is a useful biomarker of the mucosal findings in ulcerative colitis. Although endoscopy is the gold standard, the faecal lactoferrin level can be used as a biomarker during GMA therapy in patients with ulcerative colitis.

Case of progressive facial hemiatrophy with cervical sympathetic hyperactivity as underlying aetiology.

OBJECTIVE: We report a case of progressive facial hemiatrophy with cervical sympathetic hyperactivity as a possible underlying aetiology, based on clinical findings, three-dimensional computed tomography and thermographic imaging. METHODS: We present a case report in which we describe the investigation and clinical course of progressive facial hemiatrophy, and we also review the world literature on this condition. RESULTS: To our knowledge, this is the first report in the world literature of progressive facial hemiatrophy with cervical sympathetic hyperactivity indicated as a possible underlying aetiology, based on clinical findings, three-dimensional computed tomography and thermographic imaging. CONCLUSION: This syndrome may lead to atrophy of the subcutaneous adipose tissue with hyperfunction of the vegetative system. Although this is a rare syndrome, otolaryngologists should be aware of its symptoms, aetiology and treatment.

[Interstitial pneumonia, pulmonary thrombotic microangiopathy, and hyperimmunoglobulinemia associated with Basedow's disease].

A 44-year-old man with a history of Basedow's disease complained of dry cough and lymphadenopathy. Polyclonal hypergammaglobulinemia (IgG level: 5,839 mg/dl) was present, and the patient's serum was positive for lupus anticoagulant. Chest radiography disclosed irregular thickening of bronchovascular bundles, centrilobular granular and branching opacities, and small cystic changes in both lung fields. Examination of a thoracoscopic biopsy specimen revealed fibrous thickening of the pleura, interlobular septum, and peribronchiolar/perivascular connective tissue, with mild round-cell infiltration. Lymphoid follicle formation and pulmonary thrombotic microangiopathy were also observed. Corticosteroid therapy was ineffective for hypergammaglobulinemia and diffuse opacities disclosed by chest computed tomographic scans. This case differed from multicentric Castleman's disease with respect to the pathological findings of a lymph nodes biopsy, and also was not consistent with any known collagen vascular disease, (e.g., Sjögren's syndrome). We suspect this case may be representative of a new form of collagen vascular disease.

[A welder with chemical pneumonitis caused by inhalation of zinc fume].

A 61-year-old man with a 32-year occupational history of welding developed malaise, cough, and dyspnea after inhalation of smoke while welding galvanized steel. On admission, peripheral leukocytosis, hypoxemia, and diffuse granular and linear opacities on a chest X-ray were present. The bronchioli were exaggerated in a chest high-resolution CT. Bronchoalveolar lavage revealed mild lymphocytosis and transbronchial lung biopsy showed siderosis and exudation of fibrin and neutrophils into alveolar spaces. The clinical and radiographic findings later improved except for an obstructive disorder on pulmonary function test. The respiratory health hazards associated with welding vary according to the materials and the concentration of inhaled substances. Acute chemical pneumonitis caused by inhalation of zinc fumes (zinc oxide) was accompanied by chronic siderosis in this case. It is well known that metal fume fever commonly occurs when inhaling zinc oxide fumes. However acute chemical pneumonitis after exposure to zinc oxide during welding has been only rarely reported.

Systemic sarcoidosis with significant granulomatous swelling of the pharyngeal tonsil.

A pharyngeal tonsil biopsy specimen from a 27-year-old male revealed epithelioid cell granulomas with noncaseating necrosis. Systemic enlargement of the lymph nodes was present. Plain chest radiographic and computed tomography (CT) images showed ground-glass attenuation in the lungs and bilateral hilar lymphadenopathy. Biopsy of inguinal region nodes confirmed the diagnosis of systemic sarcoidosis. Detailed examination of the nasopharynx should be performed in any case presenting with systemic sarcoidosis because the specimen is readily removable and the pathologic findings of the local lesion may support the diagnosis.

[Microscopic polyangiitis and pulmonary fibrosis in a patient who died of Candida pneumonia and intra-alveolar hemorrhage].

A 74-year-old man was admitted to our hospital because of edema of the lower legs, fever, and increasing fatigue. Laboratory evaluation revealed proteinuria, microhematuria, leukocytosis, thrombocytosis, anemia, a high level of C-reactive protein. A test for myeloperoxidase-antineutrophil cytoplasmic antibodies was highly positive. Microscopic polyarteritis nodosa was diagnosed and therapy with prednisolone was begun. Examination of a renal biopsy sample showed necrotizing crescentic glomerulonephritis. A chest roentgenogram and CT scan disclosed bilateral basilar interstitial changes. Six months later, the patient was admitted again because of disturbance of consciousness, malnutrition, and hyponatremia. After admission, alveolar infiltrates developed in the right lung and the patient died on the 5th hospital day as a result of respiratory failure. An autopsy revealed Candida pneumonia of the right lung and massive intra-alveolar hemorrhage, which was believed to have caused the respiratory failure. Other findings were usual interstitial pneumonia, cellular small-vessel angiitis in the lungs, and healed angiitis in the kidneys and liver. In this case of microscopic polyangiitis and chronic interstitial pneumonia, steroid therapy was effective against the angiitis, but the patient died of an opportunistic infection and alveolar hemorrhage.

[Clinical course of HIV-infected tuberculosis patients who admitted to the tuberculosis isolation ward: current problems of medical care].

To clarify the problems of medical care of HIV-infected tuberculosis patients, we investigated clinical course of six cases admitted to our tuberculosis isolation ward. All cases were sputum smear positive for tubercle bacilli at the time of diagnosis of tuberculosis. HIV-positive was confirmed at the same time or soon after the diagnosis of tuberculosis in four cases. CD4+ cell count was on the average 21/mm3 on admission, and all cases were defined as acquired immunodeficiency syndrome (AIDS) by the criteria of AIDS surveillance committee in Japan. Two patients presented with miliary tuberculosis and five documented evidence for intrathoracic and/or cervical lymph node involvement. All cases but one responded well to antituberculosis drugs, and sputum smears and cultures became negative soon after the initiation of therapy. However, the patients were still needed to be hospitalized for the treatment and control of complications other than tuberculosis after sputum negative conversion, and they stayed in the isolation rooms of our tuberculosis ward for 110 +/- 49 days. During the treatment for tuberculosis, each patient developed 3 to 8 complications of HIV infection such as pneumocystis carinii pneumonia (PCP) (four cases), bacterial infection (four cases), neuropathy (four cases), and HIV encephalopathy (three cases). The last two complication worsened active daily life. White blood cell count was more likely to fall when sulfamethoxazole/trimethoprim mixture for the prevention of PCP and antituberculosis drugs were administered together. In three cases, ST mixture could not be continued, then two patients developed PCP after changing to an alternative pentamidine inhalation. Although three patients discharged from our tuberculosis ward, four died of AIDS related complications other than tuberculosis, one died of tuberculosis (multidrug-resistant M. tuberculosis strain was not documented initially but was detected five months later), one died of tuberculosis meningitis after the discharge, and one was lost because he returned to his own country. The survival time between the start of treatment and death ranged from 90 to 244 days in five cases. Integrated medical care system both for HIV and tuberculosis is warranted for the management of HIV-infected tuberculosis patients since they suffer many complication in addition to tuberculosis. A guideline of methods and duration of isolation for tuberculosis is needed for the most effective care of HIV-infected tuberculosis patients in Japan.

Stroboscopic observation of the larynx after radiation in patients with T1 glottic carcinoma.

We studied laryngeal video stroboscopy (LVS) system for evaluation of patients with glottic carcinoma (T1N0M0) before and after radiotherapy. There were 10 patients with T1 glottic squamous cell carcinoma (9 men and 1 woman) who received radiotherapy at the Hitachi General Hospital. We performed LVS before and after radiotherapy. The presence or absence of mucosal waves (MW) was particularly noted. No MW were present before radiotherapy but at 1-6 months after, MW gradually appeared. One year after radiotherapy all patients showed MW on LVS. In patients with glottic carcinoma MW recovered after radiation therapy. LVS may be useful for the clinical follow-up of post-radiation patients for early detection of recurrence of glottic carcinoma.

[Chronic pulmonary mucormycosis that developed in preexisting cavities caused by tuberculosis in a patient with diabetes mellitus and liver cirrhosis].

We describe a case of chronic pulmonary mucormycosis. The patient was a 44-year-old man with diabetes mellitus and alcoholic liver cirrhosis. He had been treated for pulmonary tuberculosis three years earlier and thin-walled cavities remained in the left upper lobe. He presented with coughing, sputum, and fever, and a chest radiograph and CT scan showed increased consolidation around the preexisting cavities in the left lung, along with a small round opacity in the right upper lobe. Transbronchial lung biopsy of the left upper lobe revealed pulmonary mucormycosis with necrosis. Treatment with amphotericin B for two months was not completely successful, particularly with regard to the lesion on the left, so surgery was done. A left upper lobectomy and a left S6 segmentectomy were successful, and the lesion in the right lung resolved after chemotherapy. Pathological examination showed that the resected lung had granulomas, infiltration of inflammatory cells, areas of necrosis, and a druse of Mucor in an abscess. We view this as a case of chronic necrotizing pulmonary mucormycosis.

Enhancing effects of unsaturated fatty acids with various structures on the permeation of indomethacin through rat skin.

Effects of straight-chain, cis-type, unsaturated fatty acids with various structures (alkyl chain lengths, numbers of double bonds, position of double bonds, and cis- and trans-positional isomers) on the skin permeation of indomethacin were examined by using rat skins in-vitro. Furthermore, the disordering degrees of the intercellular lipid domain in the stratum corneum, which were treated with preparations of unsaturated fatty acids, were measured by the Fourier transform infrared (FT-IR) method using excised rabbit ear skins. Unsaturated fatty acids enhanced the permeation of indomethacin through rat skins. These permeation-enhancing effects by unsaturated fatty acids were affected by changes of their alkyl chain length from C14 to C22. The lag-times on the permeation of indomethacin were shortened by unsaturated fatty acids in the following order: C20 = C18 = C22 < C16 < C14. These fluxes were increased by unsaturated fatty acids in the following order: C20 > C22 = C18 = C16 > C14. Therefore, gondoic acid (cis-11-eicosenoic acid; C20H38O2) mostly enhanced the skin permeation of indomethacin. However, the enhancing effects of unsaturated fatty acids (C18 chain) were not affected by their differences of position and numbers of double bonds. These permeation-enhancing effects which were evaluated by flux were related to the degrees of wave-number shift in the frequency of the antisymmetric CH bond stretching absorbance (near 2920 cm-1) on FT-IR spectra of the fatty acid-treated stratum corneum. Therefore, the perturbation increase of lipid domain in the stratum corneum by these fatty acids probably was the cause of the enhancing effects of permeation of indomethacin.

[Two cases of pneumonia caused by Sho-saiko-to].

We describe two cases of pneumonia caused by Sho-saiko-to. Patient 1 was a 61-year-old man with type-C liver cirrhosis. About 50 days after starting to take Sho-saiko-to, he complained of fever and diarrhea, and progressive dyspnea developed. Analysis of arterial blood obtained in the emergency room showed severe hypoxemia:, PaO2 26 Torr. A chest radiograph and a CT scan showed bilateral diffuse fine granular and ground-glass opacities predominantly in the upper lung fields. Despite repeated pulse therapy with methylprednisolone and aggressive medical treatment including mechanical ventilation, the patient remained in respiratory distress, which was later complicated by gastrointestinal bleeding. He died on the 45th hospital day. The bronchoalveolar lavage contained abnormally high fluid percents of lymphocytes and neutrophils. Postmortem examination of the lungs revealed alveolar septal thickening, marked hyperplasia of type 2 pneumocytes, and no hyaline membrane formation. Patient 2 was a 68-year-old man. Eighty days after he began taking Sho-saiko-to, he presented with a 4-day history of shortness of breath accompanied by fewer and progressive coughing. On arrival of the hospital, arterial blood gas analysis showed mild hypoxemia (PaO2, 61 Torr) and a chest radiograph revealed bilateral irregular infiltrates in the lower lung fields. Analysis of bronchoalveolar lavage fluid showed an abnormally high percent of lymphocytes (especially CD8 + lymphocytes), and examination of a biopsy specimen revealed exudates of fibrin and neutrophils in the alveolar spaces and patechy intraluminal organization. The response to prednisolone was good and he was discharged on the 40th hospital day in stable condition. Drug lymphocyte stimulation tests of peripheral blood to Sho-saiko-to were positive in both patients. Patients 2 was though to have a typical case of Sho-saiko-to-induced pneumonia, patient 1 was thought to have fulminating variant of this disease.

Interaction of serotonergic excitatory drive to hypoglossal motoneurons with carbachol-induced, REM sleep-like atonia.

The facilitatory effect of serotonin (5HT) on hypoglossal (XII) motoneurons is likely to be reduced during rapid eye movement (REM) sleep, when the activity of the brainstem serotonergic system reaches its nadir. Therefore, we assessed the hypothesis that application of exogenous 5HT will attenuate the REM sleep-like suppression of XII motoneurons produced in decerebrate cats by pontine microinjections of a cholinergic agonist, carbachol. Microinjections of 5HT or 5-carboxamidotryptamine into the XII nucleus increased XII nerve activity to 182 +/- 53% (standard deviation; SD) of control. Subsequent pontine microinjections of carbachol reduced XII nerve activity by 55 +/- 21% of the pre-5HT level (n = 12). Microinjections of methysergide (a 5HT antagonist) into the XII nucleus reduced XII nerve activity to 54 +/- 17% of the pre-methysergide control (n = 6). Pontine carbachol injections after methysergide further reduced XII nerve activity by 49 +/- 20% of the pre-methysergide level. Treatments with both agonists and the antagonist attenuated the carbachol-induced decrease when compared to two previous studies using the same model: 1) In experiments with no injections of serotonergic agents, pontine carbachol injections decreased XII nerve activity by 90 +/- 6% of control. 2) After enhancement of XII nerve activity by inhibitory amino acid antagonists (to 135 +/- 60%), the subsequent carbachol-induced decrease was even larger, 112 +/- 62% of control. We propose that serotonergic excitation can significantly attenuate the REM sleep-like suppression of XII nerve activity, and that this is achieved, in part, by substituting for the decreased endogenous 5HT in the XII nucleus. The study also demonstrates that other, non-serotonergic, mechanisms also contribute to the carbachol-induced suppression.

[Shortening of hospitalization period for patients with pulmonary tuberculosis].

The development of specific chemotherapeutic agents revolutionally improved the prognosis of tuberculosis and markedly shortened the duration of the treatment. Evidence of successful treatment with short-course regimens for pulmonary tuberculosis has been accumulated. But, the duration of hospitalization tends to be determined empirically and varys among hospitals and clinicians. Generally speaking, the duration of hospitalization is longer in Japan than in the United States and Europian countries. We investigated retrospectively the duration of hospitalization, treatment period, and recurrence rate of the disease for patients with pulmonary tuberculosis who admitted to the Tokyo Metropolitan Fuchu Hospital in the years 1984, 1988, and 1991. Patients who had been previously treated for more than 2 weeks and/or, had severe complications, such as malignancy and miliary tuberculosis were excluded from the study. Cases who died during the hospitalization and discharged without permission were also excluded. Numbers of subjects in each year were 114, 114, and 115 in 1984, 1988, and 1991, respectively. A total of 343 patients (M: 254, F: 89) were enrolled to the study and their average age was 49.4 yr old. A number of patients with both smear and culture positive in sputum bacteriology was 210 (61.2%), and 42 cases (12.2%) were smear negative and culture positive. The results are as follows: (1) Mean duration of hospitalization in the years 1984, 1988, and 1991 were 141, 102, and 72 days, respectively. That is, a mean hospitalization period was shortened to about half during these seven years. (2) According to the chest x-ray classification (Group A: I, II3, B: II1, II2, III3, C: III1, III2), mean durations of hospitalization were 186 days for group A, 143 days for group B, and 108 days for group C in 1984, and 96 days, 76 days, and 59 days in 1991, respectively. (3) According to sputum bacteriology, mean durations of hospitalization were 169 days for (S+/C+) cases, 105 days for (S-/C+) cases, and 90 days for (S-/C-) cases in 1984, and 83 days, 67 days, and 41 days in 1991, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)