Risk factors for postoperative nausea and vomiting after video-assisted thoracic surgery esophagectomy: a prospective cohort study.

Video-assisted thoracic surgery esophagectomy (VATS-E) may increase the risk of postoperative nausea and vomiting (PONV) because it uses a high dosage of anesthesia through a long operative duration. However, no study has examined the risk factors for PONV after VATS-E. Therefore, we investigated the risk factors for PONV to support the appropriate risk management of PONV after VATS-E. This prospective cohort study included 155 patients who underwent VATS-E at the Showa University Hospital between April 1st, 2020 and November 30th, 2022. The primary outcome was the incidence of PONV within 24 h after surgery. Significant independent risk factors associated with the incidence of PONV were selected using multivariate analysis. The association between the number of risk factors for PONV and incidence of PONV was analyzed. One-hundred fifty-three patients were included in the analysis. The patients' median age was 67 years (range, 44-88), and 79.1% were male. PONV occurred in 35 (22.9%) patients. In the multivariate analysis, remifentanil dosage > 89.0 ng/kg/ min, albumin ≤ 3.5 g/dL, and eGFR < 60 mL/min/1.73 m 2 were independent significant risk factors for PONV. A significant association was observed between the incidence of and the number of risk factors for PONV (0 factor, 5.8%; 1 factor, 27.3%; ≥ 2 factors, 40.0%; p = 0.001). These three risk factors are useful indicators for selecting patients at high risk of developing PONV after VATS-E. In these patients, avoiding the development of PONV will be possible by performing appropriate risk management.

The association between neutropenia and prognosis in stage III colorectal cancer patients receiving adjuvant chemotherapy.

Neutropenia during chemotherapy has been reported to be a predictor of better survival in patients with several types of cancer, although there are no reports on stage III colorectal cancer (CRC). The purpose of this study was to examine the association between neutropenia and prognosis in stage III CRC patients receiving adjuvant chemotherapy consisting of oral uracil and tegafur (UFT) plus leucovorin (LV). We retrospectively analysed 123 patients with stage III CRC who received UFT/LV as adjuvant chemotherapy. The end-point was disease-free survival (DFS). Survival curves of the two categories (neutropenia absent vs. present) were estimated using the Kaplan-Meier method and compared by the log-rank test. We estimated the hazard ratio (HR) for DFS according to neutropenia after adjustment for covariates by multivariate analyses using Cox's regression analysis. A total of 33 (26.8%) patients experienced neutropenia. Patients without neutropenia showed a significantly lower DFS than those with neutropenia (3-year DFS 57.3% vs. 81.2%, P = 0.0213). By multivariate analysis, neutropenia and histological type were independent prognostic factors, with HR of 0.410 (neutropenia absent vs. present, P = 0.045) and 4.793 (well to moderately differentiated vs. poorly differentiated, P = 0.004) respectively. We demonstrated that neutropenia occurring during adjuvant chemotherapy consisting of UFT/LV may be a prognostic factor of recurrence in stage III CRC patients.

Pth1r Signal in Gli1+ Cells Maintains Postnatal Cranial Base Synchondrosis.

Cranial base synchondroses are the endochondral ossification centers for cranial base growth and thus indispensable for proper skull, brain, and midfacial development. The synchondroses are composed of mirror-image growth plates that are continuously maintained from the embryonic to postnatal stage through chondrocyte differentiation. Several factors, including Pth1r signaling, are known to control fetal synchondrosis development. However, there are currently no reports regarding any role for Pth1r signaling in postnatal cranial base and synchondrosis development. Also, the mesenchymal cells that source Pth1r signaling for synchondroses are not known. Here, we employed an inducible mouse model, a hedgehog-responsive Gli1-CreERT2 driver, focusing on the postnatal study. We performed 2 inducible protocols using Gli1-CreERT2;Tomatofl/+ mice that uncovered distinct patterning of Gli1-positive and Gli1-negative chondrocytes in the synchondrosis cartilage. Moreover, we generated Gli1-CreERT2;Pth1rfl/fl;Tomatofl/+ mice to assess their functions in postnatal synchondrosis and found that the mutants had survived postnatally. The mutant skulls morphologically presented unambiguous phenotypes where we noticed the shortened cranial base and premature synchondrosis closure. Histologically, gradual disorganization in mutant synchondroses caused an uncommon remaining central zone between hypertrophic zones on both sides while the successive differentiation of round, flat, and hypertrophic chondrocytes was observed in control sections. These mutant synchondroses disappeared and were finally replaced by bone. Of note, the mutant fusing synchondroses lost their characteristic patterning of Gli1-positive and Gli1-negative chondrocytes, suggesting that loss of Pth1r signaling alters the distribution of hedgehog-responsive chondrocytes. Moreover, we performed laser microdissection and RNA sequencing to characterize the flat proliferative and round resting chondrocytes where we found flat chondrocytes have a characteristic feature of both chondrocyte proliferation and maturation. Taken together, these data demonstrate that Pth1r signaling in Gli1-positive cells is essential for postnatal development and maintenance in cranial base synchondroses. Our findings will elucidate previously unknown aspects of Pth1r functions in cranial biology and development.

An uncommon cleft subtype of unilateral cleft lip and palate.

The finding that the vomer plays a crucial role in maxillary growth suggests that the bilateral cleft configuration of unilateral cleft lip and palate (UCLP), in which the vomer is detached from the non-cleft-side secondary hard palate, negatively influences palatal development, and this hypothesis was tested. Sixty persons with complete UCLP, including those with the vomer detached from (n = 30, b-UCLP) and attached to (n = 30, u-UCLP) the secondary hard palate, were analyzed morphologically, with the use of cast models taken at 10 days, 3 mos, and 12 mos of age. The anterio-posterior palatal length at 12 mos of age in those with b-UCLP was significantly shorter than that in those with u-UCLP, by 8.7% (p < 0.05). In addition, palatal width development in the first year in those with b-UCLP was also significantly retarded. These results suggest that the uncommon bilateral cleft subtype in UCLP should be included in the cleft classification.

Nasolabial cyst in a patient with cleft lip and palate.

Nasolabial cysts are rare non-odontogenic cysts that occur beneath the ala nasi, and debate about their complicated, unique pathogenesis continues. It is widely accepted that these lesions originate from the anlage of the nasolacrimal duct; however, some still think that nasolabial cysts arise from fissural cysts. The authors report a patient with a nasolabial cyst who also had a unilateral cleft lip and palate. This unusual finding may indicate a different origin for nasolabial cysts than what has been accepted in the past.

Predictors of restenosis after coronary artery stenting.

AIM: The aim of this study was to analyze restenosis after percutaneous coronary intervention, factors related to restenosis after coronary artery stenting and the degree of the risk of restenosis were evaluated. METHODS: The study enrolled 181 patients (249 lesions) who underwent the first coronary artery stenting. Multivariate analysis was performed, and the restenotic index (RI) was calculated by combining the extracted predictors. RESULTS: Among the 181 patients (249 lesions), restenosis occurred in 89 (111 lesions) and did not occur in 92 (138 lesions). Vascular revasculation was performed in 95 restenosed target lesions in 68 patients. The mean period of follow-up angiography after the procedures was 206 days in the restenosis group and 271 days in the non-restenosis group, i.e. significantly shorter in the restenosis group. As a result of multivariate analysis, diabetes mellitus, Cr level, amount of the contrast medium used and stent diameter were selected as significant factors that independently contributed to the restenosis after coronary artery stenting. By combining these factors, the RI was calculated by the following formula for the prediction of restenosis: RI=exp (1.088xCr+0.909xdiabetes mellitus+0.871xcontrast medium+0.591xstent diameter). CONCLUSION: The risk of restenosis after coronary artery stenting can be predicted to an extent according to the RI devised in this study.

Clinical implications of taste thresholds in patients with odontogenic maxillary sinusitis.

Patients with odontogenic maxillary sinusitis (OMS) often complain of reduced taste sensitivity as well as nasal obstruction. The filter paper disc method (the conventional gustatory test) was applied to nine patients who underwent sinus surgery to open the inferior nasal meatus and sinus drainage, on three different days: 1day prior to surgery, 7days postoperative, and 28days postoperative. The same test was applied to nine non-clinical participants with or without clipping the nose to interfere with smooth nasal airflow on two different days. Acquired recognition thresholds for the four basic tastes of sweet, salty, sour, and bitter were assessed. In OMS patients, the recognition thresholds for all four tastes were markedly decreased at 7 and 28days postoperative, and subjective taste sensitivity and the elimination of nasal obstruction was improved. The mean recognition threshold for the four tastes correlated negatively with taste satisfaction scores. Clipping the nose in non-clinical participants induced increases in gustatory detection and recognition thresholds. Despite the small sample size and different ages and sexes of the study subjects, it was demonstrated that nasal obstruction in OMS patients and nose clipping in non-clinical subjects reduce taste reactivity, and surgical intervention to promote nasal airflow recovers impaired taste reactivity.

Inhibition of trigeminal respiratory activity by suckling.

UNLABELLED: The trigeminal motor system is involved in many rhythmic oral-motor behaviors, such as suckling, mastication, swallowing, and breathing. Despite the obvious importance of functional coordination among these rhythmic activities, the system is not well-understood. In the present study, we examined the hypothesis that an interaction between suckling and breathing exists in the brainstem, by studying the respiratory activity in trigeminal motoneurons (TMNs) during fictive suckling using a neonatal rat in vitro brainstem preparation. The results showed that fictive suckling, which was neurochemically induced by bath application of N-methyl-D,L-aspartate and bicuculline-methiodide, or by local micro-injection of the same drugs to the trigeminal motor nucleus, inhibited the inspiratory activities in both respiration TMNs and respiratory rhythm-generating neurons. Under patch-clamp recording, fictive suckling caused membrane potential hyperpolarization of respiration TMNs. We conclude that the brainstem preparation contains an inhibitory circuit for respiratory activity in the trigeminal motor system via the rhythm-generating network for suckling. ABBREVIATIONS: BIC, bicuculline methiodide; GABA, gamma aminobutyric acid; NMA, N-methyl-D,L-aspartate; NMDA, N-methyl-D-aspartate; and TMN, trigeminal motoneuron.

Spheric mass beneath the alar base: MR images of nasolabial cyst and schwannoma.

We report 2 cases of nasolabial cyst and a case of schwannoma beneath the alar base that required a differential diagnosis because of clinical features and MR images that resembled the nasolabial cyst. The morphologic analysis on MR images revealed the characteristic appearance of the nasolabial cyst, and the sagittal MR image may be most helpful for diagnosing this rare disease.

Evaluation of paraumbilical vein as a prognostic index of severe liver cirrhotic patients with portal-systemic shunts.

AIM: The aim of this study was to predict the outcome in severe liver cirrhotic patients with portal-systemic shunts. METHODS: One-hundred and sixteen patients with liver cirrhosis diagnosed as Child-Pugh class B and C with portal-systemic shunts confirmed by abdominal ultrasonography, computed tomography and magnetic resonance imaging were enrolled in this study. Twenty-three factors were evaluated concerning clinical laboratory parameters and extracted prognostic factors using the Cox proportional hazards model, and the prognostic index (PI) was prepared by combining these factors. RESULTS: The cumulative survival rates after admission were 64.6%, 35.6% and 25% after 1, 3 and 5 years, respectively. Using multivariate analysis, age, the presence of hepatocellular carcinoma (HCC), portal vein tumor thrombosis (PVTT) and paraumbilical vein (PUV) shunt were selected as significant prognostic factors that contributed independently to the prognosis of severe liver cirrhotic patients with portal-systemic shunts. The PI was calculated with the following formula using these 4 factors. PI = 0.042 x Age + 0.913 x HCC + 0.989 x PVTT + 1.079 x PUV shunt. The group with a high score for PI was found to die with significantly higher frequency than the group with a low score. CONCLUSIONS: It was found that tumor related factors and PUV shunt were the most important factors for severe liver cirrhotic patients with portal-systemic shunts. The PI is suggested to be an appropriate index to predict the prognosis for these patients.

Prognostic factors of primary biliary cirrhosis detected by health screening.

AIM: The liver cirrhosis is likely to differ in the Japanese and Western populations. Thus, we performed a retrospective cohort analysis by a review of clinical records to clarify prognostic factors after the onset of primary biliary cirrhosis (PBC) detected by health screening. METHODS: The subjects were 52 patients with PBC. Thirty-nine factors were evaluated concerning clinical data and extracted prognostic factors using the Cox proportional hazard model. RESULTS: The mean duration of the follow-up period was 5.1 years, during which 6 (11.5%) of the patients died. The cumulative survival rate after the onset of PBC was 93.4% after 5 year, and 67.8% after 10 years. Multivariate analysis indicated 2 factors, i.e. the body mass index (BMI), and IgG, as independent prognostic factors. Their hazard ratios were 0.399 (per 1 kg/m2 of BMI) and 1.282 (per 100 mg/dL of IgG). The prognostic index (PI) was calculated by the following formula using these 2 factors. PI = 0.919 x BMI+0.249 x IgG. CONCLUSIONS: The prediction of the outcome using PI based on the 2 factors provides additional information for the determination of the therapeutic approach in PBC after health screening.

IL-12 plays a pivotal role in LFA-1-mediated T cell adhesiveness by up-regulation of CCR5 expression.

The chemokine receptor CCR5 has been implicated in the recruitment of T cells to inflammatory sites. However, the regulation of CCR5 induction on T cells and its contribution to T cell adhesiveness are poorly understood. Using a Th1 clone, 2D6, that can be maintained with interleukin (IL)-12 or IL-2 alone (designated 2D6(IL-12) or 2D6(IL-2), respectively), we investigated how CCR5 is induced on T cells and whether CCR5 is responsible for up-regulating the function of adhesion molecules. 2D6(IL-12) grew, forming cell aggregates, in culture containing IL-12. This was due to lymphocyte function-associated antigen (LFA)-1-intercellular adhesion molecule (ICAM)-1 interaction, because 2D6(IL-12) expressed both LFA-1 and ICAM-1 and cell aggregation was inhibited by anti-ICAM-1 monoclonal antibody. Despite comparable levels of LFA-1 and ICAM-1 expression, 2D6(IL-2) cells did not aggregate in culture with IL-2. It is important that there was a critical difference in CCR5 expression between 2D6(IL-12) and 2D6(IL-2); the former expressed high levels of CCR5, and the latter expressed only marginal levels. Both types of cells expressed detectable albeit low levels of RANTES (regulated on activation, normal T expressed and secreted) mRNA. Unlike IL-12 or IL-2, IL-18 induced high levels of RANTES mRNA expression without modulating CCR5 expression. Therefore, combined stimulation with IL-12 and IL-18 strikingly up-regulated 2D6 cell aggregation. Notably, LFA-1-mediated aggregation of 2D6(IL-12) cells was suppressed by anti-CCR5 antibody. These results indicate that IL-12 plays a critical role in CCR5 expression on Th1 cells and consequently contributes to CCR5-mediated activation of LFA-1 molecules.

Temporal patterns of trigeminal respiratory activity in rat brainstem-spinal cord in vitro.

Respiratory activity in trigeminal (V) motoneurons was studied in rhythmically active en bloc brainstem-spinal cord preparations isolated from neonatal rats (P0-P3). In the majority of preparations (83%), the temporal pattern of V activity consisted of spontaneous inspiratory phasic discharge with onset delayed or coincident with onset of phrenic motoneuron discharge. Blockade of alpha-2 noradrenergic receptor activation shifted onset of V respiratory discharges earlier than phrenic discharges, while elevation of extracellular potassium concentration or blockade of GABAergic and glycinergic inhibitory synaptic transmission had little effect on temporary pattern of V respiratory discharges. We conclude V motoneurons in the in vitro preparation generate respiratory activity during inspiratory phase, and their temporal patterns are modulated by inhibitory noradrenergic synaptic transmission.

Localization of oral-motor rhythmogenic circuits in the isolated rat brainstem preparation.

Using an in vitro isolated brainstem preparation from neonatal rat (0-2 days), the minimal circuitry for production of rhythmical oral-motor activity was determined. In the presence of the excitatory amino acid agonist, N-methyl-D,L-aspartate (NMA), and the GABAA antagonist, bicuculline (BIC), rhythmical oral-motor activity was recorded from the motor branch of the trigeminal nerve. In preparations where the brainstem was isolated in continuity between the rostral inferior colliculus and the obex, oral-motor activity was not observed. However, when the brainstem was serially transected in the coronal plane starting at the obex and proceeding rostrally, rhythmogenic activity emerged and became more stable until the level of the rostral facial nucleus (facial colliculus, FC) was approached. Transections more rostral than the FC produced rhythms that progressively deteriorated until the trigeminal motor nucleus (MoV) was reached, at which point all activities ceased. Surgical isolation of an ipsilateral quadrant of the brainstem encompassing the tissue between the FC and inferior colliculus, rostro-caudally, and the midline to lateral brainstem, medio-laterally, exhibited oral-motor activity as well. The remaining contralateral side of brainstem was devoid of rhythmical trigeminal activity. However, further coronal transection of the remaining brainstem at the level of the FC induced rhythmical oral-motor activity in the trigeminal nerve. The data suggest the existence of bilaterally coordinated rhythmogenic circuits in each half of brainstem between the rostral trigeminal nucleus and the rostral facial nucleus, which are tonically inhibited by brainstem circuits caudal to the facial nucleus.

Effect of lung inflation on levator veli palatini muscle activity.

Palatal movements play a critical role in regulating oropharyngeal airflow during breathing. We hypothesized that these movements are coordinated with breathing movements via afferent signals from the lung. However, the control of palatal movements in relation to the lung remains unclear. This study was designed to define, by electromyographic techniques, the relationship between palatal movement and lung action during respiration. We performed tracheotomies on 12 mongrel dogs anesthetized with sodium pentobarbital and found that lung inflation augmented the activity of the levator veli palatini muscle (LVP). Two kinds of discharges were recognized during the expiratory pause following lung inflation. One was a continuous, low-amplitude discharge induced during apnea following lung inflation. The other was a transient, high-amplitude discharge which appeared immediately after lung inflation. Both of these response activities were eliminated by bilateral vagotomy. We thus concluded that palatal movements, which can regulate expiratory airflow resistance and cause switching from nasal to oral airflow, are under the control of vagal afferent signals from the lung.

Measurement of velopharyngeal movements induced by isolated stimulation of levator veli palatini and pharyngeal constrictor muscles.

The levator veli palatini (LVP) and superior pharyngeal constrictor muscles (PC) close the velopharynx. However, for the velopharyngeal movements to be understood in detail, each muscle contraction must be analyzed precisely. This study was performed to clarify the velopharyngeal movement which was induced by a single muscle contraction, LVP or PC. Using a nasopharyngeal fiberscope, we analyzed the velopharyngeal movement associated with the contraction of the LVP and PC muscles in mongrel dogs. To elicit the maximal contraction of each muscle, we applied repetitive electrical stimulation to each peripheral nerve efferent to the LVP or PC muscle. Stimulation with a frequency of 77 Hz and 83 Hz induced maximal tension in the LVP and PC muscles, respectively, in isometric contraction. In a second series of experiments, fiberscopic views of the velopharyngeal movements associated with each muscle's maximal contraction were recorded. The degree of closure was calculated at several sections. The LVP muscle pulled the caudal fourth of the soft palate, while the PC projected the posterior wall at the level of the caudal end of the soft palate. The PC muscle also projected the lateral wall of the velopharynx. The effect of LVP contraction on the lateral wall was very small. These results show that the velopharyngeal movement associated with LVP contraction is very different from that with PC contraction.

Effect of serotonin (5-HT) on trigeminal rhythmic activities generated in in vitro brainstem block preparations.

We used rat isolated brainstem block preparations to analyze the functional roles of serotonin receptors in the generation of trigeminal rhythmic activities. We previously reported that trigeminal rhythmic activities could be induced by some pharmacological applications in an isolated brainstem preparation with a rostral boundary at the border between the inferior and superior colliculus, and a caudal border at the level of the rostral facial nucleus. However, the same stimulation did not induce trigeminal rhythmic activities in a whole brainstem block preparation with the same rostral boundary and a caudal border at the obex level. In the present study, both the 5-HT(1A) phthalimido-butyl-piperazine, and the 5-HT(2C) agonist, 1-2,5-dimethoxy-4-iodophenyl-2-aminopropane, combined with N-methyl-D,L-aspartate and bicuculline, elicited trigeminal rhythmic activities in a whole brainstem block preparation. Our results suggest that serotonin has both facilitation and inhibition effects on the generation of trigeminal rhythmic activities in an isolated brainstem block preparation in vitro.

The innervation of the levator veli palatini muscle by the glossopharyngeal nerve.

We developed a novel method which enables bloodless exposure of the levator veli palatini muscle in rat in order to investigate the physiological properties of this muscle. The levator veli palatini muscle which is innervated by a branch of the glossopharyngeal nerve showed rhythmic spontaneous movement in rats. Cutting the branch supplying LVP of the glossopharyngeal nerve caused cessation of the spontaneous movement of the levator veli palatini muscle. The spontaneous discharges of the glossopharyngeal nerve were synchronized with those of the phrenic nerve. A mixture of 95% oxygen and 5% room air influenced the efferent discharges from the branch of the glossopharyngeal nerve supplying the levator veli palatini muscle. These findings indicate that the motor nerve supply to the levator veli palatini muscle is the glossopharyngeal nerve, and the levator veli palatini muscle is related to the respiratory system, in particular with inspiration in rats.

Effect of norepinephrine receptors on trigeminal rhythm generation in newborn rats.

N-methyl-D,L-aspartate acid and bicuculline are required to enhance the trigeminal rhythmic activities in an in vitro isolated brainstem block preparation. In this study, we analyzed the effect of norepinephrine on the trigeminal neural circuit underlying rhythmic jaw movements. Rhythmic trigeminal activity is observed in brainstem preparations (inferior colliculus to obex) only following blockade of alpha(2)-adrenoceptors with idazoxan. This observation, combined with the inhibition of rhythm by alpha(2)-adrenoceptor agonists suggests endogenous alpha(2)-adrenoceptor mediated inhibition of trigeminal networks. A complex noradrenergic modulation of trigeminal systems is further supported by the prazosin-sensitive potentiation of rhythm by bath application of the alpha(1)-adrenoceptor agonist phenylephrine.

Migration of a dental implant into the maxillary sinus. A case report.

This article reports a rare case of a displaced dental implant that migrated into the maxillary sinus.