Denosumab-induced hypocalcemia in patients with solid tumors and renal dysfunction: a multicenter, retrospective, observational study.

BACKGROUND: Bone metastases are frequently observed in advanced cancer, and bone modifying agents are used to prevent or treat skeletal-related events. Zoledronic acid is contraindicated in patients with severe renal impairment (Ccr < 30 mL/min), but it is not completely known whether denosumab can be used in them. We aimed to determine the association between renal function and hypocalcemia development during denosumab treatment. METHODS: We included patients with solid cancer and bone metastases who started denosumab treatment between April 2017 and March 2019. They were classified into four groups based on creatinine clearance (Ccr; mL/min): normal (Ccr ≥ 80), mild (50 ≤ Ccr ˂80), moderate (30 ≤ Ccr ˂50), and severe (Ccr ˂30). Hypocalcemia was evaluated using the Common Terminology Criteria for Adverse Events (v5.0) based on the albumin-adjusted serum calcium levels; its incidence (stratified by renal function) and risk factors were investigated using a Chi-square test and logistic regression analysis. RESULTS: Of 524 patients (age: 69 ± 11 years; 303 men), 153 had a normal renal function and 222, 117, and 32 had mild, moderate, and severe renal dysfunction. The albumin-adjusted serum calcium level was higher than the measured (total) calcium level in most patients. The incidence of grade ≥ 1 hypocalcemia was 32.0% in the normal group and 37.4%, 29.9%, and 62.5% in the mild, moderate, and severe renal dysfunction groups, respectively. It was, therefore, higher in the severe renal dysfunction groups than in the normal group (P = 0.002). The incidence of grade ≥ 3 hypocalcemia did not differ significantly among the groups. Pre-treatment low serum calcium levels and severe renal dysfunction were risk factors for hypocalcemia. CONCLUSIONS: Evaluating denosumab-induced hypocalcemia required albumin adjustment, and its incidence was high among patients with severe renal dysfunction. Reduced serum calcium levels and severely impaired renal function were associated with an elevated hypocalcemia risk.

Mutational analysis of DNMT3A improves the prognostic stratification of patients with acute myeloid leukemia.

Nucleophosmin1 (NPM1) mutations are the most frequently detected gene mutations in acute myeloid leukemia (AML) and are considered a favorable prognostic factor. We retrospectively analyzed the prognosis of 605 Japanese patients with de novo AML, including 174 patients with NPM1-mutated AML. Although patients with NPM1-mutated AML showed a high remission rate, this was not a favorable prognostic factor for overall survival (OS); this is contrary to generally accepted guidelines. Comprehensive gene mutation analysis showed that mutations in codon R882 of DNA methyltransferase 3A (DNMT3AR882 mutations) were a strong predicative factor indicating poor prognosis in all AML (p < 0.0001) and NPM1-mutated AML cases (p = 0.0020). Furthermore, multivariate analysis of all AML cases showed that DNMT3AR882 mutations and the co-occurrence of internal tandem duplication in FMS-like tyrosine kinase 3 (FLT3-ITD), NPM1 mutations, and DNMT3AR882 mutations (triple mutations) were independent factors predicting a poor prognosis related to OS, with NPM1 mutations being an independent factor for a favorable prognosis (hazard ratios: DNMT3AR882 mutations, 1.946; triple mutations, 1.992, NPM1 mutations, 0.548). Considering the effects of DNMT3AR882 mutations and triple mutations on prognosis and according to the classification of NPM1-mutated AML into three risk groups based on DNMT3AR882 /FLT3-ITD genotypes, we achieved the improved stratification of prognosis (p < 0.0001). We showed that DNMT3AR882 mutations are an independent factor for poor prognosis; moreover, when confounding factors that include DNMT3AR882 mutations were excluded, NPM1 mutations were a favorable prognostic factor. This revealed that ethnological prognostic discrepancies in NPM1 mutations might be corrected through prognostic stratification based on the DNMT3A status.

Evaluation and Prediction of Healing Morphology After Closed Reduction for Unilateral Mandibular Condyle Fractures.

Although closed reduction is common for condylar fractures, bone fragments may heal improperly. This study aimed to investigate the healing morphology of unilateral condylar fractures. We retrospectively investigated 70 patients with unilateral condylar fractures. Clinico-statistical analyses were performed on the whole-condylar fracture, closed reduction, and observation/functional therapy groups. Among these patients, 52 patients aged older than 16 years underwent closed reduction. The extent of maximum mouth opening, the incidence of malocclusion, and the relationship between healing morphology and Arbeitsgemeinschaft für Osteosynthesefragen classification or trismus were analyzed in the closed reduction group. There were significant differences in age ( P= 0.008) and sex ( P =0.025) between the closed reduction and observation/functional therapy groups. However, there were no significant differences in trauma etiologies and concomitant fractures between the 2 groups. The average maximum mouth opening extent for unilateral fractures after closed reduction was 42.6±6.1 mm. Only 1 case (2.1%) of post-treatment malocclusion was observed. In all the MacLennan classification of deviation or more, regardless of the classification, upper fractures (head and upper neck) tended to heal through a spherical ( P <0.001) morphology, whereas lower fractures (lower neck and subcondylar) tended to heal through an L-shaped and lateral fusion ( P <0.001). There was no significant difference in the incidence of trismus between the healing morphology of unchanged type and others ( P =0.690). Our results elucidated the etiology, dysfunction, and healing morphology classification of unilateral mandibular condyle fractures treated with closed reduction.

Risk factors for recurrence and regrowth of spinal schwannoma.

BACKGROUND: Spinal schwannoma recurs after initial surgery at a rate of 4%-6%, with known risk factors including subtotal resection, multilevel involvement, large tumor size, and malignant histopathology. This study examined risk factors for schwannoma recurrence and residual tumor regrowth. METHODS: Sixty-five patients who underwent resection of spinal schwannoma in our department between July 2010 and December 2018 and were followed up for more than 1 year were retrospectively analyzed for age, sex, follow-up duration, imaging and surgical data, recurrence, reoperation, and Japanese Orthopaedic Association scores before and 1 year after surgery. Patients with postoperative recurrence or residual tumor regrowth of >10% at the final visit (R+ group) were compared with patients without recurrence or regrowth (R- group). Multivariate logistic regression analysis was performed to analyze concurrent effects of risk factors on recurrence and regrowth. RESULTS: The 65 patients (mean age 52.4 years at surgery) had schwannomas involving cervical (n = 14), thoracic (n = 25), and lumbar (n = 26) spinal levels. Mean follow-up duration was 58 months. Location was intradural in 65%, extradural in 17%, and both intradural and extradural in 18%. There were 4 recurrences (6.2%), and the mean interval between surgery and recurrence was 18.8 months. Seven patients (10.8%) experienced regrowth. Comparing group R+ (n = 11) and group R- (n = 54), univariate analysis showed significant differences in Sridhar tumor classification, giant tumor (Sridhar classification II, IVb, and V), left-right and cranial-caudal tumor size, largest diameter, operative time, blood loss, subtotal resection, reoperation, fusion surgery, and follow-up duration. Multivariate logistic regression analysis revealed giant tumor (Sridhar classification types II, IVb, and V) as an independent risk factor for recurrence and regrowth. CONCLUSIONS: This retrospective review of 65 consecutive patients with spinal schwannoma in a single institution demonstrated that 16.9% had recurrence or regrowth, demonstrating that this potential risk should be kept in mind.

Multifocal intraoral ductal ectasia with metaplasia and focal epithelial proliferation: A case report.

Ductal ectasia with metaplasia and focal epithelial proliferation in the oral cavity does not correspond to any existing salivary gland lesion. A 72-year-old man presented with a mass in the buccal mucosa, which was excised and initially diagnosed as a cystadenoma. An upper lip mass on the right side, which developed later, was also excised. The lesions were histologically similar, and since they were multifocal and in non-contiguous and independent sites with multiple dilated cystic structures that did not destroy the lobar architecture, the final diagnosis was confirmed as ductal ectasia with metaplasia and focal epithelial proliferation. This condition may mimic various neoplastic lesions.

[Effect of Landiolol for Atrial Fibrillation after Open Heart Surgery].

PURPOSE: Postoperative atrial fibrillation (POAF) after open heart surgery is common complication. POAF is reported to prolong hospital stay and increase long-term mortality, therefore prevention of POAF is important. It is widely known that beta blocker decrease POAF, and we had used oral beta blocker after open heart surgery. We examined the effect of intraoperative and postoperative administration of intravenous beta blocker( landiolol) for POAF. METHOD: We evaluated 291 consecutive patients who underwent open heart surgery from November 2016 to November 2018. Those who underwent open heart surgery after November 2017 were 145, and 100 of the patients( group A) had intraoperative and postoperative landiolol administration. Those who underwent open heart surgery before November 2017 were 146, and 100 of the patients (group B) did not have landiolol administration. The primary endpoint was incidence of POAF within 7 days after surgery. RESULT: There was no significant difference in preoperative character between the groups, other than the ratio of males to females( group A:54 males, 46 females;group B:68 males, 32 females;p<0.05). The incidences of POAF were 20% and 36% in group A and group B, respectively( p<0.05). CONCLUSION: Intraoperative and postoperative administration of landiolol is effective for preventing POAF after open heart surgery.

[A Useful Case of Coronary Angiography during Surgery for Coronary Aneurysms:Report of a Case].

Coronary artery aneurysm with fistula is a relatively rare disease. After surgery, residual coronary fistula is often a problem. To prevent these problems, we perform coronary angiography during surgery, and have good grades. A 70-year-old-woman was admitted to our hospital with a chief complaint of palpitations. Enhanced computed tomography (CT) showed coronary aneurysms. Coronary angiography confirmed the coronary artery aneurysms with fistula to the pulmonary artery. Surgical intervention in the hybrid operating room was performed through median sternotomy with cardiopulmonary bypass. The fistulae were ligated, and the aneurysms were resected. Finally, coronary angiography was performed to confirm that there were no residual shunt aneurysm, or damage to the normal coronary artery, and the operation was completed. Postoperative course was uneventful, and she was discharged on postoperative day 19. Performing coronary angiography during surgery is very useful to confirm the aneurysms are completely closed, coronary artery fistulae are treated, and the coronary arteries are undamaged.

Time to extinction of a cultural trait in an overlapping generation model.

How long a newly emerging trait will stay in a population is a fundamental but rarely asked question in cultural evolution. To tackle this question, the distribution and mean of the time to extinction of a discrete cultural trait are derived for models with overlapping generations, in which trait transmission occurs from multiple role models to a single newborn and may fail with a certain probability. We explore two models. The first is a Moran-type model, which allows us to derive the exact analytical formula for the mean time to extinction of a trait in a finite population. The second is a branching process, which assumes an infinitely large population and allows us to derive approximate analytical formulae for the distribution and mean of the time to extinction in the first model under a large population size. We show that in the first model, the mean time to extinction apparently diverges (becomes so large that even numerical computation is impractical) under a certain parameter condition as the population size tends to infinity. Using the second model, we explain the underlying mechanism of the apparent divergence found in the first model and derive the mathematical condition for this divergence in terms of transmission efficiency and the number of role models per newborn. When this mathematical condition is satisfied in the second model, the probability of extinction is less than 1, and the mean extinction time does not exist. In addition, we find that in both models, the time to extinction of the trait becomes longer as the number of role models per individual increases and as cultural transmission becomes more efficient.

Application of an index derived from the area under a neutrophil curve as a predictor of surgical site infection after spinal surgery.

BACKGROUND: Patients with prolonged and intense neutrophilia after spinal surgery are at high risk of developing surgical site infection (SSI). To date, there is no standard method for the objective assessment of the intensity and duration of neutrophilia. Thus, this retrospective observational study aimed to test a new index (I-index), developed by combining the duration and intensity of neutrophilia, as a predictor of SSI. METHODS: I-index was calculated based on the postoperative neutrophil percentage. A total of 17 patients with SSI were enrolled as cases, and 51 patients without SSI were selected as controls. The groups were matched at a ratio of 1:3 by age, sex, and surgery type. The differences in the I-index were compared between the groups. Moreover, we checked the cumulative I-index (c-I-index), which we defined as the area under the neutrophil curve from postoperative day 1 until the first clinical manifestation of SSI in each case. Furthermore, a cutoff for SSI was defined using the receiver operating characteristic curve. RESULTS: The median I-index-7, I-index-14, and c-I-index were significantly higher in the SSI group than those in the control group. For a cutoff point of 42.1 of the I-index-7, the sensitivity and specificity were 0.706 and 0.882, respectively. For a cutoff point of 45.95 of the I-index-14, the sensitivity and specificity were 0.824 and 0.804, respectively. For a cutoff point of 45.95 of the c-I-index, the sensitivity and specificity were 0.824 and 0.804, respectively. CONCLUSION: We devised a new indicator of infection, i.e., the I-Index and c-I-index, and confirmed its usefulness in predicting SSI.

[On-pump Beating Pulmonary Embolectomy for Acute Pulmonary Thromboembolism].

BACKGROUND: Acute massive pulmonary embolism is a life-threatening disease and the reported rate of mortality is 52%.It is often treated with anticoagulation therapy or thrombolysis, but in case of critically ill patients with shock or cardiac arrest, its effect is limited. Surgical embolectomy is a treatment option for patients with hemodynamic instability. We studied the outcomes of our patients who underwent on-pump beating pulmonary embolectomy for acute pulmonary embolism. METHOD: We evaluated eight consecutive patients who underwent on-pump beating pulmonary embolectomy for acute pulmonary embolism since May 2012 to September 2016. Our surgical indications were hemodynamic instability, but one patient underwent pulmonary embolectomy without hemodynamic instability because the patient had floating thrombus in the right heart. Three patients experienced cardiac arrest, and two patients were treated with extracorporeal membrane oxygenation (ECMO). Four patients were treated with thrombolysis before surgical embolectomy. RESULT: All patients underwent on-pump beating pulmonary embolectomy. One patient could not be weaned from cardiopulmonary bypass, and was treated with ECMO after pulmonary embolectomy. The patient died due to low output syndrome, while the other seven patients were rescued. One patient had gastrointestinal bleeding after surgery, but the other patients had developed no major complication including thrombosis, hemorrhage, and prolonged respiratory failure during follow-up of 11.4±16.1 months. CONCLUSION: Pulmonary embolectomy is effective treatment for acute massive pulmonary embolism. On-pump beating pulmonary embolectomy is useful surgical procedure. Acute pulmonary embolism is often treated with anticoagulation therapy or thrombolysis, but in critically ill patients, surgical pulmonary embolectomy should be considered.

The popularity spectrum applied to a cross-cultural question.

We investigate a new approach for identifying the contribution of horizontal transmission between groups to cross-cultural similarity. This method can be applied to datasets that record the presence or absence of artefacts, or attributes thereof, in archaeological and ethnographic assemblages, from which popularity spectra can be constructed. Based on analytical and simulation models, we show that the form of such spectra is sensitive to horizontal transmission between groups. We then fit the analytical model to existing datasets by Bayesian MCMC and obtain evidence for strong horizontal transmission in oceanic as opposed to continental datasets. We check the validity of our statistical method by using individual-based models, and show that the vertical transmission rate tends to be underestimated if the datasets are obtained from lattice-structured rather than island-structured meta-populations. We also suggest that there may be more borrowing of functional than stylistic traits, although the evidence for this is currently ambiguous.

Relationship between pharyngeal airway depth and ventilation condition in mandibular setback surgery: A computational fluid dynamics study.

OBJECTIVES: This study aimed to determine the anteroposterior depth (APD) of the pharyngeal airway (PA) where post-operative PA obstruction was predicted, using computer fluid dynamics (CFD), in order to prevent obstructive sleep apnoea after mandibular setback surgery. SETTINGS AND SAMPLE POPULATION: Nineteen skeletal Class III patients (8 men; mean age, 26.7 years) who required mandibular setback surgery had computed tomography images taken before and 6 months after surgery. METHODS: The APD of each site of the four cross-sectional reference planes (retropalatal airway [RA], second cervical vertebral airway, oropharyngeal airway and third cervical vertebral airway) were measured. The Maximum negative pressure (Pmax) of the PA was measured at inspiration using CFD, based on a three-dimensional PA model. Intersite differences were determined using analysis of variance and the Friedman test with Bonferroni correction. The relationship between APD and Pmax was evaluated by Spearman correlation coefficients and non-linear regression analysis. RESULTS: The smallest PA site was the RA. Pmax was significantly correlated with the APD of the RA (rs  = .628, P < .001). The relationship between Pmax and the APD-RA was fitted to a curve, which showed an inversely proportional relationship of Pmax to the square of the APD-RA. Pmax substantially increased even with a slight reduction of the APD-RA. In particular, when the APD-RA was 7 mm or less, Pmax increased greatly, suggesting that PA obstruction was more likely to occur. CONCLUSIONS: The results of this study suggest that APD-RA is a useful predictor of good PA ventilation after surgery.

Loss of cyclin-dependent kinase 1 impairs bone formation, but does not affect the bone-anabolic effects of parathyroid hormone.

Bone mass is maintained by a balance between osteoblast-mediated bone formation and osteoclast-mediated bone resorption. Although recent genetic studies have uncovered various mechanisms that regulate osteoblast differentiation, the molecular basis of osteoblast proliferation remains unclear. Here, using an osteoblast-specific loss-of-function mouse model, we demonstrate that cyclin-dependent kinase 1 (Cdk1) regulates osteoblast proliferation and differentiation. Quantitative RT-PCR analyses revealed that Cdk1 is highly expressed in bone and is down-regulated upon osteoblast differentiation. We also noted that Cdk1 is dispensable for the bone-anabolic effects of parathyroid hormone (PTH). Cdk1 deletion in osteoblasts led to osteoporosis in adult mice due to low bone formation, but did not affect osteoclast formation in vivo Cdk1 overexpression in osteoblasts promoted proliferation, and conversely, Cdk1 knockdown inhibited osteoblast proliferation and promoted differentiation. Of note, we provide direct evidence that PTH's bone-anabolic effects occur without enhancing osteoblast proliferation in vivo Furthermore, we found that Cdk1 expression in osteoblasts is essential for bone fracture repair. These findings may help reduce the risk of nonunion after bone fracture and identify patients at higher risk for nonresponse to PTH treatment. Collectively, our results indicate that Cdk1 is essential for osteoblast proliferation and that it functions as a molecular switch that shifts osteoblast proliferation to maturation. We therefore conclude that Cdk1 plays an important role in bone formation.

Evolution of cumulative culture for niche construction.

A mathematical model of the joint evolution of learning and niche construction in a spatially subdivided population is described, in which culture is used to practice niche construction and can evolve by accumulating small improvements over generations. Individuals allocate their lifetimes to social learning, individual learning, niche construction to improve the environment, and exploitation of resources according to their genetically determined strategies. The coordinated optimal strategy (COS) is defined as the allocation strategy which maximizes the equilibrium fecundity of the population, as opposed to the convergence stable strategy (CSS), which is the strategy favored by natural selection. Both the COS and CSS are analytically derived and compared. It turns out that, although the levels of the CSS in terms of culture and the environmental quality can be high in a highly viscous population, they are in general much lower than those of the COS. It is argued that the discrepancy between the CSS and COS stems from the producer-scrounger structure inherent in the model. Analysis of transient dynamics reveals that the level of culture and the environmental quality may temporarily undergo drastic increases after sudden changes in parameter values, although they eventually drop down to low values due to the genetic adaptation of the time allocation strategy to the new cultural and environmental backgrounds. Implications of the results for human evolution are discussed.

Usefulness of BCOR gene mutation as a prognostic factor in acute myeloid leukemia with intermediate cytogenetic prognosis.

BCOR gene is a transcription regulatory factor that plays an essential role in normal hematopoiesis. The wider introduction of next-generation sequencing technology has led to reports in recent years of mutations in the BCOR gene in acute myeloid leukemia (AML), but the related clinical characteristics and prognosis are not sufficiently understood. We investigated the clinical characteristics and prognosis of 377 de novo AML cases with BCOR or BCORL1 mutation. BCOR or BCORL1 gene mutations were found in 28 cases (7.4%). Among cases aged 65 years or below that were also FLT3-ITD-negative and in the intermediate cytogenetic prognosis group, BCOR or BCORL1 gene mutations were observed in 11% of cases (12 of 111 cases), and this group had significantly lower 5-year overall survival (OS) (13.6% vs. 55.0%, P = 0.0021) and relapse-free survival (RFS) (14.3% vs. 44.5%, P = 0.0168) compared to cases without BCOR or BCORL1 gene mutations. Multivariate analysis demonstrated that BCOR mutations were an independent unfavorable prognostic factor (P = 0.0038, P = 0.0463) for both OS and RFS. In cases of AML that are FLT3-ITD-negative, aged 65 years or below, and in the intermediate cytogenetic prognosis group, which are considered to have relatively favorable prognosis, BCOR gene mutations appear to be an important prognostic factor.

Genealogies and ages of cultural traits: An application of the theory of duality to the research on cultural evolution.

A finite-population, discrete-generation model of cultural evolution is described, in which multiple discrete traits are transmitted independently. In this model, each newborn may inherit a trait from multiple cultural parents. Transmission fails with a positive probability unlike in population genetics. An ancestral process simulating the cultural genealogy of a sample of individuals is derived for this model. This ancestral process, denoted by M-, is shown to be dual to a process M+ describing the change in the frequency of a trait. The age-frequency spectrum is defined as a two-dimensional array whose (i,k) element is the expected number of distinct cultural traits introduced k generations ago and now carried by i individuals in a sample of a particular size n. Numerical calculations reveal that the age-frequency spectrum and related metrics undergo a critical transition from a phase with a moderate number of young, rare traits to a phase with numerous very old, common traits when the expected number of cultural parents per individual exceeds one. It is shown that M+ and M- converge to branching or deterministic processes, depending on the way population size tends to infinity, and these limiting processes bear some duality relationships. The critical behavior of the original processes M+ and M- is explained in terms of a phase transition of the branching processes. Using the results of the limiting processes in combination, we derive analytical formulae that well approximate the age-frequency spectrum and also other metrics.

Full-length mutation search of the TP53 gene in acute myeloid leukemia has increased significance as a prognostic factor.

TP53 gene abnormality has been reported to be an unfavorable prognostic factor in acute myeloid leukemia (AML). However, almost all studies of TP53 gene abnormality so far have been limited to mutation searches in the DNA binding domain. As there have been few reports examining both mutation and deletion over the full-length of the TP53 gene, the clinical characteristics of TP53 gene abnormality have not yet been clearly established. In this study, TP53 gene mutation was observed in 7.3% of the total 412 de novo AML cases (33 mutations in 30 cases), with mutation outside the DNA binding domain in eight cases (27%). TP53 gene deletion was observed in 3.1% of 358 cases. All cases had monoallelic deletion with TP53 gene mutation on the opposite allele. Multivariate analysis demonstrated that TP53 gene mutation in the DNA binding domain and outside the DNA binding domain was an independent poor prognostic factor for overall survival and relapse-free survival among the total cohort and it is also an unfavorable prognostic factor in FLT3-ITD-negative AML cases aged 70 years or below with intermediate cytogenetic prognosis. In stratified treatment, full-length search for TP53 gene mutation is therefore very important.

Synthesis and Evaluation of Antibacterial Activity of Bottromycins.

Total synthesis of bottromycin A2 can be accomplished through a diastereoselective Mannich reaction of a chiral sulfinamide, mercury-mediated intermolecular amidination, and cyclization of a constrained tetracyclic peptide. Exploitation of this process allowed the synthesis of several novel bottromycin analogs. The antimicrobial activity of these analogs was evaluated in vitro against Gram-positive bacteria, such as methicillin resistant Staphylococcus aureus (MRSA) and vancomycin resistant enterococci (VRE). Structure-activity relationships were explored taking into consideration the unique three-dimensional structure of the compounds. Notably, one of the new analogs devoid of a methyl ester, which is known to lower the in vivo efficacy of bottromycin, exhibited antibacterial bioactivity comparable to that of vancomycin.

Total Syntheses of (+)- and (-)-Tetrapetalones A and C.

Described herein are syntheses of the naturally occurring polyketides (-)-tetrapetalones A and C and their respective enantiomers. The employed strategy involves initial assembly of a masked N-aryl tetramic acid which is advanced via a highly selective conjugate addition/intramolecular Friedel-Crafts acylation sequence to deliver a key azepine intermediate. Application of recently developed C-H activation chemistry and subsequent Heck cyclization delivers the aglycone framework in an overall 12 steps. Resolution of the aglycone via stereospecific glycosylation with an enantiopure glycosyl donor followed by separation of the derived diastereomers enables further advancement to either (+)- or (-)-tetrapetalones A and C.

Inclusive fitness analysis of cumulative cultural evolution in an island-structured population.

The success of humans on the globe is largely supported by our cultural excellence. Our culture is cumulative, meaning that it is improved from generation to generation. Previous works have revealed that two modes of learning, individual learning and social learning, play pivotal roles in the accumulation of culture. However, under the trade-off between learning and reproduction, one's investment into learning is easily exploited by those who copy the knowledge of skillful individuals and selfishly invest more efforts in reproduction. It has been shown that in order to prevent such a breakdown, the rate of vertical transmission (i.e. transmission from parents to their offspring) of culture must be unrealistically close to one. Here we investigate what if the population is spatially structured. In particular, we hypothesize that spatial structure should favor highly cumulative culture through endogenously arising high kinship. We employ Wright's island model and assume that cultural transmission occurs within a local island. Our inclusive fitness analysis reveals combined effects of direct fitness of the actor, indirect fitness through relatives in the current generation, and indirect fitness through relatives in future generations. The magnitude of those indirect benefits is measured by intergenerational coefficients of genetic relatedness. Our result suggests that the introduction of spatial structure raises the stationary level of culture in the population, but that the extent of its improvement compared with a well-mixed population is marginal unless spatial localization is extreme. Overall, our model implies that we need an alternative mechanism to explain highly cumulative culture of modern humans.